PIK3CB (P42338) variants and mutations
PIK3CB (also known as P42338) is a human protein-coding gene encoding a phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform protein. It generates PIP3 downstream of growth-factor and G-protein-coupled receptors, activating AKT and other signaling pathways that regulate survival and metabolism. Some PTEN-deficient tumors become particularly dependent on p110beta activity, making it a therapeutic target. This analysis covers 1,885 PIK3CB variants and mutations. Of these, 47% have computational variant effect predictions. Disease context includes cancer, neurodegenerative disease, and Alzheimer disease. Example PIK3CB variants include C2F, C2G, and C2S.
Variant analysis overview
- Gene: PIK3CB
- Protein: P42338
- UniProt accession: P42338
- Organism: Homo sapiens
- Variants analyzed: 1885
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 1,706 unspecified-consequence records; 91 synonymous variants; 70 missense variants; 3 in-frame deletions; 8 frameshift variants; 6 splice-region variants; 1 stop-gained variants; 5 substitution
- Prediction scores: 888 variants have prediction scores (47% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cancer, neurodegenerative disease, Alzheimer disease, Parkinson disease, lysosomal storage disease, multiple sclerosis, non-small cell lung carcinoma, breast cancer, prostate adenocarcinoma, head and neck squamous cell carcinoma, esophageal adenocarcinoma, kidney neoplasm.
Protein structure and variant hotspots
- Protein features: 5 domains; 2 post-translational modification sites.
- Structural context: 1,415 variants have structural context.
- PTM context: 5 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable PIK3CB variants
Examples include C2F, C2G, C2S, S4C, S4G, S4R, S4T, F5L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- C2F (p.Cys2Phe), Ensembl rs2045629362, CADD 22.50, PolyPhen-2 0.00
- C2G (p.Cys2Gly), cosmic curated COSV56687
- C2S (p.Cys2Ser), Ensembl rs2045629362
- S4C (p.Ser4Cys), cosmic curated COSV56683
- S4G (p.Ser4Gly), cosmic curated COSV10000, CADD 5.90, PolyPhen-2 0.01
- S4R (p.Ser4Arg), cosmic curated COSV10000, TOPMed rs2045629272
- S4T (p.Ser4Thr), Ensembl rs2045629232
- F5L (p.Phe5Leu), TOPMed rs1163476279, gnomAD rs1163476279, CADD 18.70, PolyPhen-2 0.00
- F5S (p.Phe5Ser), cosmic curated COSV10438
- I6V (p.Ile6Val), ExAC rs781669505, gnomAD rs781669505, CADD 17.50, PolyPhen-2 0.00
- M7V (p.Met7Val), Ensembl rs2108734368, CADD 25.10, PolyPhen-2 0.99
- P9S (p.Pro9Ser), cosmic curated COSV56685, CADD 26.20, PolyPhen-2 0.98
- A10T (p.Ala10Thr), cosmic curated COSV10000, Ensembl rs2108734345, CADD 23.40, PolyPhen-2 0.33
- A10V (p.Ala10Val), Ensembl rs2108734337, CADD 22.80, PolyPhen-2 0.02
- M11V (p.Met11Val), TOPMed rs2045629062, CADD 15.70, PolyPhen-2 0.00
- A12S (p.Ala12Ser), Ensembl rs2108734303
- A12T (p.Ala12Thr), Ensembl rs2108734303
- D13G (p.Asp13Gly), rs752021744, ClinGen CA2639656, ClinVar RCV004168718, ExAC rs752021744, CADD 22.40, PolyPhen-2 0.01, Uncertain significance, not specified
- D13V (p.Asp13Val), ExAC rs752021744, gnomAD rs752021744, Uncertain significance
- I14L (p.Ile14Leu), cosmic curated COSV56691
- L15I (p.Leu15Ile), cosmic curated COSV56686
- D16V (p.Asp16Val), ExAC rs766489153, TOPMed rs766489153, gnomAD rs766489153, CADD 26.30, PolyPhen-2 0.49
- I17F (p.Ile17Phe), cosmic curated COSV56691
- I17M (p.Ile17Met), TOPMed rs2045628748
- I17N (p.Ile17Asn), ExAC rs763276798, gnomAD rs763276798, CADD 24.00, PolyPhen-2 0.01
- I17V (p.Ile17Val), TOPMed rs1172688851, CADD 18.20, PolyPhen-2 0.01
- W18* (p.Trp18Ter), cosmic curated COSV10000
- A19S (p.Ala19Ser), Ensembl rs2108734204
- A19V (p.Ala19Val), cosmic curated COSV10000, 1000Genomes rs148660928, ExAC rs148660928, TOPMed rs148660928, CADD 22.60, PolyPhen-2 0.22, Uncertain significance, not specified
- V20L (p.Val20Leu), Ensembl rs2108734158
- V20M (p.Val20Met), Ensembl rs2108734158
- D21H (p.Asp21His), cosmic curated COSV56689
- D21Y (p.Asp21Tyr), TOPMed rs576986268, CADD 23.50, PolyPhen-2 0.01
- S22L (p.Ser22Leu), TOPMed rs1195526427, gnomAD rs1195526427, CADD 23.10
- Q23H (p.Gln23His), gnomAD rs1443328803, CADD 18.00, PolyPhen-2 0.01
- I24M (p.Ile24Met), TOPMed rs1304985158
- A25S (p.Ala25Ser), ESP rs374448453, ExAC rs374448453, TOPMed rs374448453, gnomAD rs374448453, CADD 14.80, PolyPhen-2 0.03
- A25T (p.Ala25Thr), ESP rs374448453, ExAC rs374448453, TOPMed rs374448453, gnomAD rs374448453, CADD 18.10, PolyPhen-2 0.07
- S26C (p.Ser26Cys), ExAC rs760521881, TOPMed rs760521881, gnomAD rs760521881, Uncertain significance
- S26Y (p.Ser26Tyr), rs760521881, ClinGen CA2639649, cosmic curated COSV10517, ClinVar RCV004209152, CADD 23.00, PolyPhen-2 0.01, Uncertain significance, not specified
- G28D (p.Gly28Asp), Ensembl rs2045627968
- G28S (p.Gly28Ser), cosmic curated COSV10000, gnomAD rs1347448883, CADD 19.90, PolyPhen-2 0.00
- G28R (p.Gly28Arg), rs958541551, []
- S29C (p.Ser29Cys), cosmic curated COSV10878, TOPMed rs1328338753
- S29F (p.Ser29Phe), TOPMed rs1328338753, CADD 23.60, PolyPhen-2 0.09
- S29P (p.Ser29Pro), TOPMed rs1293454308, CADD 17.60, PolyPhen-2 0.00
- I30T (p.Ile30Thr), Ensembl rs2045627824
- P31S (p.Pro31Ser), gnomAD rs1298339692, CADD 15.20, PolyPhen-2 0.00
- V32L (p.Val32Leu), ExAC rs775392228, gnomAD rs775392228, CADD 19.60, PolyPhen-2 0.03
- V32M (p.Val32Met), ExAC rs775392228, gnomAD rs775392228, CADD 21.60, PolyPhen-2 0.21
- F34L (p.Phe34Leu), ESP rs145008785, gnomAD rs145008785
- L35P (p.Leu35Pro), Ensembl rs2108733950, CADD 27.90, PolyPhen-2 1.00
- L35V (p.Leu35Val), cosmic curated COSV10000
- L36F (p.Leu36Phe), cosmic curated COSV10000, gnomAD rs1295285143, CADD 23.10, PolyPhen-2 0.98
- P37L (p.Pro37Leu), cosmic curated COSV10878
- P37S (p.Pro37Ser), Ensembl rs2108733904, CADD 25.50, PolyPhen-2 1.00
- T38N (p.Thr38Asn), cosmic curated COSV10000
- T38S (p.Thr38Ser), Ensembl rs2108733901
- G39E (p.Gly39Glu), cosmic curated COSV56689
- G39R (p.Gly39Arg), ESP rs370148572, ExAC rs370148572, TOPMed rs370148572, gnomAD rs370148572, CADD 26.60, PolyPhen-2 1.00
- I42M (p.Ile42Met), TOPMed rs751891962, gnomAD rs751891962
- L44M (p.Leu44Met), ExAC rs778448578, TOPMed rs778448578, gnomAD rs778448578, CADD 14.40, PolyPhen-2 0.34
- E45G (p.Glu45Gly), gnomAD rs2045627224, CADD 23.60, PolyPhen-2 0.10
- V46E (p.Val46Glu), cosmic curated COSV56687
- V46I (p.Val46Ile), Ensembl rs2108733827
- P47A (p.Pro47Ala), ExAC rs770363808, TOPMed rs770363808, gnomAD rs770363808, CADD 21.90, PolyPhen-2 0.23, Uncertain significance, not specified
- P47L (p.Pro47Leu), cosmic curated COSV56688, CADD 24.00, PolyPhen-2 0.77
- P47S (p.Pro47Ser), ExAC rs770363808, TOPMed rs770363808, gnomAD rs770363808, CADD 18.90, PolyPhen-2 0.12
- R48L (p.Arg48Leu), cosmic curated COSV10000
- R48Q (p.Arg48Gln), cosmic curated COSV56685, gnomAD rs1374478281, CADD 24.20, PolyPhen-2 0.96
- R48W (p.Arg48Trp), cosmic curated COSV56689, 1000Genomes rs545189148, ExAC rs545189148, gnomAD rs545189148, CADD 26.00, PolyPhen-2 0.97
- E49G (p.Glu49Gly), gnomAD rs2045627011, CADD 24.10, PolyPhen-2 0.10
- A50G (p.Ala50Gly), gnomAD rs1168911534, CADD 27.60, PolyPhen-2 0.75
- A50P (p.Ala50Pro), cosmic curated COSV56688, ESP rs375632149, TOPMed rs375632149, gnomAD rs375632149
- A50S (p.Ala50Ser), ESP rs375632149, TOPMed rs375632149, gnomAD rs375632149
- A50T (p.Ala50Thr), ESP rs375632149, TOPMed rs375632149, gnomAD rs375632149, CADD 21.10, PolyPhen-2 0.17
- S53F (p.Ser53Phe), TOPMed rs1184724506, gnomAD rs1184724506, CADD 24.40, PolyPhen-2 0.76
- S53Y (p.Ser53Tyr), TOPMed rs1184724506, gnomAD rs1184724506, CADD 25.50, PolyPhen-2 0.76
- Y54N (p.Tyr54Asn), cosmic curated COSV56689
- I55F (p.Ile55Phe), cosmic curated COSV56683
- I55S (p.Ile55Ser), gnomAD rs1387834373, CADD 29.50, PolyPhen-2 0.97
- I55V (p.Ile55Val), TOPMed rs2045626749, gnomAD rs2045626749, CADD 23.20, PolyPhen-2 0.28
- Q57E (p.Gln57Glu), ExAC rs764363710, gnomAD rs764363710, CADD 19.70, PolyPhen-2 0.01
- Q57H (p.Gln57His), ExAC rs780416905, TOPMed rs780416905, gnomAD rs780416905
- Q57R (p.Gln57Arg), ExAC rs751840740, TOPMed rs751840740, gnomAD rs751840740, CADD 24.20, PolyPhen-2 0.02
- M58I (p.Met58Ile), gnomAD rs1250772038, CADD 16.30, PolyPhen-2 0.00
- M58L (p.Met58Leu), ExAC rs748775308, TOPMed rs748775308, gnomAD rs748775308, CADD 18.60, PolyPhen-2 0.00
- M58V (p.Met58Val), ExAC rs748775308, TOPMed rs748775308, gnomAD rs748775308, CADD 12.80, PolyPhen-2 0.00
- W60R (p.Trp60Arg), cosmic curated COSV10608
- K61N (p.Lys61Asn), TOPMed rs2045558802
- K61T (p.Lys61Thr), cosmic curated COSV56689
- H64P (p.His64Pro), TOPMed rs2045558545
- H64Y (p.His64Tyr), Ensembl rs934538393, CADD 23.10, PolyPhen-2 0.15
- N65S (p.Asn65Ser), ExAC rs747491179, TOPMed rs747491179, gnomAD rs747491179, CADD 13.90, PolyPhen-2 0.00
- P67S (p.Pro67Ser), ExAC rs780428632, gnomAD rs780428632, CADD 26.00, PolyPhen-2 0.99
- M68I (p.Met68Ile), cosmic curated COSV56687, Ensembl rs902540248, CADD 22.80, PolyPhen-2 0.03
- M68L (p.Met68Leu), TOPMed rs1333841554, gnomAD rs1333841554, CADD 15.00
- M68V (p.Met68Val), cosmic curated COSV56687, TOPMed rs1333841554, gnomAD rs1333841554, CADD 21.50, PolyPhen-2 0.04
- F69Y (p.Phe69Tyr), ExAC rs758784705, gnomAD rs758784705, CADD 22.30, PolyPhen-2 0.12
- N70D (p.Asn70Asp), TOPMed rs1030113277, CADD 19.60, PolyPhen-2 0.10
- N70H (p.Asn70His), cosmic curated COSV10586, TOPMed rs1030113277, CADD 16.60, PolyPhen-2 0.00
- N70S (p.Asn70Ser), ESP rs370600009, TOPMed rs370600009, CADD 18.70, PolyPhen-2 0.00, Uncertain significance, not specified
- N70T (p.Asn70Thr), ESP rs370600009, TOPMed rs370600009
- L71F (p.Leu71Phe), ExAC rs746275978, gnomAD rs746275978, CADD 23.40, PolyPhen-2 0.82
- L71P (p.Leu71Pro), gnomAD rs1370733608, CADD 24.90, PolyPhen-2 0.86
- L72F (p.Leu72Phe), cosmic curated COSV10517, Ensembl rs2108722089
- M73V (p.Met73Val), ExAC rs779251088, TOPMed rs779251088, gnomAD rs779251088, CADD 15.20, PolyPhen-2 0.00, Uncertain significance, not specified
- D74A (p.Asp74Ala), ExAC rs757588885, TOPMed rs757588885, gnomAD rs757588885
- D74G (p.Asp74Gly), ExAC rs757588885, TOPMed rs757588885, gnomAD rs757588885, CADD 23.70, PolyPhen-2 0.11
- D74N (p.Asp74Asn), cosmic curated COSV56684
- I75T (p.Ile75Thr), TOPMed rs1187901141, CADD 22.50, PolyPhen-2 0.19
- S77F (p.Ser77Phe), Ensembl rs1576392688
- Y78C (p.Tyr78Cys), cosmic curated COSV56687, TOPMed rs1351165932, gnomAD rs1351165932, CADD 28.80, PolyPhen-2 1.00, Uncertain significance, not specified
- Y78H (p.Tyr78His), cosmic curated COSV56688
- M79L (p.Met79Leu), 1000Genomes rs2108722003, CADD 22.60
- M79T (p.Met79Thr), Ensembl rs2045557581
- A81G (p.Ala81Gly), cosmic curated COSV56687
- A81S (p.Ala81Ser), Ensembl rs772351098, CADD 20.40, PolyPhen-2 0.00
- C82S (p.Cys82Ser), cosmic curated COSV10806
- C82Y (p.Cys82Tyr), Ensembl rs2045557446
- T86N (p.Thr86Asn), gnomAD rs1461410687, CADD 21.20, PolyPhen-2 0.02
- A87T (p.Ala87Thr), Ensembl rs2108721912
- A87V (p.Ala87Val), Ensembl rs2108721902
- V88L (p.Val88Leu), Ensembl rs1576392661, CADD 23.10
- Y89F (p.Tyr89Phe), ExAC rs764217455, TOPMed rs764217455, gnomAD rs764217455, CADD 22.10, PolyPhen-2 0.03
- Y89H (p.Tyr89His), gnomAD rs1161845385, CADD 22.40, PolyPhen-2 0.00
- Y89C (p.Tyr89Cys), rs993589147, []
- E90* (p.Glu90Ter), Ensembl rs2108721838
- L92F (p.Leu92Phe), gnomAD rs1192049247, CADD 26.30, PolyPhen-2 0.89
- L92P (p.Leu92Pro), TOPMed rs1489490754, gnomAD rs1489490754, CADD 27.80, PolyPhen-2 1.00
- E93K (p.Glu93Lys), Ensembl rs2108721779
- E93Q (p.Glu93Gln), cosmic curated COSV56691
- D94A (p.Asp94Ala), Ensembl rs3729696
- D94H (p.Asp94His), cosmic curated COSV10000
- E95K (p.Glu95Lys), Ensembl rs2108721741
- T96A (p.Thr96Ala), cosmic curated COSV56683, ExAC rs752616498, TOPMed rs752616498, gnomAD rs752616498, CADD 22.50, PolyPhen-2 0.40
