PRKCA (Protein kinase C alpha type) variants and mutations
PRKCA (also known as Protein kinase C alpha type) is a human protein-coding gene encoding a protein kinase C alpha type protein. Its annotated function is calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion…. It is annotated at the cytoplasm. This analysis covers 672 PRKCA variants and mutations. Of these, 68% have computational variant effect predictions. Disease context includes acute myeloid leukemia, hypertrophic cardiomyopathy, and mast cell leukemia. Example PRKCA variants include A2G, A2T, and D3D.
Variant analysis overview
- Gene: PRKCA
- Protein: Protein kinase C alpha type
- UniProt accession: P17252
- Organism: Homo sapiens
- Variants analyzed: 672
- Variant scope: all variants
- Completed: 2026-08-28
Variant and mutation evidence
- Variant composition: 556 unspecified-consequence records; 49 missense variants; 61 synonymous variants; 5 frameshift variants; 1 in-frame insertions; 1 in-frame deletions; 1 splice-region variants; 1 stop-gained variants
- Prediction scores: 460 variants have prediction scores (68% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: acute myeloid leukemia, hypertrophic cardiomyopathy, mast cell leukemia, systemic mastocytosis, mastocytosis, heart failure, neoplasm, mathematical ability, acute myeloid leukemia by FAB classification, neurodegenerative disease, cholelithiasis, dilated cardiomyopathy.
Protein structure and variant hotspots
- Protein features: 3 domains; 17 binding sites; 14 post-translational modification sites.
- Structural context: 369 variants have structural context.
- PTM context: 10 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable PRKCA variants
Examples include A2G, A2T, D3D, V4I, V4G, V4V, F5S, P6L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2G (p.Ala2Gly), TOPMed rs1169715895
- A2T (p.Ala2Thr), gnomAD 17-66302855-G-A, REVEL 0.21, CADD 25.00
- D3D (p.Asp3Asp), gnomAD 17-66302860-C-T, CADD 16.50
- V4I (p.Val4Ile), Ensembl rs571827499, REVEL 0.10, CADD 21.10
- V4G (p.Val4Gly), gnomAD 17-66302862-T-G, REVEL 0.25, CADD 22.40
- V4V (p.Val4Val), rs767049910, gnomAD 17-66302863-T-G, CADD 14.40
- F5S (p.Phe5Ser), gnomAD 17-66302861-GT-G, CADD 25.30
- P6L (p.Pro6Leu), TOPMed rs879211098, gnomAD rs879211098, REVEL 0.07, CADD 23.90
- P6R (p.Pro6Arg), TOPMed rs879211098, gnomAD rs879211098, REVEL 0.09, CADD 23.60
- P6S (p.Pro6Ser), gnomAD 17-66302867-C-T, REVEL 0.14, CADD 17.90
- P6P (p.Pro6Pro), gnomAD 17-66302869-G-T, CADD 15.60
- G7D (p.Gly7Asp), ExAC rs761243704, gnomAD rs761243704, REVEL 0.17, CADD 18.50
- G7S (p.Gly7Ser), gnomAD rs1241363040, REVEL 0.14, CADD 18.10
- G7C (p.Gly7Cys), gnomAD 17-66302870-G-T, REVEL 0.13, CADD 23.00
- N8S (p.Asn8Ser), 1000Genomes rs201024698, ExAC rs201024698, TOPMed rs201024698, gnomAD rs201024698, REVEL 0.09, CADD 18.00
- N8H (p.Asn8His), gnomAD 17-66302873-A-C, REVEL 0.07, CADD 21.90
- N8T (p.Asn8Thr), gnomAD 17-66302874-A-C, REVEL 0.08, CADD 20.90
- N8N (p.Asn8Asn), gnomAD 17-66302875-C-T, CADD 14.70
- D9H (p.Asp9His), ExAC rs754430626, TOPMed rs754430626, gnomAD rs754430626
- D9Y (p.Asp9Tyr), ExAC rs754430626, TOPMed rs754430626, gnomAD rs754430626
- S10S (p.Ser10Ser), rs1474652532, gnomAD 17-66302881-C-T, CADD 14.80
- T11P (p.Thr11Pro), gnomAD 17-66302882-A-C, REVEL 0.07, CADD 20.20
- T11K (p.Thr11Lys), gnomAD 17-66302883-C-A, REVEL 0.08, CADD 18.70
- T11M (p.Thr11Met), gnomAD 17-66302883-C-T, REVEL 0.12, CADD 21.20
- T11T (p.Thr11Thr), rs376985598, gnomAD 17-66302884-G-T, CADD 14.00
- A12G (p.Ala12Gly), gnomAD rs1567761628, REVEL 0.08, CADD 19.50
- A12T (p.Ala12Thr), NCI-TCGA TCGA novel, REVEL 0.06, CADD 15.60, Variant assessed as somatic; moderate impact.
