KCNH3

protein-coding

potassium voltage-gated channel subfamily H member 3, the group of Potassium voltage-gated channels|PAS domain containing

Gene summary

The protein encoded by this gene is a voltage-gated potassium channel alpha subunit predominantly expressed in the forebrain. Studies in mice have found that cognitive function increases when this gene is knocked out. In humans, the encoded protein has been shown to be capable of binding glycoprotein 120 of the human immunodeficiency virus type 1 (HIV-1) envelope. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

MANE transcript

NM_012284.3

Inheritance

ClinVar variants

U:121B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr12:49,539,030-49,558,337

External References & Databases

Ensembl (ENSG00000135519)

Transcript & Mutation Effects

hg38 • Region Span ~19.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCNH3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012284.3. 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			1 clinvar	1 clinvar	4 clinvar	6
missense			119 clinvar	5 clinvar		124
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	121	6	4	131

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012284.3	RefSeq	NP_036416.1	15	MANE Select
ENST00000257981.7	Ensembl	ENSP00000257981.5	15	MANE Select
NM_001314030.2	RefSeq	NP_001300959.1	14	Standard
ENST00000649994.1	Ensembl	ENSP00000497890.1	4	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

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

Molecular Function

voltage-gated potassium channel activity
protein binding

Cellular Component

plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257981
Coding exons: 15
Length: 19152
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	3.85	403	687	0.587	0.0000427	6851
Missense (PolyPhen)		60	233	0.25751		2412
Synonymous	0.694	291	306	0.950	0.0000196	2403
Loss of Function	5.34	5	42.6	0.117	0.00000223	447

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00016	0.00014	rare
European (Non-Finnish)	0.000072	0.000062	rare
South Asian	0.000070	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits an outward current with fast inactivation. Channel properties may be modulated by cAMP and subunit assembly.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.0322
RVIS EVS: -0.88
RVIS percentile EVS: 10.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.287

Gene Damage Prediction

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