KCNJ12
protein-codingpotassium inwardly rectifying channel subfamily J member 12, the group of Potassium inwardly rectifying channel subfamily J
Gene summary
This gene encodes an inwardly rectifying K+ channel which may be blocked by divalent cations. This protein is thought to be one of multiple inwardly rectifying channels which contribute to the cardiac inward rectifier current (IK1). The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]
- KCNJN1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KCNJ12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021012.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 11 | 4 | 16 | ||
| missense | 69 | 1 | 8 | 78 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 70 | 12 | 12 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066292.2 | 1 | MANE Select | |
| Ensembl | ENSP00000463778.1 | 1 | MANE Select | |
| Ensembl | ENSP00000328150.5 | 1 | Standard | |
| Ensembl | ENSP00000328150.5 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Oxytocin signaling pathway - Homo sapiens (human)
- Cholinergic synapse - Homo sapiens (human)
- Neuronal System
- Phase 4 - resting membrane potential
- Cardiac conduction
Biological Process
- potassium ion transport
- muscle contraction
- regulation of heart contraction
- regulation of ion transmembrane transport
- protein homotetramerization
Molecular Function
- inward rectifier potassium channel activity
- protein binding
- G-protein activated inward rectifier potassium channel activity
Cellular Component
- plasma membrane
- integral component of membrane
- intrinsic component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000583088
- Coding exons
- 1
- Length
- 43671
- Individuals with no LoFs
- 125484
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 264
- Defined
- 125748
- p
- 0.00105
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.16 | 175 | 224 | 0.781 | 0.0000158 | 2494 |
| Missense (PolyPhen) | 74 | 92.981 | 0.79586 | 1092 | ||
| Synonymous | 0.400 | 84 | 88.8 | 0.946 | 0.00000695 | 707 |
| Loss of Function | 1.49 | 3 | 7.35 | 0.408 | 3.29e-7 | 93 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.015 | 0.014 | notable |
| Latino/Admixed American | 0.00046 | 0.00046 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00060 | 0.00060 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inward rectifying potassium channel that is activated by phosphatidylinositol 4,5-bisphosphate and that probably participates in controlling the resting membrane potential in electrically excitable cells. Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. {ECO:0000269|PubMed:12417321, ECO:0000269|PubMed:20921230, ECO:0000269|PubMed:7859381, ECO:0000269|PubMed:8647284}.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- LoFtool
- 0.0599
- RVIS EVS
- 1.56
- RVIS percentile EVS
- 95.67
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.511
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |