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Gene Symbol HRAS
Synonyms C-BAS/HAS | C-H-RAS | C-HA-RAS1 | CTLO | H-RASIDX | HAMSV | HRAS1 | p21ras | RASH1
Gene Description HRAS, HRas proto-oncogene, GTPase, is a member of the small GTPase family that upon activation by growth factors stimulates multiple downstream pathways such as RAF and PI3K to promote cell proliferation and survival (PMID: 21779504, PMID: 32241873). HRAS activating mutations are commonly found in tumors, including dermatological, head and neck, thyroid, kidney, bladder cancers (PMID: 29524560), squamous cell papilloma (PMID: 31960612), and breast adenomyoepitheliomas (PMID: 31887226).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
3265 11 11p15.5 NM_005343 Oncogene (PMID: 30606230)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A11D missense unknown HRAS A11D does not lie within any known functional domains of the Hras protein (UniProt.org). A11D has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jan 2024).
A11S missense unknown HRAS A11S does not lie within any known functional domains of the Hras protein (UniProt.org). A11S has been identified in the scientific literature (PMID: 22683711, PMID: 29210482), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
A130T missense unknown HRAS A130T does not lie within any known functional domains of the Hras protein (UniProt.org). A130T has been identified in the scientific literature (PMID: 30348504), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
A134S missense unknown HRAS A134S does not lie within any known functional domains of the Hras protein (UniProt.org). A134S has been identified in sequencing studies (PMID: 26870252), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
A134T missense unknown HRAS A134T does not lie within any known functional domains of the Hras protein (UniProt.org). A134T has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
A146T missense gain of function HRAS A146T lies within the SAK motif of the Hras protein (PMID: 24224811). A146T does not affect Hras intrinsic GTPase activity, but results in increased nucleotide exchange rates, which leads to increase GTP-bound Hras, activation of downstream signaling, and senescence of cultured cells (PMID: 24224811, PMID: 21850009).
A146V missense gain of function HRAS A146V lies within the SAK motif of the Hras protein (PMID: 24224811). A146V does not affect Hras intrinsic GTPase activity, but results in increased nucleotide exchange rates, which leads to increase GTP-bound Hras, activation of downstream signaling, and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 3043178).
A59D missense unknown HRAS A59D lies within a GTP binding region of the Hras protein (UniProt.org). A59D has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
A59I missense loss of function HRAS A59I lies within a GTP binding region of the Hras protein (UniProt.org). A59I demonstrates nucleotide affinity and exchange rate similar to wild-type protein, but results in reduced GTPase activity and decreased transforming potential in culture (PMID: 3043178).
A59Rfs*32 frameshift loss of function - predicted HRAS A59Rfs*32 indicates a shift in the reading frame starting at amino acid 59 and terminating 32 residues downstream causing a premature truncation of the 189 amino acid Hras protein (UniProt.org). Due to the loss of the GTP binding domain (UniProt.org), A59Rfs*32 is predicted to lead to a loss of Hras protein function resulting in inactivation of downstream signaling.
A59T missense gain of function HRAS A59T lies within the GTP binding domain of the Hras protein (UniProt.org). A59T does not affect Hras GTPase activity, but increases nucleotide exchange rate, resulting in increase GTP-bound Hras and transformation of cultured cells (PMID: 21779495, PMID: 3004741).
A66E missense no effect - predicted HRAS A66E does not lie within any known functional domains of the Hras protein (UniProt.org). A66E results in intrinsic and GAP-stimulated GTPase activity comparable to wild-type Hras in in vitro assays (PMID: 1730690), and therefore, is predicted to have no effect on Hras protein function.
A66G missense no effect - predicted HRAS A66G does not lie within any known functional domains of the Hras protein (UniProt.org). A66G results in intrinsic and GAP-stimulated GTPase activity comparable to wild-type Hras in in vitro assays (PMID: 1730690), and therefore, is predicted to have no effect on Hras protein function.
A66R missense no effect - predicted HRAS A66R does not lie within any known functional domains of the Hras protein (UniProt.org). A66R results in intrinsic and GAP-stimulated GTPase activity comparable to wild-type Hras in in vitro assays (PMID: 1730690), and therefore, is predicted to have no effect on Hras protein function.
A66T missense unknown HRAS A66T does not lie within any known functional domains of the Hras protein (UniProt.org). A66T has been identified in sequencing studies (PMID: 22722201), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
A66W missense no effect - predicted HRAS A66W does not lie within any known functional domains of the Hras protein (UniProt.org). A66W results in intrinsic and GAP-stimulated GTPase activity comparable to wild-type Hras in in vitro assays (PMID: 1730690), and therefore, is predicted to have no effect on Hras protein function.
act mut unknown unknown HRAS act mut indicates that the variant results in activation of HRAS downstream signaling. The mechanism causing the activation can include either loss of GTP hydrolysis activity (loss of function) or increased nucleotide exchange rate (gain of function).
amp none no effect HRAS amplification indicates an increased number of copies of the HRAS gene. However, the mechanism causing the increase is unspecified.
D33N missense loss of function HRAS D33N lies within the effector region of the Hras protein (UniProt.org). D33N demonstrates decreased binding affinity for effector protein Raf compared to wild-type Hras, and is not transforming in cell culture (PMID: 28686159, PMID: 8035810).
D47E missense unknown HRAS D47E does not lie within any known functional domains of the Hras protein (UniProt.org). D47E has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
E143K missense unknown HRAS E143K does not lie within any known functional domains of the Hras protein (UniProt.org). E143K has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
E162G missense unknown HRAS E162G does not lie within any known functional domains of the Hras protein (UniProt.org). E162G has not been characterized and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
E162K missense unknown HRAS E162K does not lie within any known functional domains of the Hras protein (UniProt.org). E162K has been identified in the scientific literature (PMID: 22932669), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
E62A missense no effect - predicted HRAS E62A lies within the GTP binding domain of the Hras protein (PMID: 21779495). E62A results in intrinsic and GAP-stimulated GTPase activity comparable to wild-type Hras in in vitro assays (PMID: 1730690), and therefore, is predicted to have no effect on Hras protein function.
E62G missense unknown HRAS E62G lies within the GTP binding domain of the Hras protein (PMID: 21779495). E62G has been identified in the scientific literature (PMID: 19628422, PMID: 35062725), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
E91K missense unknown HRAS E91K does not lie within any known functional domains of the Hras protein (UniProt.org). E91K has not been characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
F82L missense unknown HRAS F82L does not lie within any known functional domains of the Hras protein (UniProt.org). F82L has been identified in the scientific literature (PMID: 28939558, PMID: 25360634), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
G10S missense unknown HRAS G10S does not lie within any known functional domains of the Hras protein (UniProt.org). G10S has been identified in sequencing studies (PMID: 27713118), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jan 2024).
G12A missense loss of function HRAS G12A does not lie within any known functional domains of the Hras protein (UniProt.org). G12A results in decreased Hras GTPase activity, loss of sensitivity to GTPase-activating proteins, leading to transformation of cells in culture (PMID: 24224811, PMID: 6092966).
G12C missense loss of function HRAS G12C does not lie within any known functional domains of the Hras protein (UniProt.org). G12C results in decreased Hras GTPase activity, loss of sensitivity to GTPase-activating proteins, thus leads to transformation of cells in culture (PMID: 24224811, PMID: 6092966).
G12D missense loss of function HRAS G12D does not lie within any known functional domains of the Hras protein (UniProt.org). G12D results in decreased Hras GTPase activity, loss of sensitivity to GTPase-activating proteins, thus leads to transformation of cells in culture (PMID: 24224811, PMID: 6092966).
