KCNJ3 (P48549) variants and mutations
KCNJ3 (also known as P48549) is a human protein-coding gene encoding a g protein-activated inward rectifier potassium channel 1 protein. Together with GIRK-family partners, it carries inhibitory potassium current downstream of G-protein-coupled receptors and helps slow pacemaker activity and dampen neuronal excitability. Altered signaling can affect cardiac rhythm and neural circuits, although definitive monogenic disease associations are limited. This analysis covers 890 KCNJ3 variants and mutations. Of these, 64% have computational variant effect predictions. Disease context includes atrial fibrillation, intelligence, and smoking initiation. Example KCNJ3 variants include S2F, S2P, and S2S.
Variant analysis overview
- Gene: KCNJ3
- Protein: P48549
- UniProt accession: P48549
- Organism: Homo sapiens
- Variants analyzed: 890
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 525 unspecified-consequence records; 150 missense variants; 202 synonymous variants; 4 stop-gained variants; 6 frameshift variants; 1 in-frame insertions; 1 splice-region variants; 1 stop lost; 1 in-frame deletions
- Prediction scores: 566 variants have prediction scores (64% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: atrial fibrillation, intelligence, smoking initiation, mathematical ability, dentures, familial atrial fibrillation, cardiac arrhythmia, atrial flutter, risk-taking behaviour, response to xenobiotic stimulus, sialolithiasis, alcohol drinking.
Protein structure and variant hotspots
- Protein features: 2 transmembrane segments; 3 post-translational modification sites.
- Structural context: 66 variants have structural context.
- PTM context: 4 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, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable KCNJ3 variants
Examples include S2F, S2P, S2S, A3G, A3S, A3V, A3A, L4F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2F (p.Ser2Phe), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54536, REVEL 0.66, CADD 26.20, Variant assessed as somatic; moderate impact.
- S2P (p.Ser2Pro), gnomAD 2-154698779-T-C, REVEL 0.55, CADD 27.20
- S2S (p.Ser2Ser), gnomAD 2-154698781-T-C, CADD 15.30
- A3G (p.Ala3Gly), cosmic curated COSV54540, gnomAD rs1354793156
- A3S (p.Ala3Ser), Ensembl rs772946604
- A3V (p.Ala3Val), gnomAD rs1354793156, REVEL 0.29, CADD 23.40
- A3A (p.Ala3Ala), rs1436354741, gnomAD 2-154698784-A-T, CADD 15.40
- L4F (p.Leu4Phe), Ensembl rs1684833718
- L4L (p.Leu4Leu), gnomAD 2-154698787-C-A, CADD 12.50
- R5Q (p.Arg5Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R5L (p.Arg5Leu), gnomAD 2-154698789-G-T, REVEL 0.61, CADD 29.50
- R6W (p.Arg6Trp), Ensembl rs2105142390
- K7E (p.Lys7Glu), Ensembl rs1574424513
- F8L (p.Phe8Leu), ExAC rs765048252, TOPMed rs765048252, gnomAD rs765048252, REVEL 0.32, CADD 23.00
- F8S (p.Phe8Ser), ESP rs376120670, ExAC rs376120670, TOPMed rs376120670, gnomAD rs376120670, REVEL 0.46, CADD 24.00
- G9V (p.Gly9Val), gnomAD 2-154698801-G-T, REVEL 0.46, CADD 27.10
- D10E (p.Asp10Glu), Ensembl rs866557536, NCI-TCGA Cosmic COSV5453, NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, REVEL 0.29, CADD 17.40, Variant assessed as somatic; moderate impact.
- D11N (p.Asp11Asn), rs750258804, NCI-TCGA Cosmic COSV5454, cosmic curated COSV54546, ExAC rs750258804, Variant assessed as somatic; moderate impact.
- D11Y (p.Asp11Tyr), ExAC rs750258804, TOPMed rs750258804, gnomAD rs750258804, REVEL 0.61, CADD 29.90
- D11D (p.Asp11Asp), rs1389336037, gnomAD 2-154698808-T-C, CADD 13.40
- Y12C (p.Tyr12Cys), TOPMed rs1271832848, REVEL 0.74, CADD 28.70
- Y12H (p.Tyr12His), gnomAD 2-154698809-T-C, REVEL 0.52, CADD 23.80
- Q13* (p.Gln13Ter), cosmic curated COSV10732, Ensembl rs866656724
- Q13H (p.Gln13His), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, REVEL 0.51, CADD 25.60, Variant assessed as somatic; moderate impact.
- Q13Q (p.Gln13Gln), gnomAD 2-154698814-G-A, CADD 12.00
- V14I (p.Val14Ile), ESP rs370581540, ExAC rs370581540, TOPMed rs370581540, gnomAD rs370581540, REVEL 0.42, CADD 21.10
- V14L (p.Val14Leu), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, Variant assessed as somatic; moderate impact.
- V15M (p.Val15Met), gnomAD 2-154698818-G-A, REVEL 0.61, CADD 28.60
- V15V (p.Val15Val), gnomAD 2-154698820-G-A, CADD 13.00
- T16N (p.Thr16Asn), Ensembl rs1574424545
- T17I (p.Thr17Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S18* (p.Ser18Ter), NCI-TCGA Cosmic COSV5453, Variant assessed as somatic; high impact.
- S18A (p.Ser18Ala), ExAC rs779681417, TOPMed rs779681417, gnomAD rs779681417, REVEL 0.20, CADD 22.30
- S18S (p.Ser18Ser), rs1351839298, gnomAD 2-154698829-G-T, CADD 10.20
- G21A (p.Gly21Ala), TOPMed rs1684834772
- G21C (p.Gly21Cys), Ensembl rs1684834703
- G21V (p.Gly21Val), NCI-TCGA Cosmic COSV5454, cosmic curated COSV54547, Variant assessed as somatic; moderate impact.
- G21D (p.Gly21Asp), gnomAD 2-154698837-G-A, REVEL 0.30, CADD 23.20
- G21G (p.Gly21Gly), gnomAD 2-154698838-C-T, CADD 12.20
- S22L (p.Ser22Leu), cosmic curated COSV54537, Ensembl rs1684834828
- S22S (p.Ser22Ser), gnomAD 2-154698841-G-A, CADD 13.40
- G23C (p.Gly23Cys), TOPMed rs1684835002
- G23G (p.Gly23Gly), rs754609395, gnomAD 2-154698844-C-T, CADD 13.50
- L24L (p.Leu24Leu), gnomAD 2-154698847-G-A, CADD 12.10
- P26S (p.Pro26Ser), gnomAD 2-154698851-C-T, REVEL 0.33, CADD 21.10
- P26H (p.Pro26His), gnomAD 2-154698852-C-A, REVEL 0.35, CADD 22.40
- P26P (p.Pro26Pro), rs1275532181, gnomAD 2-154698853-C-G, CADD 13.40
- Q27Q (p.Gln27Gln), gnomAD 2-154698856-G-A, CADD 11.70
- G28E (p.Gly28Glu), ExAC rs780801298, gnomAD rs780801298
- G28R (p.Gly28Arg), cosmic curated COSV10459, gnomAD rs1308324324, REVEL 0.37, CADD 23.20
- G28V (p.Gly28Val), cosmic curated COSV10732, ExAC rs780801298, gnomAD rs780801298, REVEL 0.32, CADD 22.30
- G28W (p.Gly28Trp), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, Variant assessed as somatic; moderate impact.
- P29P (p.Pro29Pro), rs1204045967, gnomAD 2-154698862-A-G, CADD 8.10
- G30S (p.Gly30Ser), gnomAD 2-154698863-G-A, REVEL 0.19, CADD 20.90
- Q31L (p.Gln31Leu), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54539, Variant assessed as somatic; moderate impact.
- D32A (p.Asp32Ala), Ensembl rs1574424576
- D32E (p.Asp32Glu), NCI-TCGA Cosmic COSV5454, cosmic curated COSV54545, Variant assessed as somatic; moderate impact.
- D32N (p.Asp32Asn), cosmic curated COSV54535, Ensembl rs1684835657
- D32Y (p.Asp32Tyr), Ensembl rs1684835657
- P33A (p.Pro33Ala), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99716, Variant assessed as somatic; moderate impact.
- P33P (p.Pro33Pro), rs747578225, gnomAD 2-154698874-T-C, CADD 12.90
- Q34* (p.Gln34Ter), NCI-TCGA Cosmic COSV5453, NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, Variant assessed as somatic; high impact.
- Q34E (p.Gln34Glu), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54535, NCI-TCGA Cosmic COSV9971, Variant assessed as somatic; moderate impact.
