ASIC2

Chr 17

acid sensing ion channel subunit 2

Also known as: ACCN, ACCN1, ASIC2a, BNC1, BNaC1, MDEG, hBNaC1

NCBI Gene: 40UniProt: Q16515

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]

105
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· HI
1.7
Missense Z
0.19
LOEUF· LoF intolerant
0
Active trials
Clinical Summary— ASIC2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 91 VUS of 105 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.19LOEUF
pLI 0.999
Z-score 4.43
OE 0.04 (0.01–0.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.67Z-score
OE missense 0.73 (0.65–0.81)
217 obs / 298.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.65–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 1 / 24.8Missense obs/exp: 217 / 298.2Syn Z: 0.87

ClinVar Variant Classifications

105 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS91
Likely Benign3
Benign2
7
Pathogenic
2
Likely Pathogenic
91
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
79
12
0
91
Likely Benign
0
0
2
1
3
Benign
0
0
1
1
2
Total079242105

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ASIC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The acid-sensing ion channel, ASIC2, promotes invasion and metastasis of colorectal cancer under acidosis by activating the calcineurin/NFAT1 axis.
Zhou ZH et al.·J Exp Clin Cancer Res
2017
Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells.
Vila-Carriles WH et al.·J Biol Chem
2007Functional
The role of ASIC2 in glioma progression: implications for prognosis and therapeutic targeting.
Tian W et al.·PeerJ
2026
Acid sensing ion channel 2: A new potential player in the pathophysiology of multiple sclerosis.
Fazia T et al.·Eur J Neurosci
2019
The critical role of calcineurin/NFAT (C/N) pathways and effective antitumor prospect for colorectal cancers.
Gang W et al.·J Cell Biochem
2019Review
Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells.
Vila-Carriles WH et al.·J Biol Chem
2006
Identification of an immune cell infiltration-related gene signature for prognosis prediction in triple-negative breast cancer.
Wang Y et al.·Cell Mol Biol (Noisy-le-grand)
2024
Reduced innervation in the human pharynx in patients with obstructive sleep apnea.
de Carlos F et al.·Histol Histopathol
2015Cohort
ASIC1 and ASIC3 mediate cellular senescence of human nucleus pulposus mesenchymal stem cells during intervertebral disc degeneration.
Ding J et al.·Aging (Albany NY)
2021
Genetic Risk Factors for Bortezomib-induced Neuropathic Pain in an Asian Population: A Genome-wide Association Study in South Korea.
Min YG et al.·J Pain
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The mechanosensitive ion channel ASIC2 mediates both proprioceptive sensing and spinal alignment
Bornstein B et al.·Exp Physiol
2023
Investigating role of ASIC2 in synaptic and behavioral responses to drugs of abuse
Fuller MJ et al.·Front Mol Biosci
2023
Different cervical vertebral bone quality scores for bone mineral density assessment for the patients with cervical degenerative disease undergoing ACCF/ACDF: computed tomography and magnetic resonance imaging-based study
Wang Z et al.·J Orthop Surg Res
2023Cohort
ASIC2 Synergizes with TRPV1 in the Mechano-Electrical Transduction of Arterial Baroreceptors.
Yan X et al.·Neurosci Bull
2021
Pterostilbene alleviates pulmonary fibrosis by regulating ASIC2
Peng Y et al.·Chin Med
2021
A variant of ASIC2 mediates sodium retention in nephrotic syndrome
Fila M et al.·JCI Insight
2021
betaENaC and ASIC2 associate in VSMCs to mediate pressure-induced constriction in the renal afferent arteriole.
Lu Y et al.·Am J Physiol Renal Physiol
2022
Aggressive migration in acidic pH of a glioblastoma cancer stem cell line in vitro is independent of ASIC and KCa3.1 ion channels, but involves phosphoinositide 3-kinase
Cortés Franco KD et al.·Pflugers Arch
2023
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients