ASIC2
protein-codingacid sensing ion channel subunit 2, the group of Acid sensing ion channel subunits
Gene summary
This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, 2 hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene may play a role in neurotransmission. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 3 has been observed to co-assemble into proton-gated channels sensitive to gadolinium. Alternative splicing has been observed at this locus and two variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Feb 2012]
- ACCN
- ACCN1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1,161.9 kbGenCC 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 ASIC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_183377.2. 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 | 1 | 1 | 4 | ||
| missense | 70 | 70 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 75 | 1 | 1 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_899233.1 | 10 | MANE Select | |
| Ensembl | ENSP00000225823.2 | 10 | MANE Select | |
| RefSeq | NP_001085.2 | 10 | Standard | |
| Ensembl | ENSP00000352934.6 | 10 | 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)
- Taste transduction - Homo sapiens (human)
- Stimuli-sensing channels
- Ion channel transport
- Transport of small molecules
Biological Process
- regulation of systemic arterial blood pressure by aortic arch baroreceptor feedback
- chemical synaptic transmission
- central nervous system development
- peripheral nervous system development
- phototransduction
Molecular Function
- protein binding
- ligand-gated sodium channel activity
- acid-sensing ion channel activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- neuronal cell body
- dendritic spine
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000225823
- Coding exons
- 10
- Length
- 1161879
- Individuals with no LoFs
- 125739
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125748
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.67 | 217 | 298 | 0.728 | 0.0000147 | 3613 |
| Missense (PolyPhen) | 68 | 130.27 | 0.522 | 1502 | ||
| Synonymous | 0.870 | 113 | 125 | 0.901 | 0.00000665 | 1114 |
| Loss of Function | 4.43 | 1 | 24.8 | 0.0404 | 0.00000124 | 290 |
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 | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Heteromeric channel assembly seems to modulate.;
Recessive Scores
- pRec
- 0.144
Intolerance Scores
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.51
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 |