KCNIP1

protein-coding

potassium voltage-gated channel interacting protein 1, the group of EF-hand domain containing|Potassium voltage-gated channel regulatory subunits

Gene summary

This gene encodes a member of the family of cytosolic voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the neuronal calcium sensor (NCS) family of the calcium binding EF-hand proteins. They associate with Kv4 alpha subunits to form native Kv4 channel complexes. The encoded protein may regulate rapidly inactivating (A-type) currents, and hence neuronal membrane excitability, in response to changes in the concentration of intracellular calcium. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

MANE transcript

NM_014592.4

Inheritance

—

ClinVar variants

P:1U:16B:1

Top phenotype

Idiopathic generalized epilepsy

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr5:170,353,487-170,736,632

External References & Databases

Ensembl (ENSG00000182132)

Transcript & Mutation Effects

hg38 • Region Span ~383.1 kb

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GenCC 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 KCNIP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 17

Idiopathic generalized epilepsyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014592.4. 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	1 clinvar		15 clinvar	1 clinvar		17
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	16	1	0	18

Highest pathogenic variant AF is 0.0000012433899

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014592.4	RefSeq	NP_055407.1	8	MANE Select
ENST00000328939.9	Ensembl	ENSP00000329686.4	8	MANE Select
NM_001034837.3	RefSeq	NP_001030009.1	9	Standard
NM_001034838.3	RefSeq	NP_001030010.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
kcnip1a	Danio rerio	Structure: otolith Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

kcnip1a

Danio rerio

Structure: otolith

Quality: morphology

abnormal

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

Biological Process

potassium ion transmembrane transport
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
plasma membrane
voltage-gated potassium channel complex
dendrite
extrinsic component of cytoplasmic side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000411494
Coding exons: 9
Length: 383146
Individuals with no LoFs: 125683
Homozygous LoFs: 0
Heterozygous LoFs: 65
Defined: 125748
p: 0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.66	79	133	0.595	0.00000723	1525
Missense (PolyPhen)		25	65.188	0.38351		754
Synonymous	0.862	45	53.0	0.849	0.00000356	382
Loss of Function	2.37	7	17.8	0.393	9.06e-7	195

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00040	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0022	0.0022	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Regulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. In vitro, modulates KCND1/Kv4.1 and KCND2/Kv4.2 currents. Increases the presence of KCND2 at the cell surface. {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:11423117, ECO:0000269|PubMed:12829703, ECO:0000269|PubMed:17187064}.;

Recessive Scores

pRec: 0.136

Intolerance Scores

LoFtool: 0.440
RVIS EVS: -0.01
RVIS percentile EVS: 53.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium