KCNIP2
protein-codingpotassium voltage-gated channel interacting protein 2, the group of 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 belongs 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. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified from 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 ~17.9 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 KCNIP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173191.3. 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 | 27 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 27 | 0 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_775283.1 | 10 | MANE Select | |
| Ensembl | ENSP00000349055.2 | 10 | MANE Select | |
| RefSeq | NP_055406.2 | 10 | Standard | |
| RefSeq | NP_775284.1 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antiarrhythmic Pathway, Pharmacodynamics
- Levomethadyl Acetate Action Action Pathway
- Disopyramide Action Pathway
- Procainamide (Antiarrhythmic) Action Pathway
- Phenytoin (Antiarrhythmic) Action Pathway
Biological Process
- detection of calcium ion
- potassium ion transport
- muscle contraction
- signal transduction
- chemical synaptic transmission
Molecular Function
- A-type (transient outward) potassium channel activity
- calcium ion binding
- protein binding
- potassium channel regulator activity
- ion channel binding
Cellular Component
- cytoplasm
- plasma membrane
- voltage-gated potassium channel complex
- potassium channel complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000461105
- Coding exons
- 10
- Length
- 17947
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125744
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.87 | 92 | 158 | 0.581 | 0.00000863 | 1882 |
| Missense (PolyPhen) | 29 | 66.102 | 0.43871 | 767 | ||
| Synonymous | 1.11 | 50 | 61.0 | 0.820 | 0.00000346 | 516 |
| Loss of Function | 2.46 | 6 | 16.9 | 0.355 | 8.19e-7 | 199 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000049 | 0.000046 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Modulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND2/Kv4.2 and KCND3/Kv4.3 currents. Involved in KCND2 and KCND3 trafficking to the cell surface. May be required for the expression of I(To) currents in the heart (By similarity). {ECO:0000250|UniProtKB:Q9JJ69, ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11287421, ECO:0000269|PubMed:11684073, ECO:0000269|PubMed:12297301, ECO:0000269|PubMed:12829703, ECO:0000269|PubMed:14623880}.;
Recessive Scores
- pRec
- 0.155
Intolerance Scores
- LoFtool
- 0.839
- RVIS EVS
- -0.3
- RVIS percentile EVS
- 32.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.469
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |