KCNIP4
protein-codingpotassium voltage-gated channel interacting protein 4, the group of MicroRNA protein coding host genes|EF-hand domain containing|Potassium voltage-gated channel regulatory subunits
Gene summary
This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. This protein member also interacts with presenilin. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1,220.2 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 KCNIP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_025221.6. 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 | 0 | |||||
| missense | 16 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 19 | 0 | 0 | 19 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079497.2 | 9 | MANE Select | |
| Ensembl | ENSP00000371587.2 | 9 | MANE Select | |
| RefSeq | NP_001030175.1 | 8 | Standard | |
| RefSeq | NP_001030176.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Phase 1 - inactivation of fast Na+ channels
- Cardiac conduction
- Muscle contraction
- Regulation of nuclear beta catenin signaling and target gene transcription
Biological Process
- potassium ion transmembrane transport
- protein localization to plasma membrane
- regulation of potassium ion transmembrane transport
Molecular Function
- voltage-gated ion channel activity
- potassium channel activity
- calcium ion binding
- protein binding
- potassium channel regulator activity
Cellular Component
- cytoplasm
- endoplasmic reticulum
- cytosol
- plasma membrane
- voltage-gated potassium channel complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382152
- Coding exons
- 9
- Length
- 1220184
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125707
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.39 | 94 | 140 | 0.669 | 0.00000754 | 1688 |
| Missense (PolyPhen) | 24 | 50.672 | 0.47364 | 635 | ||
| Synonymous | 0.0220 | 49 | 49.2 | 0.996 | 0.00000288 | 429 |
| Loss of Function | 3.03 | 2 | 14.4 | 0.139 | 6.10e-7 | 182 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000063 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Modulates KCND2 channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner (PubMed:11847232, PubMed:18957440, PubMed:23576435). Modulates KCND3/Kv4.3 currents (PubMed:23576435). Isoform 4 does not increase KCND2 expression at the cell membrane (PubMed:18957440). Isoform 4 retains KCND3 in the endoplasmic reticulum and negatively regulates its expression at the cell membrane. {ECO:0000250|UniProtKB:Q6PHZ8, ECO:0000269|PubMed:11847232, ECO:0000269|PubMed:18957440, ECO:0000269|PubMed:23576435}.;
Intolerance Scores
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.943
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |