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Gene | RET |
Variant | S891A |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | RET S891A lies within the protein kinase domain of the Ret protein (UniProt.org). S891A results in constitutive phosphorylation of Ret and downstream activation of Stat3 signaling through Src, Jak1, and Jak2-dependent pathways in cell culture (PMID: 15753368). |
Associated Drug Resistance | |
Category Variants Paths |
RET mutant RET act mut RET S891A RET mutant RET S891X RET S891A |
Transcript | NM_020975.6 |
gDNA | chr10:g.43120144T>G |
cDNA | c.2671T>G |
Protein | p.S891A |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_020975 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_001406765.1 | chr10:g.43123675T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_020630.5 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_001406774.1 | chr10:g.43126731T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_001406763.1 | chr10:g.43123675T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_020630.7 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_020975.6 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_001406759.1 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_020630 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_020975.5 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_001406743.1 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_001406760.1 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
NM_001406744.1 | chr10:g.43120144T>G | c.2671T>G | p.S891A | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RET S891A | Advanced Solid Tumor | sensitive | Sorafenib | Preclinical | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited RET phosphorylation in cells expressing RET S891A in culture (PMID: 17664273). | 17664273 |
RET S891A | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited phosphorylation of Ret in transformed human cells expressing RET S891A in culture (PMID: 23526464). | 23526464 |
RET S891A | Advanced Solid Tumor | sensitive | Vandetanib | Preclinical | Actionable | In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET S891A in culture (PMID: 15184865). | 15184865 |
RET S891A | medullary thyroid carcinoma | predicted - sensitive | Vandetanib | Case Reports/Case Series | Actionable | In a clinical case study, neoadjuvant Caprelsa (vandetanib) treatment resulted in a 65% decrease in the thyroid mass and cervical lymph nodes allowing for surgical resection in a pediatric patient with medullary thyroid carcinoma harboring RET S891A (PMID: 38207224). | 38207224 |