ASIC4

protein-coding

acid sensing ion channel subunit family member 4, the group of Acid sensing ion channel subunits

Gene summary

This gene belongs to the superfamily of acid-sensing ion channels, which are proton-gated, amiloride-sensitive sodium channels. These channels have been implicated in synaptic transmission, pain perception as well as mechanoperception. This gene is predominantly expressed in the pituitary gland, and was considered a candidate for paroxysmal dystonic choreoathetosis (PDC), a movement disorder, however, no correlation was found between mutations in this gene and PDC. [provided by RefSeq, Feb 2012]

Previous symbols:

ACCN4

MANE transcript

NM_018674.6

Inheritance

—

ClinVar variants

U:1B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr2:219,514,170-219,538,772

External References & Databases

Ensembl (ENSG00000072182)

Transcript & Mutation Effects

hg38 • Region Span ~24.6 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 ASIC4 variants in ClinVar

1 Conditions Cataloged

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018674.6. 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				2 clinvar	3 clinvar	5
missense			1 clinvar	1 clinvar	1 clinvar	3
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	1	3	4	8

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018674.6	RefSeq	NP_061144.4	10	MANE Select
ENST00000358078.5	Ensembl	ENSP00000350786.5	10	MANE Select
NM_182847.3	RefSeq	NP_878267.3	9	Standard
ENST00000347842.8	Ensembl	ENSP00000326627.4	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Stimuli-sensing channels
Ion channel transport
Transport of small molecules

Biological Process

behavioral fear response
sodium ion transmembrane transport

Molecular Function

ion channel activity
sodium channel activity
sodium ion transmembrane transporter activity

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000347842
Coding exons: 9
Length: 24603
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125747
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.751	364	407	0.895	0.0000252	4104
Missense (PolyPhen)		92	142.49	0.64567		1401
Synonymous	-0.620	182	172	1.06	0.0000102	1390
Loss of Function	3.04	9	25.6	0.352	0.00000134	271

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0.000097	0.000092	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable cation channel with high affinity for sodium. In vitro, has no proton-gated channel activity. {ECO:0000269|PubMed:10852210}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

RVIS EVS: 0.4
RVIS percentile EVS: 76.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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