PRKAA1 (Q13131) variants and mutations
PRKAA1 (also known as Q13131) is a human protein-coding gene encoding a 5'-AMP-activated protein kinase catalytic subunit alpha-1 protein. It provides an AMPK catalytic subunit that senses low cellular energy and shifts metabolism toward ATP production while restraining energy-consuming growth programs. Dysregulated AMPK signaling influences diabetes, cardiovascular disease, and cancer, although severe monogenic PRKAA1 disease is uncommon. This analysis covers 901 PRKAA1 variants and mutations. Of these, 64% have computational variant effect predictions. Disease context includes cardiovascular disorder, gastric carcinoma, and duodenal ulcer. Example PRKAA1 variants include M1?, R2C, and R2G.
Variant analysis overview
- Gene: PRKAA1
- Protein: Q13131
- UniProt accession: Q13131
- Organism: Homo sapiens
- Variants analyzed: 901
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 623 unspecified-consequence records; 1 stop retained variant; 127 synonymous variants; 5 stop-gained variants; 117 missense variants; 17 frameshift variants; 3 in-frame deletions; 1 in-frame insertions; 3 splice-region variants; 1 protein altering variant; 3 substitution
- Prediction scores: 579 variants have prediction scores (64% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cardiovascular disorder, gastric carcinoma, duodenal ulcer, peptic ulcer disease, gastric ulcer, alcohol drinking, neoplasm, Primary amenorrhea, cancer, hepatocellular carcinoma, breast cancer, breast carcinoma.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 binding sites; 17 post-translational modification sites.
- Structural context: 313 variants have structural context.
- PTM context: 32 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable PRKAA1 variants
Examples include M1?, R2C, R2G, R2H, R2L, R2S, R3K, R3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R2C (p.Arg2Cys), rs1033125825, NCI-TCGA Cosmic COSV5718, cosmic curated COSV57184, gnomAD rs1033125825, REVEL 0.23, CADD 25.00, Variant assessed as somatic; moderate impact.
- R2G (p.Arg2Gly), gnomAD rs1033125825, REVEL 0.13, CADD 23.90
- R2H (p.Arg2His), rs1426382824, NCI-TCGA Cosmic COSV5718, cosmic curated COSV57183, gnomAD rs1426382824, REVEL 0.10, CADD 23.80, Variant assessed as somatic; moderate impact.
- R2L (p.Arg2Leu), gnomAD rs1426382824, REVEL 0.07, CADD 23.90
- R2S (p.Arg2Ser), gnomAD rs1033125825, REVEL 0.10, CADD 23.50
- R3K (p.Arg3Lys), gnomAD rs1188565639, REVEL 0.15, CADD 17.80
- R3S (p.Arg3Ser), gnomAD rs1423481695
- L4P (p.Leu4Pro), gnomAD rs1254288802, REVEL 0.09, CADD 23.80
- S5G (p.Ser5Gly), NCI-TCGA TCGA novel, TOPMed rs1745029710, REVEL 0.08, CADD 23.00, Variant assessed as somatic; moderate impact.
- S5I (p.Ser5Ile), cosmic curated COSV10811
- S5N (p.Ser5Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S5R (p.Ser5Arg), ExAC rs773228528, gnomAD rs773228528, REVEL 0.09, CADD 23.60
- S6F (p.Ser6Phe), TOPMed rs1286001321, gnomAD rs1286001321, REVEL 0.14, CADD 21.50
- W7* (p.Trp7Ter), 1000Genomes rs551347552, ExAC rs551347552, TOPMed rs551347552, gnomAD rs551347552, CADD 37.00
- W7L (p.Trp7Leu), cosmic curated COSV99713
- W7R (p.Trp7Arg), gnomAD rs939151107, REVEL 0.08, CADD 20.70
