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| Gene | PBRM1 |
| Variant | S652fs |
| Impact List | frameshift |
| Protein Effect | loss of function - predicted |
| Gene Variant Descriptions | PBRM1 S652fs results in a change in the amino acid sequence of the Pbrm1 protein beginning at aa 652 of 1689, likely resulting in premature truncation of the functional protein (UniProt.org). S652fs has not been characterized, however, due to the effects of other truncations mutations downstream of S652 (PMID: 28082722), is predicted to lead to a loss of Pbrm1 protein function. |
| Associated Drug Resistance | |
| Category Variants Paths |
PBRM1 mutant PBRM1 inact mut PBRM1 S652fs |
| Transcript | NM_018313.5 |
| gDNA | chr3:g.(52609926_52609927) |
| cDNA | c.(1954_1953) |
| Protein | p.S652fs |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_001405590.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394867.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394871.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405628.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400475.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_018313.5 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394872.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394873.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400479.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405558.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405583.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394874.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405635.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006749.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405629.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_181042.5 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405627.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400472.1 | chr3:g.(52609947_52609948) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405581.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405576.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405605.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006758.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405575.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006750 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405589.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405577.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405565.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405623.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405597.1 | chr3:g.(52609809_52609810) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405611.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405610.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400484.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405624.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405578.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405561.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_181042.4 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400504.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405603.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400501.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405557.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006765 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_018313 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405632.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405585.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405584.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394877.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001350075.2 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405588.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400474.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405609.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006757 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400473.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405567.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405630.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405593.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405639.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405640.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400500.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400470.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394876.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405634.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405641.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405579.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405556.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405563.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_018313.4 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006750.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400496.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405594.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006748.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405633.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001350075.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400490.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405631.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405612.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405559.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_047448462.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405592.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405643.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001400481.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405626.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405555.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006758 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006749 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| XM_017006748 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394869.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394875.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001394868.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| NM_001405570.1 | chr3:g.(52609926_52609927) | c.(1954_1953) | p.S652fs | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| PBRM1 inact mut | head and neck squamous cell carcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, did not correlate with improved survival in 2 separate cohorts of patients with head and neck squamous cell carcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 0.74 (p=0.631, n=31) and 0.76 (p=0.622, n=68), respectively (PMID: 32321774). | 32321774 |
| PBRM1 inact mut | clear cell renal cell carcinoma | sensitive | PRT1419 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PRT1419 inhibited proliferation and induced apoptosis in clear cell renal cell carcinoma cells lines harboring inactivating PBRM1 mutations in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 38371625). | 38371625 |
| PBRM1 inact mut | clear cell renal cell carcinoma | predicted - sensitive | PRT2527 | Preclinical - Cell culture | Actionable | In a preclinical study, PRT2527 inhibited spheroid growth in clear cell renal cell carcinoma cell lines harboring inactivating PBRM1 mutations in culture (PMID: 38371625). | 38371625 |
| PBRM1 inact mut | renal cell carcinoma | no benefit | Everolimus | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma had no difference in progression-free survival when stratified by the presence (n=6) or absence (n=22) of deleterious PBRM1 mutation when treated with Afinitor (everolimus) (PMID: 26951309). | 26951309 |
| PBRM1 inact mut | clear cell renal cell carcinoma | sensitive | Atezolizumab | Clinical Study - Cohort | Actionable | In a clinical study, renal clear cell carcinoma patients harboring PBRM1 loss-of-function mutations demonstrated improved response to immune checkpoint therapies including Opdivo (nivolumab) alone or in combination with Yervoy (ipilimumab), and Tecentriq (atezolizumab), potentially due to the distinct expression profile of immune-related genes in these patients (PMID: 29301960). | 29301960 |
| PBRM1 inact mut | melanoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, did not correlate with improved survival in 2 separate cohorts of patients with melanoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 1.70 (p=0.192, n=86) and 1.02 (p=0.939, n=192), respectively (PMID: 32321774). | 32321774 |
| PBRM1 inact mut | renal cell carcinoma | no benefit | Apitolisib | Case Reports/Case Series | Actionable | In a retrospective analysis from a Phase II clinical trial, patients with renal cell carcinoma treated with Apitolisib (GDC-0980) had no difference in progression-free survival when stratified by the presence (n=5) or absence (n=17) of deleterious PBRM1 mutations (PMID: 26951309). | 26951309 |
| PBRM1 inact mut | colorectal adenocarcinoma | unknown | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, correlated with improved survival in one cohort of patients with colorectal adenocarcinoma treated with systemic immune checkpoint inhibitors but not the other, with adjusted HRs for overall survival of 0.30 (p=0.03, n=35) and 0.56 (p=0.244, n=63), respectively (PMID: 32321774). | 32321774 |
| PBRM1 inact mut | clear cell renal cell carcinoma | sensitive | Everolimus + PRT1419 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of PRT1419 and Afinitor (everolimus) synergistically inhibited spheroid growth of clear cell renal cell carcinoma cell lines harboring inactivating PBRM1 mutations in culture (PMID: 38371625). | 38371625 |
| PBRM1 inact mut | gastroesophageal adenocarcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, did not correlate with improved survival in 2 separate cohorts of patients with gastroesophageal adenocarcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 0.70 (p=0.403, n=66) and 0.46 (p=0.071, n=59), respectively (PMID: 32321774). | 32321774 |
| PBRM1 inact mut | clear cell renal cell carcinoma | sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, renal clear cell carcinoma patients harboring PBRM1 loss-of-function mutations demonstrated improved response to immune checkpoint therapies including Opdivo (nivolumab) alone or in combination with Yervoy (ipilimumab), and Tecentriq (atezolizumab), potentially due to the distinct expression profile of immune-related genes in these patients (PMID: 29301960). | 29301960 |
| PBRM1 inact mut | clear cell renal cell carcinoma | sensitive | Cabozantinib + PRT1419 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of PRT1419 and Cometriq (Cabometyx, cabozantinib) synergistically inhibited spheroid growth of clear cell renal cell carcinoma cell lines harboring inactivating PBRM1 mutations in culture (PMID: 38371625). | 38371625 |
| PBRM1 inact mut | transitional cell carcinoma | not predictive | unspecified immune checkpoint inhibitor | Clinical Study - Cohort | Actionable | In a retrospective analysis, somatic loss-of-function mutations in the genes of the mSWI/SNF complex, including PBRM1, did not correlate with improved survival in 2 separate cohorts of patients with transitional cell carcinoma treated with systemic immune checkpoint inhibitors, with adjusted HRs for overall survival of 1.44 (p=0.34, n=56) and 0.82 (p=0.559, n=93), respectively (PMID: 32321774). | 32321774 |
| PBRM1 inact mut | kidney cancer | predicted - sensitive | GSK126 | Preclinical - Cell culture | Actionable | In a preclinical study, GSK126 inhibited growth of 3/4 tested renal cancer cell lines harboring PBRM1 inactivating mutations in culture, with inhibitor sensitivity associating with dependence on EZH2 catalytic activity (PMID: 26552009). | 26552009 |
| PBRM1 inact mut | clear cell renal cell carcinoma | sensitive | PRT1419 + Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of PRT1419 and Sutent (sunitinib) synergistically inhibited spheroid growth of clear cell renal cell carcinoma cell lines harboring inactivating PBRM1 mutations in culture (PMID: 38371625). | 38371625 |
| PBRM1 inact mut | clear cell renal cell carcinoma | sensitive | Ipilimumab + Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, renal clear cell carcinoma patients harboring PBRM1 loss-of-function mutations demonstrated improved response to immune checkpoint therapies including Opdivo (nivolumab) alone or in combination with Yervoy (ipilimumab), and Tecentriq (atezolizumab), potentially due to the distinct expression profile of immune-related genes in these patients (PMID: 29301960). | 29301960 |
| PBRM1 inact mut | clear cell renal cell carcinoma | sensitive | Pazopanib + PRT1419 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of PRT1419 and Votrient (pazopanib) synergistically inhibited spheroid growth of clear cell renal cell carcinoma cell lines harboring inactivating PBRM1 mutations in culture (PMID: 38371625). | 38371625 |
| PBRM1 mutant | clear cell renal cell carcinoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, PBRM1 truncating mutations were associated with response to Opdivo (nivolumab) with 39% (15/38) of responding patients harboring PBRM1 mutations vs 22% (16/74) of non-responders, as well as clinical benefit (p=0.0497), increased progression-free survival (HR=0.67), and overall survival (HR=0.65) in post-hoc analysis of archival samples from a Phase III clinical trial of clear cell renal cell carcinoma patients (PMID: 31486842). | 31486842 |
| PBRM1 mutant | lung non-small cell carcinoma | predicted - resistant | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, treatment with either an anti-PD-1 or anti-PD-L1 therapy resulted in a significantly shorter overall survival (p=0.0057) and progression-free survival (p=0.03) in patients with non-small cell lung cancer harboring a PBRM1 mutation compared to patients with wild-type PBRM1 (PMID: 36456601). | 36456601 |
| PBRM1 mutant | clear cell renal cell carcinoma | conflicting | Everolimus | Clinical Study - Cohort | Actionable | In a clinical study, PBRM1 truncating mutations were not associated with progression-free survival or overall survival in clear cell renal cell carcinoma patients treated with Afinitor (everolimus) (n=193) (PMID: 31486842). | 31486842 |
| PBRM1 mutant | clear cell renal cell carcinoma | conflicting | Everolimus | Phase II | Actionable | In a Phase II trial (RECORD-3), PBRM1 mutations were associated with longer first-line progression free survival (12.8 vs 5.5 months) in first-line Afinitor (everolimus)-treated clear cell renal cell carcinoma patients compared to first-line Sutent (sunitinib)-treated patients (PMID: 27751729). | 27751729 |
| PBRM1 mutant | lung non-small cell carcinoma | predicted - resistant | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, treatment with either an anti-PD-1 or anti-PD-L1 therapy resulted in a significantly shorter overall survival (p=0.0057) and progression-free survival (p=0.03) in patients with non-small cell lung cancer harboring a PBRM1 mutation compared to patients with wild-type PBRM1 (PMID: 36456601). | 36456601 |