- Q35H (p.Gln35His), TOPMed rs1170408270, gnomAD rs1170408270, REVEL 0.19, CADD 21.50, Uncertain significance, not specified
- Q35L (p.Gln35Leu), gnomAD rs1469836479, REVEL 0.20, CADD 22.60
- Q36R (p.Gln36Arg), Ensembl rs961260243
- Q36E (p.Gln36Glu), gnomAD 2-154698881-C-G, REVEL 0.27, CADD 16.40
- Q36H (p.Gln36His), gnomAD 2-154698883-G-T, REVEL 0.30, CADD 20.50
- L37F (p.Leu37Phe), ExAC rs770362925, TOPMed rs770362925, gnomAD rs770362925
- L37V (p.Leu37Val), ExAC rs770362925, TOPMed rs770362925, gnomAD rs770362925, REVEL 0.18, CADD 16.70
- L37L (p.Leu37Leu), rs1252369531, gnomAD 2-154698886-T-A, CADD 6.40
- V38A (p.Val38Ala), NCI-TCGA Cosmic COSV5454, cosmic curated COSV54540, Variant assessed as somatic; moderate impact.
- V38L (p.Val38Leu), TOPMed rs1048782016
- V38M (p.Val38Met), TOPMed rs1048782016, REVEL 0.22, CADD 22.90
- P39S (p.Pro39Ser), cosmic curated COSV10588, gnomAD rs1397180409, REVEL 0.27, CADD 17.90
- P39T (p.Pro39Thr), gnomAD 2-154698890-C-A, REVEL 0.27, CADD 18.80
- K40N (p.Lys40Asn), NCI-TCGA Cosmic COSV5453, NCI-TCGA Cosmic COSV9971, cosmic curated COSV99716, REVEL 0.38, CADD 23.00, Variant assessed as somatic; moderate impact.
- K40R (p.Lys40Arg), rs16838016, cosmic curated COSV54543, UniProt VAR 049669, 1000Genomes rs16838016, REVEL 0.28, CADD 20.20
- K40Q (p.Lys40Gln), gnomAD 2-154698893-A-C, REVEL 0.29, CADD 24.20
- K40K (p.Lys40Lys), rs1684836645, gnomAD 2-154698895-G-A, CADD 10.50
- K41K (p.Lys41Lys), rs749684017, gnomAD 2-154698898-G-A, CADD 12.30
- K42N (p.Lys42Asn), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54537, Variant assessed as somatic; moderate impact.
- R43W (p.Arg43Trp), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99716, Variant assessed as somatic; moderate impact.
- R43Q (p.Arg43Gln), gnomAD 2-154698903-G-A, REVEL 0.36, CADD 24.70
- R43R (p.Arg43Arg), gnomAD 2-154698904-G-A, CADD 13.00
- Q44Q (p.Gln44Gln), gnomAD 2-154698907-G-A, CADD 11.40
- R45L (p.Arg45Leu), cosmic curated COSV54533, ExAC rs771489524, gnomAD rs771489524, REVEL 0.85, CADD 29.00
- R45R (p.Arg45Arg), rs1684836837, gnomAD 2-154698908-C-A, CADD 13.20
- F46S (p.Phe46Ser), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54539, Variant assessed as somatic; moderate impact.
- F46V (p.Phe46Val), Ensembl rs1574424617
- V47A (p.Val47Ala), TOPMed rs1323586199, gnomAD rs1323586199, REVEL 0.94, CADD 29.40
- V47L (p.Val47Leu), gnomAD 2-154698914-G-T, REVEL 0.90, CADD 27.50
- V47V (p.Val47Val), gnomAD 2-154698916-G-A, CADD 13.00
- N50K (p.Asn50Lys), cosmic curated COSV99039, Ensembl rs1574424629
- G51D (p.Gly51Asp), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99716, Variant assessed as somatic; moderate impact.
- G51G (p.Gly51Gly), rs774843395, gnomAD 2-154698928-C-G, CADD 13.70
- R52L (p.Arg52Leu), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, Variant assessed as somatic; moderate impact.
- R52Q (p.Arg52Gln), NCI-TCGA Cosmic COSV9971, Ensembl rs1684837726, Variant assessed as somatic; moderate impact.
- R52W (p.Arg52Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C53G (p.Cys53Gly), Ensembl rs1574424637, REVEL 0.96, CADD 31.00
- N54N (p.Asn54Asn), rs759888188, gnomAD 2-154698937-T-C, CADD 14.00
- V55L (p.Val55Leu), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54530, Variant assessed as somatic; moderate impact.
- V55V (p.Val55Val), rs1684837944, gnomAD 2-154698940-A-G, CADD 3.58
- Q56K (p.Gln56Lys), NCI-TCGA Cosmic COSV5454, cosmic curated COSV54540, Variant assessed as somatic; moderate impact.