- R8K (p.Arg8Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K9N (p.Lys9Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M10I (p.Met10Ile), Ensembl rs2112122494
- M10K (p.Met10Lys), gnomAD rs1244459595
- M10L (p.Met10Leu), rs17855679, UniProt VAR 058401, Ensembl rs17855679
- M10T (p.Met10Thr), gnomAD rs1244459595
- A11T (p.Ala11Thr), ExAC rs748031628, gnomAD rs748031628, REVEL 0.21, MetaLR 0.28
- A11V (p.Ala11Val), TOPMed rs867953599, REVEL 0.34, MetaLR 0.23
- T12I (p.Thr12Ile), TOPMed rs1382314545, gnomAD rs1382314545, REVEL 0.12, MetaLR 0.17
- T12S (p.Thr12Ser), Ensembl rs2112122438
- A13V (p.Ala13Val), Ensembl rs2112122406, REVEL 0.06, MetaLR 0.15
- E14D (p.Glu14Asp), cosmic curated COSV99713, REVEL 0.12, MetaLR 0.11
- K15M (p.Lys15Met), cosmic curated COSV57183, TOPMed rs1469720215, gnomAD rs1469720215
- K15R (p.Lys15Arg), TOPMed rs1469720215, gnomAD rs1469720215, REVEL 0.10, MetaLR 0.16
- Q16* (p.Gln16Ter), Ensembl rs2112122346
- Q16H (p.Gln16His), TOPMed rs1333113528, gnomAD rs1333113528
- Q16K (p.Gln16Lys), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99713, Variant assessed as somatic; moderate impact., in a breast cancer sample
- Q16P (p.Gln16Pro), cosmic curated COSV10461
- Q16R (p.Gln16Arg), rs928784854, cosmic curated COSV57183, UniProt VAR 035622, TOPMed rs928784854, REVEL 0.07, MetaLR 0.21, Uncertain significance, in a breast cancer sample
- K17E (p.Lys17Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H18P (p.His18Pro), rs749919427, ClinGen CA3248643, ClinVar RCV004213895, ExAC rs749919427, REVEL 0.40, MetaLR 0.28, Uncertain significance, not specified
- H18Q (p.His18Gln), ExAC rs766987004, TOPMed rs766987004, gnomAD rs766987004, REVEL 0.30, MetaLR 0.24
- H18Y (p.His18Tyr), cosmic curated COSV57184, ESP rs377040057, ExAC rs377040057, TOPMed rs377040057, REVEL 0.41, MetaLR 0.27, Uncertain significance, not specified
- D19E (p.Asp19Glu), Ensembl rs2112122271
- D19G (p.Asp19Gly), cosmic curated COSV99713
- D19V (p.Asp19Val), Ensembl rs2112122285
- G20E (p.Gly20Glu), Ensembl rs2112122242
- G20R (p.Gly20Arg), ESP rs199741192, ExAC rs199741192, TOPMed rs199741192, gnomAD rs199741192, REVEL 0.39, MetaLR 0.27
- G20W (p.Gly20Trp), ESP rs199741192, ExAC rs199741192, TOPMed rs199741192, gnomAD rs199741192
- R21L (p.Arg21Leu), NCI-TCGA Cosmic COSV5718, cosmic curated COSV57183, Variant assessed as somatic; moderate impact.
- R21W (p.Arg21Trp), Ensembl rs2112122231, REVEL 0.40, MetaLR 0.27
- V22M (p.Val22Met), cosmic curated COSV57183, ExAC rs753214385, gnomAD rs753214385, REVEL 0.31, MetaLR 0.30
- K23R (p.Lys23Arg), cosmic curated COSV10811
- I24V (p.Ile24Val), Ensembl rs2112122169, REVEL 0.18, MetaLR 0.03
- G25D (p.Gly25Asp), Ensembl rs1745024813
- G25R (p.Gly25Arg), ExAC rs759922711, TOPMed rs759922711, gnomAD rs759922711, REVEL 0.30, MetaLR 0.09
- G25S (p.Gly25Ser), ExAC rs759922711, TOPMed rs759922711, gnomAD rs759922711, REVEL 0.27, MetaLR 0.07
- H26N (p.His26Asn), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99713, Variant assessed as somatic; moderate impact.
- H26Q (p.His26Gln), ExAC rs766616413, TOPMed rs766616413, gnomAD rs766616413, REVEL 0.25, MetaLR 0.03
- Y27C (p.Tyr27Cys), rs760844250, ExAC rs760844250, gnomAD rs760844250, Variant assessed as somatic; moderate impact.
- I28F (p.Ile28Phe), cosmic curated COSV10643, gnomAD rs1209624022, REVEL 0.25, MetaLR 0.16, Uncertain significance
- I28V (p.Ile28Val), gnomAD rs1209624022, Uncertain significance, not specified
- L29R (p.Leu29Arg), TOPMed rs1745024055, gnomAD rs1745024055, REVEL 0.65, MetaLR 0.18
- L29V (p.Leu29Val), cosmic curated COSV57185
- G30S (p.Gly30Ser), TOPMed rs1745023739
- D31N (p.Asp31Asn), ExAC rs773317301, TOPMed rs773317301, gnomAD rs773317301, REVEL 0.14, MetaLR 0.07
- D31V (p.Asp31Val), gnomAD rs1429046828, REVEL 0.39, MetaLR 0.08
- D31Y (p.Asp31Tyr), ExAC rs773317301, TOPMed rs773317301, gnomAD rs773317301, REVEL 0.38, MetaLR 0.14
- T32M (p.Thr32Met), ExAC rs772007686, gnomAD rs772007686
- G34V (p.Gly34Val), Ensembl rs2112121970
- V35I (p.Val35Ile), ExAC rs774220592, gnomAD rs774220592, REVEL 0.19, MetaLR 0.17
- G36D (p.Gly36Asp), Ensembl rs2112121905
- G36R (p.Gly36Arg), gnomAD rs1331613081
- G36S (p.Gly36Ser), gnomAD rs1331613081
- T37I (p.Thr37Ile), Ensembl rs2112121887
- T37S (p.Thr37Ser), Ensembl rs2112121897
- G39C (p.Gly39Cys), cosmic curated COSV57186
- G39D (p.Gly39Asp), Ensembl rs2112121858
- G39S (p.Gly39Ser), Ensembl rs2112121866
- K42E (p.Lys42Glu), cosmic curated COSV57183
- K42N (p.Lys42Asn), cosmic curated COSV57184, Ensembl rs2112121827
- K42R (p.Lys42Arg), Ensembl rs2112121832, REVEL 0.34, MetaLR 0.04
- V43A (p.Val43Ala), TOPMed rs1205168457, gnomAD rs1205168457, REVEL 0.23, MetaLR 0.05
- V43F (p.Val43Phe), TOPMed rs1398359834, gnomAD rs1398359834, REVEL 0.21, MetaLR 0.05
- G44D (p.Gly44Asp), ESP rs377206671, ExAC rs377206671, TOPMed rs377206671, gnomAD rs377206671
- G44V (p.Gly44Val), ESP rs377206671, ExAC rs377206671, TOPMed rs377206671, gnomAD rs377206671, REVEL 0.63, MetaLR 0.12
- H46L (p.His46Leu), ESP rs374595923, ExAC rs374595923, TOPMed rs374595923, gnomAD rs374595923, REVEL 0.71, MetaLR 0.34
- E47* (p.Glu47Ter), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99713, Variant assessed as somatic; high impact.
- L48F (p.Leu48Phe), Ensembl rs755206740, REVEL 0.30, MetaLR 0.29
- L48W (p.Leu48Trp), gnomAD rs1198171523, REVEL 0.51, MetaLR 0.38
- T49S (p.Thr49Ser), ExAC rs780649839, TOPMed rs780649839, gnomAD rs780649839, REVEL 0.41, MetaLR 0.12
- G50R (p.Gly50Arg), Ensembl rs1176438429
- G50V (p.Gly50Val), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99713, Ensembl rs2112041685, Variant assessed as somatic; moderate impact.
- H51N (p.His51Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H51Y (p.His51Tyr), Ensembl rs2112041644, REVEL 0.45, MetaLR 0.30
- K52E (p.Lys52Glu), cosmic curated COSV99713
- A54D (p.Ala54Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V55L (p.Val55Leu), ExAC rs777461699, gnomAD rs777461699, REVEL 0.31, MetaLR 0.08
- L58F (p.Leu58Phe), Ensembl rs2112041582
- N59S (p.Asn59Ser), cosmic curated COSV10609, TOPMed rs930784916, REVEL 0.47, MetaLR 0.27
- R60* (p.Arg60Ter), ExAC rs754248249, gnomAD rs754248249, CADD 35.00
- R60Q (p.Arg60Gln), rs780617578, NCI-TCGA Cosmic COSV5718, cosmic curated COSV57183, ExAC rs780617578, REVEL 0.58, MetaLR 0.33, Variant assessed as somatic; moderate impact.
- R64Q (p.Arg64Gln), cosmic curated COSV57184, gnomAD rs1261017903, REVEL 0.23, MetaLR 0.25
- R64W (p.Arg64Trp), cosmic curated COSV57184, ESP rs369977975, ExAC rs369977975, TOPMed rs369977975, REVEL 0.47, MetaLR 0.49
- S65I (p.Ser65Ile), TOPMed rs1412797330, gnomAD rs1412797330
- S65N (p.Ser65Asn), rs1412797330, NCI-TCGA Cosmic COSV9971, cosmic curated COSV99713, TOPMed rs1412797330, Variant assessed as somatic; moderate impact.
