PBRM1 (Protein polybromo-1) variants and mutations
PBRM1 (also known as Protein polybromo-1) is a human protein-coding gene encoding a protein polybromo-1 protein. It helps PBAF chromatin-remodeling complexes recognize modified nucleosomes and regulate transcription in response to cellular signals. Somatic loss-of-function variants are especially common in clear-cell renal cell carcinoma and support a major tumor-suppressor role. This analysis covers 1,716 PBRM1 variants and mutations. Of these, 43% have computational variant effect predictions. Disease context includes clear cell renal carcinoma, renal cell carcinoma, and cholangiocarcinoma. Example PBRM1 variants include K4Q, R6K, and R7I.
Variant analysis overview
- Gene: PBRM1
- Protein: Protein polybromo-1
- UniProt accession: Q86U86
- Organism: Homo sapiens
- Variants analyzed: 1716
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,328 unspecified-consequence records; 95 synonymous variants; 260 missense variants; 8 stop-gained variants; 14 frameshift variants; 6 in-frame deletions; 2 splice-region variants; 3 substitution
- Prediction scores: 739 variants have prediction scores (43% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: clear cell renal carcinoma, renal cell carcinoma, cholangiocarcinoma, melanoma, cutaneous melanoma, pleural mesothelioma, papillary renal cell carcinoma, neurodegenerative disease, kidney neoplasm, hemangioblastoma, hepatobiliary neoplasm, carcinoma of liver and intrahepatic biliary tract.
Protein structure and variant hotspots
- Protein features: 8 domains; 23 post-translational modification sites.
- Structural context: 816 variants have structural context.
- PTM context: 13 variants overlap post-translational modification sites.
- Experimental data: 62 protein positions have experimental scores. Source: PBRM1 High mobility group box domain domainome 1.0.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable PBRM1 variants
Examples include K4Q, R6K, R7I, A8T, T9A, S10T, P11L, S12F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- K4Q (p.Lys4Gln), cosmic curated COSV10439
- R6K (p.Arg6Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R7I (p.Arg7Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A8T (p.Ala8Thr), cosmic curated COSV56307, TOPMed rs1169692229, gnomAD rs1169692229, REVEL 0.03, CADD 21.30
- T9A (p.Thr9Ala), cosmic curated COSV56315, REVEL 0.15, CADD 25.60
- S10T (p.Ser10Thr), cosmic curated COSV56304, Ensembl rs2154067391
- P11L (p.Pro11Leu), cosmic curated COSV10516, Ensembl rs2154067299
- S12F (p.Ser12Phe), cosmic curated COSV56263, Ensembl rs2154067256
- S14N (p.Ser14Asn), cosmic curated COSV10963, ExAC rs757435999, TOPMed rs757435999, gnomAD rs757435999, REVEL 0.13, CADD 23.50
- V15G (p.Val15Gly), NCI-TCGA TCGA novel, REVEL 0.09, CADD 23.60, Variant assessed as somatic; high impact.
- G17R (p.Gly17Arg), rs764436452, NCI-TCGA Cosmic COSV9904, cosmic curated COSV99046, ExAC rs764436452, REVEL 0.32, CADD 24.30, Variant assessed as somatic; moderate impact.
- G17V (p.Gly17Val), cosmic curated COSV99967, Ensembl rs2154066996
- D20G (p.Asp20Gly), NCI-TCGA Cosmic COSV5627, cosmic curated COSV56270, Ensembl rs2154066906, Variant assessed as somatic; moderate impact.
- D20N (p.Asp20Asn), cosmic curated COSV56271, Ensembl rs2154066920
- G22W (p.Gly22Trp), cosmic curated COSV99971
- S25F (p.Ser25Phe), cosmic curated COSV10963, Ensembl rs2154066607
- R33G (p.Arg33Gly), cosmic curated COSV56282, TOPMed rs1296531217, gnomAD rs1296531217, REVEL 0.21, CADD 26.40
- K34* (p.Lys34Ter), cosmic curated COSV56264, Ensembl rs2154066104
- R35K (p.Arg35Lys), cosmic curated COSV56299, Ensembl rs2154066052
- L38F (p.Leu38Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L41I (p.Leu41Ile), cosmic curated COSV99971, TOPMed rs1317265743, gnomAD rs1317265743, REVEL 0.04, CADD 19.10
- P42L (p.Pro42Leu), NCI-TCGA Cosmic COSV5626, cosmic curated COSV56269, Ensembl rs2154065717, Variant assessed as somatic; moderate impact.
- V44C (p.Val44Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A48D (p.Ala48Asp), cosmic curated COSV56312, REVEL 0.25, CADD 24.30
- A48V (p.Ala48Val), cosmic curated COSV99971, gnomAD rs866121544, REVEL 0.22, CADD 28.60
- V49L (p.Val49Leu), rs542945393, cosmic curated COSV56302, ExAC rs542945393, gnomAD rs542945393, AlphaMissense 0.92, MetaLR 0.06, Benign
- C50* (p.Cys50Ter), cosmic curated COSV56280, Ensembl rs2154058542, CADD 34.00
- C50A (p.Cys50Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- H51L (p.His51Leu), cosmic curated COSV10516, Ensembl rs2154058502
- E52* (p.Glu52Ter), cosmic curated COSV56287, Ensembl rs2097152366, CADD 36.00
- Y54* (p.Tyr54Ter), cosmic curated COSV56278
- Y54C (p.Tyr54Cys), NCI-TCGA Cosmic COSV5627, cosmic curated COSV56274, Ensembl rs2154058313, REVEL 0.58, CADD 27.20, Variant assessed as somatic; moderate impact.
- T56A (p.Thr56Ala), rs923060956, UniProt VAR 064654, Ensembl rs923060956, AlphaMissense 0.34, MetaLR 0.04, Benign
- I57M (p.Ile57Met), cosmic curated COSV56288, Ensembl rs2154058109
- I57V (p.Ile57Val), cosmic curated COSV56310
- R58* (p.Arg58Ter), cosmic curated COSV56265, Ensembl rs2154058091, CADD 36.00
- R58Q (p.Arg58Gln), rs1402616012, NCI-TCGA Cosmic COSV9996, cosmic curated COSV99968, gnomAD rs1402616012, REVEL 0.33, CADD 25.10, Variant assessed as somatic; moderate impact.
- D59M (p.Asp59Met), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Y60* (p.Tyr60Ter), cosmic curated COSV56280
- Y60D (p.Tyr60Asp), cosmic curated COSV56314
- K61* (p.Lys61Ter), cosmic curated COSV10516, ESP rs373517762, ExAC rs373517762, TOPMed rs373517762
- K61T (p.Lys61Thr), NCI-TCGA Cosmic COSV5628, cosmic curated COSV56287, Variant assessed as somatic; moderate impact.
- D62Y (p.Asp62Tyr), cosmic curated COSV56297, Ensembl rs2154057838
- E63* (p.Glu63Ter), cosmic curated COSV99969
- Q64* (p.Gln64Ter), cosmic curated COSV56281
- G65D (p.Gly65Asp), NCI-TCGA TCGA novel, Ensembl rs2154057651, REVEL 0.47, CADD 26.10, Variant assessed as somatic; moderate impact.
- R66G (p.Arg66Gly), rs368888772, UniProt VAR 064656, ESP rs368888772, ExAC rs368888772, REVEL 0.45, CADD 26.60, Benign
- R66K (p.Arg66Lys), cosmic curated COSV56270, Ensembl rs2154057580
- L68F (p.Leu68Phe), NCI-TCGA Cosmic COSV9996, cosmic curated COSV99968, Ensembl rs2154057468, Variant assessed as somatic; moderate impact.
- C69* (p.Cys69Ter), cosmic curated COSV56265, TOPMed rs2097151478, cosmic curated COSV56278
- C69L (p.Cys69Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E70D (p.Glu70Asp), rs934149529, []
- F72* (p.Phe72Ter), cosmic curated COSV56292
- R74G (p.Arg74Gly), cosmic curated COSV10439
- R74S (p.Arg74Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A75V (p.Ala75Val), NCI-TCGA Cosmic COSV5626, cosmic curated COSV56261, Ensembl rs2154057083, Variant assessed as somatic; moderate impact.
- R78* (p.Arg78Ter), NCI-TCGA Cosmic COSV5627, cosmic curated COSV56276, Ensembl rs2154056983, Variant assessed as somatic; high impact.