- T96K (p.Thr96Lys), cosmic curated COSV10608
- T96R (p.Thr96Arg), Ensembl rs2108721708
- R97* (p.Arg97Ter), Ensembl rs2108721690
- R97G (p.Arg97Gly), cosmic curated COSV10000
- R97P (p.Arg97Pro), gnomAD rs1467994756
- R97Q (p.Arg97Gln), cosmic curated COSV56688, gnomAD rs1467994756, CADD 24.50, PolyPhen-2 0.48
- R98T (p.Arg98Thr), Ensembl rs2108721657, CADD 26.30, PolyPhen-2 0.99
- C100Y (p.Cys100Tyr), ExAC rs767424578, CADD 25.60, PolyPhen-2 0.96
- D101V (p.Asp101Val), Ensembl rs2108721603, CADD 28.20, PolyPhen-2 1.00
- D101Y (p.Asp101Tyr), cosmic curated COSV10000
- R103K (p.Arg103Lys), cosmic curated COSV56684, ExAC rs774181749, gnomAD rs774181749, CADD 21.10, PolyPhen-2 0.21
- R103T (p.Arg103Thr), cosmic curated COSV56687
- P104F (p.Pro104Phe), cosmic curated COSV10461
- P104H (p.Pro104His), cosmic curated COSV56685
- P104S (p.Pro104Ser), cosmic curated COSV10000
- L106F (p.Leu106Phe), cosmic curated COSV10731
- P107R (p.Pro107Arg), gnomAD rs1219491121, CADD 27.00, PolyPhen-2 0.97
- V112L (p.Val112Leu), cosmic curated COSV56689
- V112M (p.Val112Met), cosmic curated COSV10586, CADD 24.70, PolyPhen-2 0.73
- T113I (p.Thr113Ile), TOPMed rs2045556291, gnomAD rs2045556291, CADD 23.80
- R114T (p.Arg114Thr), cosmic curated COSV56682
- S115R (p.Ser115Arg), Ensembl rs2045556195
- C116F (p.Cys116Phe), gnomAD rs1323338734, CADD 25.60, PolyPhen-2 0.74
- D117E (p.Asp117Glu), TOPMed rs2045556094, gnomAD rs2045556094, CADD 17.40, PolyPhen-2 0.51
- P118S (p.Pro118Ser), 1000Genomes rs201174029, ExAC rs201174029, CADD 22.50, PolyPhen-2 0.03
- G119A (p.Gly119Ala), Ensembl rs1483689001
- E120Q (p.Glu120Gln), Ensembl rs2108721381
- K121E (p.Lys121Glu), Ensembl rs2108721363
- D123N (p.Asp123Asn), cosmic curated COSV10731, CADD 19.40, PolyPhen-2 0.00
- S124* (p.Ser124Ter), cosmic curated COSV10461, cosmic curated COSV56682, CADD 37.00
- S124P (p.Ser124Pro), TOPMed rs900228786, CADD 27.70, PolyPhen-2 0.89
- S124T (p.Ser124Thr), TOPMed rs900228786, CADD 22.40, PolyPhen-2 0.12
- V128D (p.Val128Asp), Ensembl rs2108721266
- V128I (p.Val128Ile), cosmic curated COSV10000, Ensembl rs2108721276
- L129F (p.Leu129Phe), cosmic curated COSV56687
- I130M (p.Ile130Met), TOPMed rs1038798850, CADD 25.30, PolyPhen-2 0.98
- I130T (p.Ile130Thr), TOPMed rs1406759016
- K132T (p.Lys132Thr), cosmic curated COSV56691
- G133S (p.Gly133Ser), gnomAD rs1323215077, CADD 35.00, PolyPhen-2 0.47
- L134Q (p.Leu134Gln), TOPMed rs2045271011
- L134V (p.Leu134Val), gnomAD rs1450143044, CADD 22.40, PolyPhen-2 0.74
- H135N (p.His135Asn), cosmic curated COSV10000, CADD 23.10, PolyPhen-2 0.13
- D138H (p.Asp138His), rs373262346, ClinGen CA2639582, cosmic curated COSV56687, ClinVar RCV004178178, CADD 25.40, PolyPhen-2 0.91, Uncertain significance, not specified
- D138N (p.Asp138Asn), cosmic curated COSV10731
Public PIK3CB analysis runs
- PIK3CB analysis run — PIK3CB (1,885 variants) — completed 2026-08-21