G12E missense loss of function HRAS G12E does not lie within any known functional domains of the Hras protein (UniProt.org). G12E results in decreased Hras GTPase activity and loss of response to GTPase-activating proteins, and is transforming in cultured cells (PMID: 24224811, PMID: 6092966).
G12F missense loss of function - predicted HRAS G12F does not lie within any known functional domains of the Hras protein (UniProt.org). G12F is transforming in culture (PMID: 6092966), and is predicted to result in a loss of Hras protein function based on the effect of KRAS G12F, which results in decreased Kras GTPase activity and activation of downstream Mapk signaling (PMID: 11668624).
G12H missense loss of function - predicted HRAS G12H does not lie within any known functional domains of the Hras protein (UniProt.org). G12H is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12I missense loss of function - predicted HRAS G12I does not lie within any known functional domains of the Hras protein (UniProt.org). G12I is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12K missense loss of function - predicted HRAS G12K does not lie within any known functional domains of the Hras protein (UniProt.org). G12K is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12L missense loss of function - predicted HRAS G12L does not lie within any known functional domains of the Hras protein (UniProt.org). G12L is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12M missense loss of function - predicted HRAS G12M does not lie within any known functional domains of the Hras protein (UniProt.org). G12M is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12N missense loss of function - predicted HRAS G12N does not lie within any known functional domains of the Hras protein (UniProt.org). G12N is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12Q missense loss of function - predicted HRAS G12Q does not lie within any known functional domains of the Hras protein (UniProt.org). G12Q is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12R missense loss of function HRAS G12R does not lie within any known functional domains of the Hras protein (UniProt.org). G12R results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3042780, PMID: 6092966).
G12S missense loss of function HRAS G12S does not lie within any known functional domains of the Hras protein (UniProt.org). G12S results in decreased Hras GTPase activity, loss of response to GTPase-activating proteins, leading to activation of downstream signaling pathways and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 6330729).
G12T missense loss of function - predicted HRAS G12T does not lie within any known functional domains of the Hras protein (UniProt.org). G12T is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12V missense loss of function HRAS G12V does not lie within any known functional domains of the Hras protein (UniProt.org). G12V results in decreased Hras GTPase activity, loss of response to GTPase-activating proteins, leading to activation of downstream signaling pathways, and transformation of cultured cells (PMID: 24224811, PMID: 21850009, PMID: 6330729).
G12W missense loss of function - predicted HRAS G12W does not lie within any known functional domains of the Hras protein (UniProt.org). G12W is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G12X missense unknown HRAS G12X indicates any HRAS missense mutation that results in replacement of the glycine (G) at amino acid 12 by a different amino acid. HRAS G12 mutations are hotspot mutations that often result in decreased Hras GTPase activity, leading to activation of downstream signaling and transformation of cultured cells (PMID: 6092966, PMID: 24224811, PMID: 26985062).
G12Y missense loss of function - predicted HRAS G12Y does not lie within any known functional domains of the Hras protein (UniProt.org). G12Y is transforming in cultured cells (PMID: 6092966), and can be predicted to lead to a loss of Hras protein function and activation of downstream signaling based on the effects of other HRAS G12 mutations.
G13C missense loss of function HRAS G13C is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13C results in decreased Hras GTPase activity and loss of response to GTPase-activating proteins, leading to activation of downstream signaling and cell senescence in culture (PMID: 24224811, PMID: 21850009).
G13D missense loss of function HRAS G13D is hotspot mutation that lies within the GTP nucleotide binding region of the Hras protein (UniProt.org). G13D results in decreased Hras GTPase activity and loss of response to GTPase-activating proteins, leading to activation of downstream signaling and senescence in cell culture (PMID: 24224811, PMID: 21850009).
G13dup duplication unknown HRAS G13dup indicates the insertion of the duplicate amino acid, glycine (G)-13, in a GTP-binding region of the Hras protein (UniProt.org). G13dup has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
G13I missense unknown HRAS G13I is hotspot mutation that lies within the GTP-binding region of the Hras protein (UniProt.org). G13I has been identified in the scientific literature (PMID: 26974156, PMID: 22817889), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
G13N missense unknown HRAS G13N lies within the GTP nucleotide binding region of the Hras protein (UniProt.org). G13N has been identified in sequencing studies (PMID: 34424952), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
G13R missense loss of function - predicted HRAS G13R is hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13R results in activation of Mapk and Pi3k signaling, increased cell proliferation in culture (PMID: 22683711), and is predicted to lead to a loss of Hras protein function based on the effects of other HRAS G13 mutations.
G13S missense gain of function HRAS G13S is hotspot mutation that lies within the GTP-binding domain of the Hras protein (UniProt.org). G13S results in increased Hras GTPase activity, loss of response to GTPase-activating proteins, leading to transformation in Xenopus oocytes (PMID: 8430333).
G13T missense gain of function HRAS G13T is hotspot mutation that lies within the GTP-binding domain of the Hras protein (UniProt.org). G13T results in increased Hras GTPase activity and loss of response to GTPase-activating proteins, leading to transformation in Xenopus oocytes (PMID: 8430333).
G13V missense loss of function HRAS G13V is a hotspot mutation that lies within the GTP binding domain of the Hras protein (UniProt.org). G13V does not affect Hras GTPase activity, but results in a loss of response to GTPase-activating proteins, leading to increased GTP-bound Hras in culture (PMID: 24224811).
G13X missense unknown HRAS G13X indicates any HRAS missense mutation that results in replacement of the glycine (G) at amino acid 13 by a different amino acid. HRAS G13 mutations are hotspot mutations that often result in decreased Hras GTPase activity, leading to activation of downstream signaling and transformation of cultured cells (PMID: 8430333, PMID: 21850009, PMID: 24224811, PMID: 26985062).
G151E missense unknown HRAS G151E does not lie within any known functional domains of the Hras protein (UniProt.org). G151E has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
G15S missense unknown HRAS G15S lies within a GTP-binding region of the Hras protein (UniProt.org). G15S has been identified in sequencing studies (PMID: 29844865, PMID: 9528840), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
G48R missense no effect - predicted HRAS G48R does not lie within any known functional domains of the Hras protein (UniProt.org). G48R demonstrates GTP affinity and GTP hydrolysis activity similar to wild-type Hras, and enhances effector recruitment in combination with HRAS G12V in culture (PMID: 26274561), and therefore, is predicted to have no effect on Hras protein function.
inact mut unknown loss of function HRAS inact mut indicates that the variant results in failure to activate HRAS downstream signaling. However, the specific amino acid change has not been identified.
K117E missense loss of function HRAS K117E lies within the GTP binding domain of the Hras protein (UniProt.org). K117E confers a loss of function on Hras protein as indicated by increased GTP-bound Hras, activation of downstream signaling, and transformation of cultured cells (PMID: 12569357).
K117N missense loss of function HRAS K117N lies within the GTP binding domain of the Hras protein (UniProt.org). K117N results in decreased nucleotide binding affinity and activation of Hras in culture (PMID: 24247240).
K117R missense gain of function HRAS K117R lies within the GTP binding region of the Hras protein (UniProt.org). K117R does not affect Hras intrinsic GTPase activity, but increases nucleotide exchange rates, resulting in increased GTP-boud Hras, activation of downstream signaling, and cell senescence in culture (PMID: 24224811, PMID: 17979197, PMID: 21850009).
L120V missense unknown HRAS L120V does not lie within any known functional domains of the Hras protein (UniProt.org). L120V has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
L133R missense unknown HRAS L133R does not lie within any known functional domains of the Hras protein (UniProt.org). L133R has been identified in sequencing studies (PMID: 25275298), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2023).
mutant unknown unknown HRAS mutant indicates an unspecified mutation in the HRAS gene.
N116H missense gain of function HRAS N116H lies within a nucleotide-binding region of the Hras protein (UniProt.org). N116H results in increased nucleotide exchange rate in in vitro assays, and is transforming in cell culture (PMID: 3043178, PMID: 1549350).
N116I missense loss of function HRAS N116I lies within a nucleotide-binding region of the Hras protein (UniProt.org). N116I results in a loss of intrinsic and GEF-stimulated GTPase activity, and is transforming in cell culture (PMID: 3487832, PMID: 8227029).
N116Q missense no effect - predicted HRAS N116Q lies within a nucleotide-binding region of the Hras protein (UniProt.org). N116I results in GTPase activity similar to wild-type Hras and is not transforming in cell culture (PMID: 3487832), and therefore, is predicted to have no effect on Hras protein function.
N26S missense unknown HRAS N26S does not lie within any known functional domains of the Hras protein (UniProt.org). N26S has been identified in sequencing studies (PMID: 28229982, PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
over exp none no effect HRAS over exp indicates an over expression of the Hras protein and/or mRNA. However, the mechanism causing the over expression is unspecified.
P174S missense unknown HRAS P174S lies within the hypervariable region of the Hras protein (UniProt.org). P174S has been identified in sequencing studies (PMID: 26080840), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
positive unknown unknown HRAS positive indicates the presence of the HRAS gene, mRNA, and/or protein.
Q61A missense loss of function HRAS Q61A does not lie within any known functional domains of the Hras protein (UniProt.org). Q61A results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61C missense loss of function HRAS Q61C does not lie within any known functional domains of the Hras protein (UniProt.org). Q61C results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61E missense loss of function HRAS Q61E does not lie within any known functional domains of the Hras protein (UniProt.org). Q61E results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61F missense loss of function HRAS Q61F does not lie within any known functional domains of the Hras protein (UniProt.org). Q61F results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61G missense loss of function HRAS Q61G does not lie within any known functional domains of the Hras protein (UniProt.org). Q61G results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61H missense loss of function HRAS Q61H does not lie within any known functional domains of the Hras protein (UniProt.org). Q61H results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61I missense loss of function HRAS Q61I does not lie within any known functional domains of the Hras protein (UniProt.org). Q61I results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61K missense loss of function HRAS Q61K does not lie within any known functional domains of the Hras protein (UniProt.org). Q61K results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61L missense loss of function HRAS Q61L does not lie within any known functional domains of the Hras protein (UniProt.org). Q61L results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 23487764, PMID: 3510078).
Q61M missense loss of function HRAS Q61M does not lie within any known functional domains of the Hras protein (UniProt.org). Q61M results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61N missense loss of function HRAS Q61N does not lie within any known functional domains of the Hras protein (UniProt.org). Q61N results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61P missense loss of function HRAS Q61P does not lie within any known functional domains of the Hras protein (UniProt.org). Q61P results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61R missense loss of function HRAS Q61R does not lie within any known functional domains of the Hras protein (UniProt.org). Q61R results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61T missense loss of function HRAS Q61T does not lie within any known functional domains of the Hras protein (UniProt.org). Q61T results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61V missense loss of function HRAS Q61V does not lie within any known functional domains of the Hras protein (UniProt.org). Q61V results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61W missense loss of function HRAS Q61W does not lie within any known functional domains of the Hras protein (UniProt.org). Q61W results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q61X missense unknown HRAS Q61X indicates any HRAS missense mutation that results in replacement of the glutamine (Q) at amino acid 61 by a different amino acid. HRAS Q61 mutations are hotspot mutations that often result in decreased Hras GTPase activity, leading to activation of downstream signaling and transformation of cultured cells (PMID: 3510078, PMID: 26985062).
Q61Y missense loss of function HRAS Q61Y does not lie within any known functional domains of the Hras protein (UniProt.org). Q61Y results in decreased Hras GTPase activity and leads to transformation of cells in culture (PMID: 3510078).
