KCND1

protein-coding

potassium voltage-gated channel subfamily D member 1, the group of Potassium voltage-gated channels

Gene summary

This gene encodes a multipass membrane protein that comprises the pore subunit of the voltage-gated A-type potassium channel, which functions in the repolarization of membrane action potentials. Activity of voltage-gated potassium channels is important in a number of physiological processes, among them the regulation of neurotransmitter release, heart rate, insulin secretion, and smooth muscle contraction. [provided by RefSeq, Aug 2013]

MANE transcript

NM_004979.6

Inheritance

ClinVar variants

U:101B:8

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chrX:48,960,982-48,971,844

External References & Databases

Ensembl (ENSG00000102057)

Transcript & Mutation Effects

hg38 • Region Span ~10.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCND1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 21

Short statureTotal: 2

KCND1-associated seizure disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004979.6. 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			1 clinvar	4 clinvar	1 clinvar	6
missense			97 clinvar	1 clinvar	2 clinvar	100
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	101	5	3	109

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004979.6	RefSeq	NP_004970.3	6	MANE Select
ENST00000218176.4	Ensembl	ENSP00000218176.3	6	MANE Select
ENST00000376477.5	Ensembl	ENSP00000365660.1	5	Standard
ENST00000376477.6	Ensembl	ENSP00000365660.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuronal System
Phase 1 - inactivation of fast Na+ channels
Cardiac conduction
Muscle contraction
Voltage gated Potassium channels

Biological Process

regulation of ion transmembrane transport
protein homooligomerization
potassium ion transmembrane transport

Molecular Function

voltage-gated potassium channel activity
metal ion binding

Cellular Component

cellular_component
plasma membrane
voltage-gated potassium channel complex
integral component of membrane
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000218176
Coding exons: 6
Length: 9338
Individuals with no LoFs: 125728
Homozygous LoFs: 4
Heterozygous LoFs: 5
Defined: 125737
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.93	216	312	0.693	0.0000293	4181
Missense (PolyPhen)		60	107.02	0.56062		1461
Synonymous	0.583	122	130	0.935	0.0000122	1403
Loss of Function	2.83	4	16.3	0.245	0.00000140	226

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	0.0	absent
Finnish	0.00013	0.000092	rare
European (Non-Finnish)	0.000049	0.000035	rare
South Asian	0.00017	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.0570
RVIS EVS: -0.18
RVIS percentile EVS: 40.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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