- Q56R (p.Gln56Arg), gnomAD 2-154698942-A-G, REVEL 0.64, CADD 23.00
- Q56Q (p.Gln56Gln), rs767606154, gnomAD 2-154698943-G-A, CADD 11.60
- G58C (p.Gly58Cys), TOPMed rs1324602706, gnomAD rs1324602706, REVEL 0.87, CADD 29.30
- G58D (p.Gly58Asp), NCI-TCGA Cosmic COSV9971, Variant assessed as somatic; moderate impact.
- G58R (p.Gly58Arg), TOPMed rs1324602706, gnomAD rs1324602706, REVEL 0.84, CADD 28.90
- G58V (p.Gly58Val), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, Variant assessed as somatic; moderate impact.
- G58S (p.Gly58Ser), gnomAD 2-154698947-G-A, REVEL 0.75, CADD 25.00
- G58G (p.Gly58Gly), rs775672678, gnomAD 2-154698949-C-A, CADD 12.10
- N59D (p.Asn59Asp), gnomAD 2-154698950-A-G, REVEL 0.92, CADD 29.20
- L60L (p.Leu60Leu), gnomAD 2-154698953-C-T, CADD 13.30
- L60P (p.Leu60Pro), gnomAD 2-154698954-T-C, REVEL 0.95, CADD 32.00
- G61D (p.Gly61Asp), Ensembl rs1558849082
- G61R (p.Gly61Arg), gnomAD 2-154698956-G-C, REVEL 0.67, CADD 26.00
- G61G (p.Gly61Gly), gnomAD 2-154698958-C-T, CADD 13.70
- S62G (p.Ser62Gly), rs2468862815, ClinGen CA348676135, ClinVar RCV004406226, Uncertain significance, not specified
- S62N (p.Ser62Asn), Ensembl rs1684838345
- S62S (p.Ser62Ser), rs369723857, gnomAD 2-154698961-C-T, CADD 14.30
- E63Q (p.Glu63Gln), cosmic curated COSV10732, TOPMed rs1392113942, REVEL 0.79, CADD 24.30
- E63E (p.Glu63Glu), rs750265589, gnomAD 2-154698964-G-A, CADD 10.30
- T64K (p.Thr64Lys), ExAC rs758323912, gnomAD rs758323912, REVEL 0.55, CADD 18.50
- T64T (p.Thr64Thr), gnomAD 2-154698967-A-G, CADD 6.60
- S65S (p.Ser65Ser), gnomAD 2-154698970-C-T, CADD 13.80
- R66C (p.Arg66Cys), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54536, Variant assessed as somatic; moderate impact.
- R66H (p.Arg66His), cosmic curated COSV10882, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y67F (p.Tyr67Phe), gnomAD 2-154698975-A-T, REVEL 0.61, CADD 23.20
- Y67Y (p.Tyr67Tyr), rs1457756210, gnomAD 2-154698976-C-T, CADD 11.80
- L68F (p.Leu68Phe), ExAC rs766216456, TOPMed rs766216456, gnomAD rs766216456, REVEL 0.48, CADD 23.80
- L68L (p.Leu68Leu), gnomAD 2-154698979-C-G, CADD 10.10
- S69L (p.Ser69Leu), NCI-TCGA Cosmic COSV5453, NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, Variant assessed as somatic; moderate impact.
- S69W (p.Ser69Trp), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54533, NCI-TCGA Cosmic COSV9971, Variant assessed as somatic; moderate impact.
- D70N (p.Asp70Asn), rs867432352, NCI-TCGA Cosmic COSV5453, cosmic curated COSV54534, Variant assessed as somatic; moderate impact.
- D70Y (p.Asp70Tyr), NCI-TCGA Cosmic COSV5453, cosmic curated COSV54538, Variant assessed as somatic; moderate impact.
- L71F (p.Leu71Phe), TOPMed rs1684838924, REVEL 0.59, CADD 23.60
- T74T (p.Thr74Thr), rs751330548, gnomAD 2-154698997-G-T, CADD 8.65
- L75R (p.Leu75Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L75L (p.Leu75Leu), rs1156634063, gnomAD 2-154698998-C-T, CADD 12.80
- V76L (p.Val76Leu), TOPMed rs1468753141
- L78F (p.Leu78Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K79N (p.Lys79Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K79Q (p.Lys79Gln), NCI-TCGA Cosmic COSV5454, cosmic curated COSV54545, REVEL 0.80, CADD 23.10, Variant assessed as somatic; moderate impact.