- A12V (p.Ala12Val), gnomAD 17-66302886-C-T, REVEL 0.06, CADD 19.40
- A12A (p.Ala12Ala), rs757577723, gnomAD 17-66302887-G-A, CADD 14.80
- S13F (p.Ser13Phe), gnomAD rs1220774095, REVEL 0.05, CADD 22.40
- Q14E (p.Gln14Glu), TOPMed rs956503012, gnomAD rs956503012, REVEL 0.10, CADD 13.90
- Q14H (p.Gln14His), Ensembl rs12944151
- Q14P (p.Gln14Pro), gnomAD rs1334216181, REVEL 0.09, CADD 18.60
- D15E (p.Asp15Glu), ESP rs370194402, ExAC rs370194402, gnomAD rs370194402, REVEL 0.09, CADD 17.30
- D15D (p.Asp15Asp), gnomAD 17-66302896-C-T, CADD 14.90
- V16L (p.Val16Leu), ExAC rs758584716, gnomAD rs758584716, REVEL 0.05, CADD 22.10
- V16V (p.Val16Val), rs780083199, gnomAD 17-66302899-G-C, CADD 14.10
- A17G (p.Ala17Gly), ExAC rs747039638, TOPMed rs747039638, gnomAD rs747039638, REVEL 0.05, CADD 20.40
- A17V (p.Ala17Val), ExAC rs747039638, TOPMed rs747039638, gnomAD rs747039638, REVEL 0.06, CADD 20.20
- A17T (p.Ala17Thr), gnomAD 17-66302900-G-A, REVEL 0.07, CADD 20.90
- A17A (p.Ala17Ala), gnomAD 17-66302902-C-T, CADD 16.30
- N18H (p.Asn18His), Ensembl rs1904587640, REVEL 0.08, CADD 19.90
- N18K (p.Asn18Lys), ExAC rs542395606, gnomAD rs542395606, REVEL 0.04, CADD 18.10
- N18S (p.Asn18Ser), ExAC rs755078848, TOPMed rs755078848, gnomAD rs755078848, REVEL 0.05, CADD 20.10
- N18T (p.Asn18Thr), gnomAD 17-66302900-GC-G, CADD 24.60
- R19H (p.Arg19His), gnomAD rs1346778661, REVEL 0.21, CADD 24.70
- R19S (p.Arg19Ser), gnomAD 17-66302906-C-A, REVEL 0.12, CADD 22.30
- R19C (p.Arg19Cys), gnomAD 17-66302906-C-T, REVEL 0.41, CADD 27.40
- R19L (p.Arg19Leu), gnomAD 17-66302907-G-T, REVEL 0.15, CADD 23.10
- F20F (p.Phe20Phe), rs1432138923, gnomAD 17-66302911-C-T, CADD 16.10
- A21V (p.Ala21Val), gnomAD rs1264883870, REVEL 0.15, CADD 22.30
- A21T (p.Ala21Thr), gnomAD 17-66302912-G-A, REVEL 0.24, CADD 23.00
- A21A (p.Ala21Ala), rs1904589144, gnomAD 17-66302914-C-G, CADD 15.20
- R22H (p.Arg22His), NCI-TCGA Cosmic COSV5257, REVEL 0.80, CADD 32.00, Variant assessed as somatic; moderate impact.
- R22S (p.Arg22Ser), gnomAD 17-66302915-C-A, REVEL 0.78, CADD 28.40
- R22C (p.Arg22Cys), gnomAD 17-66302915-C-T, REVEL 0.81, CADD 32.00
- R22R (p.Arg22Arg), rs1904589351, gnomAD 17-66302917-C-G, CADD 15.60
- K23R (p.Lys23Arg), gnomAD rs1261479202, REVEL 0.20, CADD 22.10
- K23K (p.Lys23Lys), rs1904589741, gnomAD 17-66302920-A-G, CADD 15.90
- G24G (p.Gly24Gly), gnomAD 17-66302923-G-C, CADD 14.60
- A25A (p.Ala25Ala), gnomAD 17-66302926-G-T, CADD 16.00
- R27K (p.Arg27Lys), NCI-TCGA Cosmic COSV9943, Variant assessed as somatic; moderate impact.
- R27R (p.Arg27Arg), rs1267255229, gnomAD 17-66302932-G-A, CADD 13.80
- Q28R (p.Gln28Arg), Ensembl rs1904590139
- K29Q (p.Lys29Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K29K (p.Lys29Lys), gnomAD 17-66302938-G-A, CADD 15.00
- N30N (p.Asn30Asn), rs1904590338, gnomAD 17-66302941-C-T, CADD 15.10
- V31V (p.Val31Val), gnomAD 17-66302944-G-T, CADD 14.30
- H32N (p.His32Asn), Ensembl rs527574267
- H32Q (p.His32Gln), ExAC rs749195097, TOPMed rs749195097, gnomAD rs749195097, REVEL 0.50, CADD 23.60
- p.His32 Glu33insAsp, rs1460978804, gnomAD 17-66302945-C-CAC, CADD 21.60
- H32Y (p.His32Tyr), gnomAD 17-66302945-C-T, REVEL 0.29, CADD 22.60
- H32L (p.His32Leu), gnomAD 17-66302946-A-T, REVEL 0.46, CADD 22.80
- H32H (p.His32His), rs749195097, gnomAD 17-66302947-C-T, CADD 12.90
- E33K (p.Glu33Lys), NCI-TCGA Cosmic COSV5259, REVEL 0.37, CADD 23.40, Variant assessed as somatic; moderate impact.
- E33Q (p.Glu33Gln), rs987622627, NCI-TCGA Cosmic COSV5259, TOPMed rs987622627, AlphaMissense 0.22, MetaLR 0.38, Variant assessed as somatic; moderate impact.
- E33E (p.Glu33Glu), rs778640727, gnomAD 17-66302950-G-A, CADD 14.30
- V34A (p.Val34Ala), gnomAD 17-66302952-T-C, REVEL 0.45, CADD 24.70
- V34V (p.Val34Val), rs975100469, gnomAD 17-66302953-G-A, CADD 17.30
- K35R (p.Lys35Arg), gnomAD 17-66302955-A-G, REVEL 0.27, CADD 24.40
- K35K (p.Lys35Lys), rs1598576068, gnomAD 17-66302956-G-A, CADD 14.20
- D36E (p.Asp36Glu), TOPMed rs1904592218, REVEL 0.17, CADD 22.60, Uncertain significance, not specified
- D36G (p.Asp36Gly), rs2509256093, ClinGen CA400679956, ClinVar RCV004546984, Uncertain significance, not provided
- D36N (p.Asp36Asn), rs2509256085, ClinGen CA400679952, ClinVar RCV004333845, REVEL 0.21, CADD 22.80, Uncertain significance, not specified
- K38N (p.Lys38Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K38R (p.Lys38Arg), TOPMed rs1904592410, REVEL 0.23, CADD 22.90
- I40V (p.Ile40Val), gnomAD 17-66302969-A-G, REVEL 0.20, CADD 21.80
- A41S (p.Ala41Ser), gnomAD rs1193055442
- F43S (p.Phe43Ser), Ensembl rs2143079899
- F43F (p.Phe43Phe), rs745502789, gnomAD 17-66302980-C-T, CADD 17.40
- K45R (p.Lys45Arg), 1000Genomes rs200801878, ExAC rs200801878, TOPMed rs200801878, gnomAD rs200801878, REVEL 0.35, CADD 23.10, Uncertain significance, not specified
- K45K (p.Lys45Lys), rs1198438401, gnomAD 17-66302986-G-A, CADD 15.70
- Q46S (p.Gln46Ser), gnomAD 17-66302986-GC-G, CADD 27.30
- Q46Q (p.Gln46Gln), gnomAD 17-66302989-G-A, CADD 13.70
- Q46H (p.Gln46His), gnomAD 17-66302989-G-T, REVEL 0.64, CADD 26.10
- P47P (p.Pro47Pro), rs878973034, gnomAD 17-66302992-C-A, CADD 15.60
- T48I (p.Thr48Ile), Ensembl rs1567761731, REVEL 0.60, CADD 26.10
- T48N (p.Thr48Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T48P (p.Thr48Pro), gnomAD rs1321995232, REVEL 0.60, CADD 29.10
- T48T (p.Thr48Thr), rs775305804, gnomAD 17-66302995-C-G, CADD 15.10
- F49F (p.Phe49Phe), rs1381583636, gnomAD 17-66302998-C-T, CADD 17.00
- C50S (p.Cys50Ser), ExAC rs760225427, gnomAD rs760225427, REVEL 0.90, CADD 31.00
- S51R (p.Ser51Arg), gnomAD 17-66303002-A-C, REVEL 0.77, CADD 29.90
- S51S (p.Ser51Ser), gnomAD 17-66303004-C-T, CADD 15.70
- H52N (p.His52Asn), gnomAD rs1332665914, REVEL 0.74, CADD 27.40
- H52R (p.His52Arg), ExAC rs768288690, gnomAD rs768288690, REVEL 0.86, CADD 26.50
- T54T (p.Thr54Thr), rs576353595, gnomAD 17-66303013-C-T, CADD 15.80
- D55Y (p.Asp55Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F56Y (p.Phe56Tyr), gnomAD rs1229194759
- F56V (p.Phe56Val), gnomAD 17-66303017-T-G, REVEL 0.65, CADD 28.60
- F56F (p.Phe56Phe), gnomAD 17-66303019-C-T, CADD 16.70
- I57F (p.Ile57Phe), TOPMed rs1231145168, gnomAD rs1231145168
- I57M (p.Ile57Met), rs1330669334, TOPMed rs1330669334, gnomAD rs1330669334, REVEL 0.77, CADD 31.00, Variant assessed as somatic; moderate impact.
- I57V (p.Ile57Val), TOPMed rs1231145168, gnomAD rs1231145168, REVEL 0.60, CADD 26.20
- I57del (p.Ile57del), rs751044895, gnomAD 17-66303017-TTCA-, CADD 22.30
- W58C (p.Trp58Cys), NCI-TCGA Cosmic COSV9943, Variant assessed as somatic; moderate impact.
- W58R (p.Trp58Arg), gnomAD 17-66303023-T-C, REVEL 0.74, CADD 29.90
- W58L (p.Trp58Leu), gnomAD 17-66303024-G-T, REVEL 0.65, CADD 34.00
- G59R (p.Gly59Arg), gnomAD 17-66306097-G-A, REVEL 0.96, CADD 33.00
- G59G (p.Gly59Gly), rs1247973072, gnomAD 17-66306099-G-A, CADD 12.30
- F60L (p.Phe60Leu), TOPMed rs1208642777, gnomAD rs1208642777, REVEL 0.42, CADD 22.90
- G61G (p.Gly61Gly), rs773777054, gnomAD 17-66306105-G-C, CADD 11.30
- K62Q (p.Lys62Gln), gnomAD 17-66306106-A-C, REVEL 0.83, CADD 27.50
- K62R (p.Lys62Arg), gnomAD 17-66306107-A-G, REVEL 0.50, CADD 24.50
- K62K (p.Lys62Lys), gnomAD 17-66306108-A-G, CADD 13.20
- Q63Q (p.Gln63Gln), gnomAD 17-66306111-A-G, CADD 14.60
- G64S (p.Gly64Ser), Ensembl rs1904803578, REVEL 0.92, CADD 30.00
- G64A (p.Gly64Ala), gnomAD 17-66306113-G-C, REVEL 0.87, CADD 27.80
- G64G (p.Gly64Gly), rs1904803807, gnomAD 17-66306114-C-T, CADD 14.40
- F65F (p.Phe65Phe), rs763265613, gnomAD 17-66306117-C-T, CADD 15.30
- Q66H (p.Gln66His), gnomAD 17-66306120-G-C, REVEL 0.84, CADD 26.80
- Q68H (p.Gln68His), ESP rs376921936, TOPMed rs376921936, gnomAD rs376921936, REVEL 0.74, CADD 27.30, Uncertain significance, not specified
- Q68P (p.Gln68Pro), TOPMed rs1904804207, gnomAD rs1904804207, REVEL 0.91, CADD 28.40
- Q68K (p.Gln68Lys), gnomAD 17-66306122-GC-G, CADD 29.80
- Q68Q (p.Gln68Gln), gnomAD 17-66306126-A-G, CADD 22.80
- C71Y (p.Cys71Tyr), NCI-TCGA Cosmic COSV9943, Variant assessed as somatic; moderate impact.
- V74D (p.Val74Asp), Ensembl rs2144111291
- V74L (p.Val74Leu), gnomAD 17-66496215-G-C, REVEL 0.72, CADD 24.50
- K76T (p.Lys76Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R77R (p.Arg77Arg), gnomAD 17-66496224-A-C, CADD 12.80
- C78C (p.Cys78Cys), rs1390712578, gnomAD 17-66496229-C-T, CADD 12.50
- H79Y (p.His79Tyr), TOPMed rs1916468027
- H79H (p.His79His), rs759740185, gnomAD 17-66496232-T-C, CADD 11.30
- E80A (p.Glu80Ala), Ensembl rs1567858622, REVEL 0.86, CADD 25.10
- F81L (p.Phe81Leu), gnomAD rs1168036317, REVEL 0.30, CADD 16.50
- V82L (p.Val82Leu), gnomAD 17-66496239-G-C, REVEL 0.87, CADD 26.50
- V82V (p.Val82Val), rs183900316, gnomAD 17-66496241-T-A, CADD 10.70
- T83P (p.Thr83Pro), gnomAD 17-66496242-A-C, REVEL 0.66, CADD 24.10
- S85P (p.Ser85Pro), gnomAD 17-66496248-T-C, REVEL 0.53, CADD 23.10
- S85Y (p.Ser85Tyr), gnomAD 17-66496249-C-A, REVEL 0.69, CADD 23.90
- C86* (p.Cys86Ter), gnomAD rs1461673002, CADD 32.00
- C86W (p.Cys86Trp), gnomAD 17-66496253-T-G, REVEL 0.88, CADD 21.90
- P87Q (p.Pro87Gln), gnomAD 17-66496255-C-A, REVEL 0.78, CADD 29.20
- P87P (p.Pro87Pro), rs145160680, gnomAD 17-66496256-G-T, CADD 9.34
- G88V (p.Gly88Val), Ensembl rs2144111435
- A89E (p.Ala89Glu), TOPMed rs915754719, REVEL 0.41, CADD 22.90
- A89V (p.Ala89Val), TOPMed rs915754719, REVEL 0.24, CADD 22.60
- A89A (p.Ala89Ala), rs775784706, gnomAD 17-66496262-G-A, CADD 7.03
- D90G (p.Asp90Gly), gnomAD rs1450533796, REVEL 0.41, CADD 24.70
- D90V (p.Asp90Val), gnomAD 17-66496264-A-T, REVEL 0.50, CADD 23.70
- D90E (p.Asp90Glu), gnomAD 17-66496265-T-G, REVEL 0.25, CADD 16.90
- K91K (p.Lys91Lys), rs760628881, gnomAD 17-66496268-G-A, CADD 7.29
- G92E (p.Gly92Glu), NCI-TCGA TCGA novel, gnomAD rs1916469606, Variant assessed as somatic; moderate impact.
- G92G (p.Gly92Gly), rs764254597, gnomAD 17-66496271-A-C, CADD 7.51
- P93P (p.Pro93Pro), rs750302415, gnomAD 17-66496274-C-T, CADD 0.35
- D94N (p.Asp94Asn), rs758445868, NCI-TCGA Cosmic COSV5258, ExAC rs758445868, TOPMed rs758445868, REVEL 0.19, CADD 23.40, Variant assessed as somatic; moderate impact.
- D94Y (p.Asp94Tyr), gnomAD 17-66496275-G-T, REVEL 0.56, CADD 25.40
- T95S (p.Thr95Ser), ExAC rs766268531, gnomAD rs766268531, REVEL 0.10, CADD 16.40
- D96E (p.Asp96Glu), ESP rs375714097, ExAC rs375714097, TOPMed rs375714097, gnomAD rs375714097, REVEL 0.32, CADD 15.40, Uncertain significance, PRKCA-related disorder
- D96N (p.Asp96Asn), NCI-TCGA Cosmic COSV9943, Variant assessed as somatic; moderate impact.
- D97N (p.Asp97Asn), Ensembl rs1971292851
- D97E (p.Asp97Glu), rs780188872, gnomAD 17-66641356-A-AGA, CADD 32.00
- P98S (p.Pro98Ser), UniProt VAR 042301, Uncertain significance, in a colorectal adenocarcinoma sample
- P98L (p.Pro98Leu), gnomAD 17-66641359-C-T, REVEL 0.31, CADD 22.60
- P98P (p.Pro98Pro), rs868655294, gnomAD 17-66641360-C-T, CADD 9.38
- R99R (p.Arg99Arg), rs758786156, gnomAD 17-66641363-G-A, CADD 9.42
- S100N (p.Ser100Asn), ExAC rs762002113, gnomAD rs762002113, REVEL 0.39, CADD 22.00
- S100S (p.Ser100Ser), gnomAD 17-66641366-C-T, CADD 12.50
- K101R (p.Lys101Arg), ExAC rs766356302, TOPMed rs766356302, gnomAD rs766356302, REVEL 0.24, CADD 22.90
- K101K (p.Lys101Lys), gnomAD 17-66641369-G-A, CADD 10.10
Public PRKCA analysis runs
- PRKCA analysis run — PRKCA (672 variants) — completed 2026-08-28