Q95H missense unknown HRAS Q95H does not lie within any known functional domains of the Hras protein (UniProt.org). Q95H has been identified in the scientific literature (PMID: 37339170), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jan 2024)
R123C missense unknown HRAS R123C does not lie within any known functional domains of the Hras protein (UniProt.org). R123C fails to interact with oncogenic Kras, reduce Erk phosphorylation, and decrease cell proliferation in Kras-mutant cells in culture (PMID: 36635501), but has not been fully biochemically characterized and therefore, its effect on Hras protein function is unknown.
R123H missense unknown HRAS R123H does not lie within any known functional domains of the Hras protein (UniProt.org). R123H has been identified in sequencing studies (PMID: 25303977, PMID: 36089135), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
R128L missense unknown HRAS R128L does not lie within any known functional domains of the Hras protein (UniProt.org). R128L has been identified in sequencing studies (PMID: 22941189), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
R128W missense unknown HRAS R128W does not lie within any known functional domains of the Hras protein (UniProt.org). R128W has been identified in sequencing studies (PMID: 27499925), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
R135A missense unknown HRAS R135A does not lie within any known functional domains of the Hras protein (UniProt.org). R135A results in impaired GTP-HRAS downstream signaling when combined with R128A (PMID: 18273062), and is associated with resistance to NS1 (PMID: 27820802), but has not been fully biochemically characterized and therefore, its effect on Hras protein function is unknown. Y
R135K missense unknown HRAS R135K does not lie within any known functional domains of the Hras protein (UniProt.org). R135K is predicted to disrupt the allosteric interaction within Hras by molecular dynamics simulation (PMID: 29072601), and results in decreased NS1 binding in the context of HRAS G12C, resulting in resistance to NS1, in cultured cells (PMID: 27820802) and leads to loss of binding to NS1 in cultured cells in another study (PMID: 36252024), but has not been fully biochemically characterized and therefore, its effect on Hras protein function is unknown. Y
R149Gfs*23 frameshift loss of function - predicted HRAS R149Gfs*23 indicates a shift in the reading frame starting at amino acid 149 and terminating 23 residues downstream causing a premature truncation of the 189 amino acid Hras protein (UniProt.org). R149Gfs*23 has not been biochemically characterized however, due to the loss of the CAXX motif (PMID: 6087162, PMID: 21924373), is predicted to lead to a loss of Hras protein function resulting in inactivation of downstream signaling.
R73C missense unknown HRAS R73C does not lie within any known functional domains of the Hras protein (UniProt.org). R73C has been identified in sequencing studies (PMID: 22185227, PMID: 15861495), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Nov 2023).
R73H missense unknown HRAS R73H does not lie within any known functional domains of the Hras protein (UniProt.org). R73H has been identified in sequencing studies (PMID: 31604779), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
S106W missense unknown HRAS S106W does not lie within any known functional domains of the Hras protein (UniProt.org). S106W has not been characterized and therefore, its effect on Hras protein function is unknown (PubMed, Feb 2024).
T58I missense loss of function HRAS T58I does not lie within any known functional domains of the Hras protein (UniProt.org). T58I confers a loss of function on the Hras protein as indicated by decreased GTP hydrolysis and binding to GEF proteins, leading to constitutive activation of Hras signaling in culture (PMID: 26888048).
V14M missense gain of function - predicted HRAS V14M lies within the GTP binding domain of the Hras protein (UniProt.org). V14M results in increased nucleotide binding affinity and accelerated nucleotide exchange rate in in vitro assays, but demonstrates transformation potential similar to wild-type protein in culture (PMID: 3043178), and therefore, is predicted to lead to a gain of Hras protein function.
V29Cfs*19 frameshift loss of function - predicted HRAS V29Cfs*19 indicates a shift in the reading frame starting at amino acid 29 and terminating 19 residues downstream causing a premature truncation of the 189 amino acid Hras protein (UniProt.org). Due to the loss of the GTP binding domain (UniProt.org), V29Cfs*19 is predicted to lead to a loss of Hras protein function resulting in inactivation of downstream signaling.
V81M missense unknown HRAS V81M does not lie within any known functional domains of the Hras protein (UniProt.org). V81M has been identified in sequencing studies (PMID: 27612322, PMID: 24997986, PMID: 14616967), but has not been biochemically characterized and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
wild-type none no effect Wild-type HRAS indicates that no mutation has been detected within the HRAS gene.
Y157F missense unknown HRAS Y157F does not lie within any known functional domains of the Hras protein (UniProt.org). Y157F has not been characterized in the scientific literature and therefore, its effect on Hras protein function is unknown (PubMed, Jun 2024).
Y32* nonsense loss of function - predicted HRAS Y32* results in the premature truncation of the Hras protein at amino acid 32 of 189 (UniProt.org). Due to the loss of the GTP binding domain of Hras (UniProt.org), Y32* is predicted to lead to a loss of Hras protein function resulting in inactivation of downstream signaling.
Y32S missense unknown HRAS Y32S lies within the switch I region of the Hras protein (PMID: 11333268). Y32S results in a moderate increase of nucleotide exchange rate, but decreased binding to Sos and reduced sensitivity to Sos-mediated nucleotide exchange (PMID: 11333268), and therefore, its effect on Hras protein function is unknown.
Y40A missense gain of function - predicted HRAS Y40A lies within the switch I region of the Hras protein (PMID: 11333268). Y40A results in decreased binding to Sos1 but responds to Sos-mediated nucleotide exchange, and demonstrates increased intrinsic GDP/GTP exchange rate in in vitro assays, and therefore, is predicted to lead to a gain of Hras protein function (PMID: 11333268).
Y64D missense loss of function HRAS Y64D does not lie within any known functional domains of the Hras protein (UniProt.org). Y64D results in a loss of intrinsic and GAP-stimulated GTPase activity of Hras in in vitro assays and fails to transform cells in culture (PMID: 1730690).
Y64E missense loss of function HRAS Y64E does not lie within any known functional domains of the Hras protein (UniProt.org). Y64E results in a loss of intrinsic and GAP-stimulated GTPase activity of Hras in in vitro assays and fails to transform cells in culture (PMID: 1730690).
Y64F missense unknown HRAS Y64F does not lie within any known functional domains of the Hras protein (UniProt.org). Y64F results in slightly decreased intrinsic and GAP-stimulated GTPase activity in in vitro assays, but maintains transforming activity in cultured cells (PMID: 1730690), and therefore, its effect on Hras protein function is unknown.
Y64G missense loss of function HRAS Y64G does not lie within any known functional domains of the Hras protein (UniProt.org). Y64G results in a loss of intrinsic and GAP-stimulated GTPase activity of Hras in in vitro assays and fails to transform cells in culture (PMID: 1730690).
Y64L missense unknown HRAS Y64L does not lie within any known functional domains of the Hras protein (UniProt.org). Y64L demonstrates intrinsic GTPase activity comparable to wild-type protein, but results in decreased response to GAP stimulation in in vitro assays, and maintains transforming activity in cultured cells (PMID: 1730690), and therefore, its effect on Hras protein function is unknown.
Y64Q missense loss of function HRAS Y64Q does not lie within any known functional domains of the Hras protein (UniProt.org). Y64Q results in a loss of intrinsic and GAP-stimulated GTPase activity of Hras in in vitro assays and fails to transform cells in culture (PMID: 1730690).
Y64W missense loss of function HRAS Y64W does not lie within any known functional domains of the Hras protein (UniProt.org). Y64W results in a loss of intrinsic and GAP-stimulated GTPase activity of Hras in in vitro assays and fails to transform cells in culture (PMID: 1730690).