- K79R (p.Lys79Arg), TOPMed rs1684839203, gnomAD rs1684839203, REVEL 0.64, CADD 23.00
- R81S (p.Arg81Ser), TOPMed rs1379622517
- R81H (p.Arg81His), gnomAD 2-154699017-G-A, REVEL 0.85, CADD 26.00
- R81L (p.Arg81Leu), gnomAD 2-154699017-G-T, REVEL 0.93, CADD 26.20
- W82R (p.Trp82Arg), NCI-TCGA Cosmic COSV5454, cosmic curated COSV54543, Variant assessed as somatic; moderate impact.
- L84F (p.Leu84Phe), rs1029458808, ClinGen CA348676287, ClinVar RCV004406227, TOPMed rs1029458808, Uncertain significance, not specified
- L84V (p.Leu84Val), cosmic curated COSV54537, TOPMed rs1029458808, gnomAD rs1029458808, REVEL 0.77, CADD 23.00, Uncertain significance
- L84L (p.Leu84Leu), gnomAD 2-154699027-C-A, CADD 12.60
- F85I (p.Phe85Ile), TOPMed rs1684839416, REVEL 0.36, CADD 23.20
- F85S (p.Phe85Ser), gnomAD 2-154699029-T-C, REVEL 0.71, CADD 26.20
- F85L (p.Phe85Leu), gnomAD 2-154699030-C-A, REVEL 0.29, CADD 16.90
- I86T (p.Ile86Thr), NCI-TCGA TCGA novel, REVEL 0.90, CADD 29.00, Variant assessed as somatic; moderate impact.
- I88V (p.Ile88Val), gnomAD rs1684839490, REVEL 0.24, CADD 17.60
- I88I (p.Ile88Ile), gnomAD 2-154699039-T-C, CADD 12.40
- L89F (p.Leu89Phe), Ensembl rs955382991
- L89L (p.Leu89Leu), rs2105142681, gnomAD 2-154699042-C-T, CADD 12.40
- T90I (p.Thr90Ile), gnomAD rs1214440777, REVEL 0.37, CADD 25.20
- V93E (p.Val93Glu), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99716, Variant assessed as somatic; moderate impact.
- V93L (p.Val93Leu), gnomAD 2-154699052-G-T, REVEL 0.33, CADD 22.40
- A94T (p.Ala94Thr), Ensembl rs1684839729
- A94A (p.Ala94Ala), rs754662868, gnomAD 2-154699057-C-T, CADD 14.70
- W95* (p.Trp95Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L96H (p.Leu96His), gnomAD 2-154699062-T-A, REVEL 0.95, CADD 31.00
- L96L (p.Leu96Leu), rs2105142697, gnomAD 2-154699063-T-C, CADD 13.90
- F97I (p.Phe97Ile), gnomAD 2-154699064-T-A, REVEL 0.49, CADD 22.80
- F97F (p.Phe97Phe), rs780666205, gnomAD 2-154699066-C-T, CADD 14.50
- M98T (p.Met98Thr), cosmic curated COSV54538, ExAC rs747717603, gnomAD rs747717603, REVEL 0.95, CADD 27.40
- A99E (p.Ala99Glu), NCI-TCGA Cosmic COSV5454, Variant assessed as somatic; moderate impact.
- A99V (p.Ala99Val), NCI-TCGA Cosmic COSV5454, cosmic curated COSV54546, Variant assessed as somatic; moderate impact.
- A99A (p.Ala99Ala), rs755521421, gnomAD 2-154699072-G-T, CADD 13.50
- W102C (p.Trp102Cys), gnomAD rs1474925551, REVEL 0.96, CADD 32.00
- W103C (p.Trp103Cys), NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, Variant assessed as somatic; moderate impact.
- V104A (p.Val104Ala), TOPMed rs1191234143, gnomAD rs1191234143, REVEL 0.40, CADD 24.20
- V104G (p.Val104Gly), TOPMed rs1191234143, gnomAD rs1191234143
- I105M (p.Ile105Met), NCI-TCGA Cosmic COSV5454, NCI-TCGA Cosmic COSV9971, cosmic curated COSV99715, Variant assessed as somatic; moderate impact.
- I105I (p.Ile105Ile), rs777333112, gnomAD 2-154699090-C-T, CADD 14.00
Public KCNJ3 analysis runs
- KCNJ3 analysis run — KCNJ3 (890 variants) — completed 2026-08-22