KCNH7

protein-coding

potassium voltage-gated channel subfamily H member 7, the group of PAS domain containing|Potassium voltage-gated channels

Gene summary

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, subfamily H. This member is a pore-forming (alpha) subunit. There are at least two alternatively spliced transcript variants derived from this gene and encoding distinct isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_033272.4

Inheritance

ClinVar variants

U:107B:18

Top phenotype

KCNH7-related disorder

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr2:162,371,407-162,838,767

External References & Databases

Ensembl (ENSG00000184611)

Transcript & Mutation Effects

hg38 • Region Span ~467.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epilepsyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005027

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCNH7 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 104

KCNH7-related disorderTotal: 11

not providedTotal: 6

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033272.4. 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			2 clinvar	7 clinvar	2 clinvar	11
missense			104 clinvar	6 clinvar	3 clinvar	113
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	107	13	5	125

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033272.4	RefSeq	NP_150375.2	16	MANE Select
ENST00000332142.10	Ensembl	ENSP00000331727.5	16	MANE Select
NM_173162.3	RefSeq	NP_775185.1	8	Standard
ENST00000328032.8	Ensembl	ENSP00000333781.4	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuronal System
Voltage gated Potassium channels
Potassium Channels

Biological Process

regulation of ion transmembrane transport
regulation of membrane potential
potassium ion transmembrane transport

Molecular Function

voltage-gated potassium channel activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000332142
Coding exons: 16
Length: 467324
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.04	426	643	0.663	0.0000332	7869
Missense (PolyPhen)		86	236.8	0.36317		2897
Synonymous	-1.15	263	240	1.09	0.0000132	2307
Loss of Function	5.35	13	56.4	0.231	0.00000343	652

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000082	0.000079	rare
South Asian	0.00014	0.00013	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium channel. Channel properties may be modulated by cAMP and subunit assembly.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.0506
RVIS EVS: -0.31
RVIS percentile EVS: 32.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.409

Gene Damage Prediction

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