- S65T (p.Ser65Thr), TOPMed rs1412797330, gnomAD rs1412797330, REVEL 0.14, MetaLR 0.26
- V68M (p.Val68Met), ExAC rs762063813, gnomAD rs762063813, REVEL 0.29, MetaLR 0.23
- G70A (p.Gly70Ala), cosmic curated COSV57185
- G70E (p.Gly70Glu), NCI-TCGA Cosmic COSV5718, cosmic curated COSV57186, Variant assessed as somatic; moderate impact.
- G70R (p.Gly70Arg), gnomAD rs1744066385, REVEL 0.40, MetaLR 0.23
- K71N (p.Lys71Asn), NCI-TCGA TCGA novel, TOPMed rs1744066197, Variant assessed as somatic; moderate impact.
- R73C (p.Arg73Cys), rs200927672, NCI-TCGA Cosmic COSV9971, cosmic curated COSV99713, 1000Genomes rs200927672, REVEL 0.52, MetaLR 0.48, Variant assessed as somatic; moderate impact.
- R73H (p.Arg73His), rs764113006, ExAC rs764113006, gnomAD rs764113006, REVEL 0.42, MetaLR 0.36, Variant assessed as somatic; moderate impact.
- R73P (p.Arg73Pro), ExAC rs764113006, gnomAD rs764113006
- I76V (p.Ile76Val), gnomAD rs1185114438, REVEL 0.24, MetaLR 0.09
- N78K (p.Asn78Lys), Ensembl rs2112041287
- L79F (p.Leu79Phe), Ensembl rs977171885
- L79P (p.Leu79Pro), TOPMed rs1290622927, gnomAD rs1290622927, REVEL 0.83, MetaLR 0.32
- K80E (p.Lys80Glu), Ensembl rs1744064699
- K80T (p.Lys80Thr), Ensembl rs2112041213
- L81V (p.Leu81Val), NCI-TCGA Cosmic COSV5718, cosmic curated COSV57184, Variant assessed as somatic; moderate impact.
- F82L (p.Phe82Leu), NCI-TCGA Cosmic COSV5718, cosmic curated COSV57182, NCI-TCGA Cosmic COSV9971, Variant assessed as somatic; moderate impact.
- R83G (p.Arg83Gly), TOPMed rs1744064171
- R83W (p.Arg83Trp), cosmic curated COSV57183
- H84Q (p.His84Gln), ESP rs377014464, TOPMed rs377014464, gnomAD rs377014464, REVEL 0.79, MetaLR 0.69
- P85S (p.Pro85Ser), cosmic curated COSV10511
- I87M (p.Ile87Met), Ensembl rs879036617
- I87V (p.Ile87Val), TOPMed rs1228019406
- K89T (p.Lys89Thr), ExAC rs769782415, gnomAD rs769782415
- Q92* (p.Gln92Ter), cosmic curated COSV57184
- V93I (p.Val93Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S95C (p.Ser95Cys), TOPMed rs201964697, gnomAD rs201964697, REVEL 0.51, MetaLR 0.25
- S95N (p.Ser95Asn), ExAC rs765077004, gnomAD rs765077004
- S95T (p.Ser95Thr), ExAC rs765077004, gnomAD rs765077004, REVEL 0.18, MetaLR 0.16
- T96I (p.Thr96Ile), Ensembl rs2112032096
- S98T (p.Ser98Thr), Ensembl rs1743958609, REVEL 0.06, MetaLR 0.03
- D99A (p.Asp99Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I100N (p.Ile100Asn), Ensembl rs945243312
- V103A (p.Val103Ala), gnomAD rs865932512, REVEL 0.37, MetaLR 0.09
- V103M (p.Val103Met), cosmic curated COSV10511
- M104L (p.Met104Leu), Ensembl rs1743957512
- E105* (p.Glu105Ter), ExAC rs759557332, gnomAD rs759557332, CADD 37.00
- E105D (p.Glu105Asp), NCI-TCGA TCGA novel, ExAC rs776543926, TOPMed rs776543926, gnomAD rs776543926, REVEL 0.41, MetaLR 0.13, Variant assessed as somatic; moderate impact.
- Y106C (p.Tyr106Cys), Ensembl rs913298651, REVEL 0.77, MetaLR 0.21
- G109A (p.Gly109Ala), Ensembl rs368064778
- G109V (p.Gly109Val), NCI-TCGA Cosmic COSV5718, cosmic curated COSV57183, Variant assessed as somatic; moderate impact.
- G110E (p.Gly110Glu), TOPMed rs1743956127
- G110R (p.Gly110Arg), Ensembl rs2112031835
- F113L (p.Phe113Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D114E (p.Asp114Glu), ExAC rs747608675, gnomAD rs747608675, REVEL 0.16, MetaLR 0.06
- Y115C (p.Tyr115Cys), rs1427249658, NCI-TCGA Cosmic COSV9971, cosmic curated COSV99713, gnomAD rs1427249658, REVEL 0.70, MetaLR 0.49, Variant assessed as somatic; moderate impact.
- I116F (p.Ile116Phe), cosmic curated COSV57183
- N119S (p.Asn119Ser), ExAC rs773952820, gnomAD rs773952820, REVEL 0.12, MetaLR 0.18
- D123G (p.Asp123Gly), TOPMed rs1195866028, gnomAD rs1195866028, REVEL 0.26, MetaLR 0.07
- D123N (p.Asp123Asn), Ensembl rs2112015576, REVEL 0.11, MetaLR 0.07
- D123Y (p.Asp123Tyr), Ensembl rs2112015576
- E124* (p.Glu124Ter), Ensembl rs2112015557
- E124G (p.Glu124Gly), TOPMed rs1743762029
- K125Q (p.Lys125Gln), TOPMed rs1743761845
- R128Q (p.Arg128Gln), rs1263050834, NCI-TCGA Cosmic COSV5718, cosmic curated COSV57186, gnomAD rs1263050834, REVEL 0.39, MetaLR 0.14, Variant assessed as somatic; moderate impact.
- R128W (p.Arg128Trp), rs865929015, NCI-TCGA Cosmic COSV5718, cosmic curated COSV57186, TOPMed rs865929015, REVEL 0.54, MetaLR 0.18, Variant assessed as somatic; moderate impact.
- R129C (p.Arg129Cys), gnomAD rs1382671155, REVEL 0.67, MetaLR 0.48
- R129G (p.Arg129Gly), gnomAD rs1382671155
- R129H (p.Arg129His), rs375372236, cosmic curated COSV57186, ESP rs375372236, ExAC rs375372236, REVEL 0.46, MetaLR 0.28, Variant assessed as somatic; moderate impact.
- R129P (p.Arg129Pro), ESP rs375372236, ExAC rs375372236, TOPMed rs375372236, gnomAD rs375372236
- L130M (p.Leu130Met), ESP rs371783627, ExAC rs371783627, TOPMed rs371783627, gnomAD rs371783627
- L130V (p.Leu130Val), ESP rs371783627, ExAC rs371783627, TOPMed rs371783627, gnomAD rs371783627, REVEL 0.30, MetaLR 0.07
- F131L (p.Phe131Leu), cosmic curated COSV57186
- Q132* (p.Gln132Ter), Ensembl rs2112015347
- Q132K (p.Gln132Lys), Ensembl rs2112015347
- Q132R (p.Gln132Arg), ExAC rs768829085, gnomAD rs768829085, REVEL 0.55, MetaLR 0.04
- Q133H (p.Gln133His), TOPMed rs1743760003, REVEL 0.61, MetaLR 0.22
- L135V (p.Leu135Val), rs975410782, ClinGen CA117211744, ClinVar RCV004515065, gnomAD rs975410782, REVEL 0.15, MetaLR 0.06, Uncertain significance, not specified
- S136C (p.Ser136Cys), NCI-TCGA Cosmic COSV5718, cosmic curated COSV57184, Variant assessed as somatic; moderate impact.
- S136F (p.Ser136Phe), cosmic curated COSV57184, Ensembl rs2112015249
- G137A (p.Gly137Ala), Ensembl rs1743759626
- G137V (p.Gly137Val), Ensembl rs1743759626
- D139G (p.Asp139Gly), TOPMed rs966217070, gnomAD rs966217070, REVEL 0.77, MetaLR 0.37
- D139H (p.Asp139His), Ensembl rs2112015210
- D139V (p.Asp139Val), TOPMed rs966217070, gnomAD rs966217070, REVEL 0.81, MetaLR 0.36
- R143G (p.Arg143Gly), Ensembl rs2112015161
- R143K (p.Arg143Lys), Ensembl rs2112015141
Public PRKAA1 analysis runs
- PRKAA1 analysis run — PRKAA1 (901 variants) — completed 2026-08-20