- R78Q (p.Arg78Gln), cosmic curated COSV56314, ExAC rs755035966, TOPMed rs755035966, gnomAD rs755035966, REVEL 0.32, CADD 29.20
- R79* (p.Arg79Ter), cosmic curated COSV56261, Ensembl rs2154056957
- R79I (p.Arg79Ile), cosmic curated COSV56265
- N80Y (p.Asn80Tyr), cosmic curated COSV56287
- Q81* (p.Gln81Ter), cosmic curated COSV56304
- Y85* (p.Tyr85Ter), NCI-TCGA Cosmic COSV5628, cosmic curated COSV56283, Variant assessed as somatic; high impact.
- Q90* (p.Gln90Ter), NCI-TCGA Cosmic COSV5630, cosmic curated COSV56300, Ensembl rs2153986131, Variant assessed as somatic; high impact.
- Q90E (p.Gln90Glu), UniProt VAR 064657, REVEL 0.22, CADD 23.20, Uncertain significance
- D93N (p.Asp93Asn), cosmic curated COSV56290
- L94F (p.Leu94Phe), cosmic curated COSV56267
- K96* (p.Lys96Ter), NCI-TCGA Cosmic COSV5628, NCI-TCGA Cosmic COSV5629, cosmic curated COSV56297, Variant assessed as somatic; high impact.
- Q98* (p.Gln98Ter), NCI-TCGA Cosmic COSV5627, cosmic curated COSV56273, Variant assessed as somatic; high impact.
- Q99* (p.Gln99Ter), NCI-TCGA Cosmic COSV5626, NCI-TCGA Cosmic COSV9997, cosmic curated COSV99970, Variant assessed as somatic; high impact.
- K100* (p.Lys100Ter), cosmic curated COSV56306
- K100E (p.Lys100Glu), cosmic curated COSV56290
- L101Q (p.Leu101Gln), cosmic curated COSV56289
- K102E (p.Lys102Glu), cosmic curated COSV56302
- M103I (p.Met103Ile), cosmic curated COSV10881
- E104* (p.Glu104Ter), cosmic curated COSV56277
- E105* (p.Glu105Ter), cosmic curated COSV56260
- E105Q (p.Glu105Gln), NCI-TCGA Cosmic COSV5626, NCI-TCGA Cosmic COSV9996, cosmic curated COSV99968, REVEL 0.19, CADD 25.10, Variant assessed as somatic; moderate impact.
- Y106C (p.Tyr106Cys), cosmic curated COSV56315
- D107G (p.Asp107Gly), cosmic curated COSV56282
- D115N (p.Asp115Asn), cosmic curated COSV56288
- D115S (p.Asp115Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- D115V (p.Asp115Val), cosmic curated COSV56285
- D115Y (p.Asp115Tyr), cosmic curated COSV56287
- F116I (p.Phe116Ile), cosmic curated COSV10461
- F116S (p.Phe116Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L119H (p.Leu119His), NCI-TCGA Cosmic COSV5626, NCI-TCGA Cosmic COSV5627, Variant assessed as somatic; moderate impact.
- L119P (p.Leu119Pro), cosmic curated COSV56263
- F120* (p.Phe120Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- N121* (p.Asn121Ter), cosmic curated COSV56267
- N121Y (p.Asn121Tyr), cosmic curated COSV56285
- N122K (p.Asn122Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- N122Y (p.Asn122Tyr), cosmic curated COSV56285
- S125F (p.Ser125Phe), cosmic curated COSV56287
- S125P (p.Ser125Pro), cosmic curated COSV56300, REVEL 0.14, CADD 23.40
- Y126* (p.Tyr126Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Y127C (p.Tyr127Cys), cosmic curated COSV56310
- K128=, NCI-TCGA Cosmic COSV5628, Variant assessed as somatic; low impact.
- S131F (p.Ser131Phe), NCI-TCGA TCGA novel, Ensembl rs2153929707, REVEL 0.44, CADD 27.30, Variant assessed as somatic; moderate impact.
- E133K (p.Glu133Lys), cosmic curated COSV56290, Ensembl rs2153929428
- Y134* (p.Tyr134Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Y134I (p.Tyr134Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K135E (p.Lys135Glu), cosmic curated COSV56270
- A136P (p.Ala136Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A137T (p.Ala137Thr), cosmic curated COSV56288, Ensembl rs587778592, REVEL 0.62, CADD 26.60
- K139* (p.Lys139Ter), NCI-TCGA TCGA novel, Ensembl rs2153928326, Variant assessed as somatic; high impact.
- K139N (p.Lys139Asn), cosmic curated COSV10642, Ensembl rs2153928128
- K139Q (p.Lys139Gln), cosmic curated COSV10642
- W141* (p.Trp141Ter), NCI-TCGA Cosmic COSV5626, Ensembl rs2153927782, Variant assessed as somatic; high impact.
- W141L (p.Trp141Leu), cosmic curated COSV56262, Ensembl rs2153927782
- D142G (p.Asp142Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Y144* (p.Tyr144Ter), cosmic curated COSV10963
- Y144F (p.Tyr144Phe), rs2153927262, UniProt VAR 064658, Ensembl rs2153927262, AlphaMissense 0.24, MetaLR 0.06, Benign
- L145V (p.Leu145Val), cosmic curated COSV56297, Ensembl rs2153927120
- R146* (p.Arg146Ter), cosmic curated COSV56288, Ensembl rs2153926936
- R146P (p.Arg146Pro), cosmic curated COSV56261, ExAC rs757924256, TOPMed rs757924256, gnomAD rs757924256
- T147K (p.Thr147Lys), cosmic curated COSV99046, Ensembl rs2153926747
- T147P (p.Thr147Pro), cosmic curated COSV56269, Ensembl rs2153926799
- R148* (p.Arg148Ter), cosmic curated COSV56276, Ensembl rs2153926673
- R148I (p.Arg148Ile), cosmic curated COSV56300, Ensembl rs2153926617
- N149S (p.Asn149Ser), cosmic curated COSV10963, Ensembl rs2153926554
- E150* (p.Glu150Ter), cosmic curated COSV10589, Ensembl rs2153926436
- E150Q (p.Glu150Gln), cosmic curated COSV56264, Ensembl rs2153926436
- V152F (p.Val152Phe), cosmic curated COSV99967
- Q153* (p.Gln153Ter), cosmic curated COSV56303, Ensembl rs2096738551
- G155* (p.Gly155Ter), cosmic curated COSV56294
- A157T (p.Ala157Thr), cosmic curated COSV56290, Ensembl rs2153925529, REVEL 0.02, CADD 17.80
- A157V (p.Ala157Val), cosmic curated COSV56289, Ensembl rs2153925439, REVEL 0.03, CADD 19.80
- E160* (p.Glu160Ter), NCI-TCGA Cosmic COSV5629, cosmic curated COSV56294, ExAC rs774655494, Variant assessed as somatic; high impact.
- E160A (p.Glu160Ala), UniProt VAR 064659, Uncertain significance
- E160K (p.Glu160Lys), NCI-TCGA Cosmic COSV5629, REVEL 0.09, CADD 23.10, Variant assessed as somatic; high impact.
- D161H (p.Asp161His), rs769010138, NCI-TCGA Cosmic COSV9997, cosmic curated COSV99970, ExAC rs769010138, REVEL 0.19, CADD 26.60, Variant assessed as somatic; moderate impact.
- D162N (p.Asp162Asn), NCI-TCGA TCGA novel, Ensembl rs2153924469, REVEL 0.08, CADD 23.20, Variant assessed as somatic; moderate impact.
- D163N (p.Asp163Asn), cosmic curated COSV56288, TOPMed rs2096738157
- D163V (p.Asp163Val), cosmic curated COSV56303, ExAC rs763287444, TOPMed rs763287444, gnomAD rs763287444
- E164* (p.Glu164Ter), cosmic curated COSV56302
- D165V (p.Asp165Val), cosmic curated COSV10963
- G166E (p.Gly166Glu), NCI-TCGA Cosmic COSV9996, cosmic curated COSV99969, NCI-TCGA Cosmic COSV9997, ExAC rs781444225, Variant assessed as somatic; moderate impact.
- G166R (p.Gly166Arg), cosmic curated COSV99970, ExAC rs745942186, TOPMed rs745942186, gnomAD rs745942186, REVEL 0.06, CADD 21.80
- G166V (p.Gly166Val), cosmic curated COSV99970, ExAC rs781444225, TOPMed rs781444225, gnomAD rs781444225, REVEL 0.04, CADD 21.10
- Q167* (p.Gln167Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Q170* (p.Gln170Ter), NCI-TCGA Cosmic COSV5626, cosmic curated COSV56268, Ensembl rs2153922633, Variant assessed as somatic; high impact.
- G171D (p.Gly171Asp), rs758198630, NCI-TCGA Cosmic COSV5631, ExAC rs758198630, TOPMed rs758198630, REVEL 0.08, CADD 22.60, Variant assessed as somatic; moderate impact.
- G171V (p.Gly171Val), cosmic curated COSV56311, ExAC rs758198630, TOPMed rs758198630, gnomAD rs758198630, REVEL 0.10, CADD 23.90
- T172Q (p.Thr172Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V173L (p.Val173Leu), cosmic curated COSV56313
- E175* (p.Glu175Ter), cosmic curated COSV56279
- G176A (p.Gly176Ala), cosmic curated COSV56304, ExAC rs752499912, gnomAD rs752499912, REVEL 0.03, CADD 22.30
- P179L (p.Pro179Leu), cosmic curated COSV10516, REVEL 0.07, CADD 23.10
- P179S (p.Pro179Ser), NCI-TCGA Cosmic COSV9996, cosmic curated COSV99967, Variant assessed as somatic; moderate impact.
- A180G (p.Ala180Gly), cosmic curated COSV56265
- K183* (p.Lys183Ter), cosmic curated COSV56315
- E184D (p.Glu184Asp), NCI-TCGA Cosmic COSV5626, cosmic curated COSV56264, Ensembl rs2096647650, Variant assessed as somatic; moderate impact.
- L186R (p.Leu186Arg), cosmic curated COSV56301
- E187* (p.Glu187Ter), cosmic curated COSV56287, CADD 38.00
- Q188* (p.Gln188Ter), NCI-TCGA Cosmic COSV5626, cosmic curated COSV56269, Variant assessed as somatic; high impact.
- Q188H (p.Gln188His), cosmic curated COSV10589, REVEL 0.18, CADD 24.60
- Q188R (p.Gln188Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L190P (p.Leu190Pro), cosmic curated COSV56295
- A192T (p.Ala192Thr), NCI-TCGA Cosmic COSV5630, cosmic curated COSV56307, Variant assessed as somatic; moderate impact.
- A192V (p.Ala192Val), NCI-TCGA Cosmic COSV9996, cosmic curated COSV99968, REVEL 0.17, CADD 23.10, Variant assessed as somatic; moderate impact.
- V194C (p.Val194Cys), NCI-TCGA Cosmic COSV5626, Variant assessed as somatic; high impact.
- V194G (p.Val194Gly), cosmic curated COSV99970
- T197A (p.Thr197Ala), cosmic curated COSV10516
- P199L (p.Pro199Leu), cosmic curated COSV10516
- P199S (p.Pro199Ser), cosmic curated COSV56267
- S200* (p.Ser200Ter), cosmic curated COSV56262, cosmic curated COSV56269
- R202C (p.Arg202Cys), rs765525545, NCI-TCGA Cosmic COSV5629, cosmic curated COSV56298, UniProt VAR 064660, REVEL 0.40, CADD 29.60, Benign
- I204L (p.Ile204Leu), cosmic curated COSV56292
- S205C (p.Ser205Cys), cosmic curated COSV56292
- E206K (p.Glu206Lys), rs1359676390, NCI-TCGA Cosmic COSV5626, cosmic curated COSV56269, UniProt VAR 064661, REVEL 0.22, CADD 23.90, Benign
- E206Q (p.Glu206Gln), NCI-TCGA Cosmic COSV5626, Variant assessed as somatic; moderate impact.
- Q209* (p.Gln209Ter), cosmic curated COSV56262
- Q209R (p.Gln209Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P212H (p.Pro212His), cosmic curated COSV10461, REVEL 0.54, CADD 29.40
- P212L (p.Pro212Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P212S (p.Pro212Ser), cosmic curated COSV56291, Ensembl rs2153857506, REVEL 0.45, CADD 28.50
- S213C (p.Ser213Cys), cosmic curated COSV56302
- S213P (p.Ser213Pro), cosmic curated COSV56269
- K214* (p.Lys214Ter), cosmic curated COSV56261
Public PBRM1 analysis runs
- PBRM1 analysis run — PBRM1 (1,716 variants) — completed 2026-08-18