ASIC3

Chr 7

acid sensing ion channel subunit 3

Also known as: ACCN3, DRASIC, SLNAC1, TNaC1

NCBI Gene: 9311ENSG00000213199UniProt: Q9UHC3

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, two hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene is an acid sensor and may play an important role in the detection of lasting pH changes. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 2 has been observed as proton-gated channels sensitive to gadolinium. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

203
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ASIC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 114 VUS of 203 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.83LOEUF
pLI 0.000
Z-score 2.26
OE 0.54 (0.36–0.83)
Tolerant

Typical tolerance to LoF variation

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.
-0.63Z-score
OE missense 1.09 (1.01–1.19)
387 obs / 353.6 exp
Tolerant

Tolerant to missense variation

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.0.54 (0.36–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (1.01–1.19)
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.1.11
0≤1.21.6
LoF obs/exp: 15 / 27.9Missense obs/exp: 387 / 353.6Syn Z: -1.07

ClinVar Variant Classifications

203 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic4
VUS114
Likely Benign14
Benign2
69
Pathogenic
4
Likely Pathogenic
114
VUS
14
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
69
0
69
Likely Pathogenic
0
0
4
0
4
VUS
1
104
9
0
114
Likely Benign
0
12
1
1
14
Benign
0
2
0
0
2
Total1118831203

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

View in ClinVar →

Protein Context — Lollipop Plot

ASIC3 · 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
Sensing acidosis: nociception or sngception?
Lin JH et al.·J Biomed Sci
2018Review
Acidosis-related pain and its receptors as targets for chronic pain.
Hung CH et al.·Pharmacol Ther
2023Review
Joint Acidosis and Acid-Sensing Receptors and Ion Channels in Osteoarthritis Pathobiology and Therapy.
Martin WN et al.·Cells
2025Review
ASIC3-activated key enzymes of de novo lipid synthesis supports lactate-driven EMT and the metastasis of colorectal cancer cells.
Wan X et al.·Cell Commun Signal
2024
Biomarkers associated with idiopathic frozen shoulder: a systematic review.
Andronic O et al.·Connect Tissue Res
2020Review
Association between an ASIC3 gene variant and insulin resistance in Taiwanese.
Wu S et al.·Clin Chim Acta
2010
Focus on irritable bowel syndrome.
Scalera A et al.·Eur Rev Med Pharmacol Sci
2012Review
Activation of acid-sensing ion channel 3 by lysophosphatidylcholine 16:0 mediates psychological stress-induced fibromyalgia-like pain.
Hung CH et al.·Ann Rheum Dis
2020
Melatonin Plays a Role as a Mediator of Nocturnal Pain in Patients with Shoulder Disorders.
Ha E et al.·J Bone Joint Surg Am
2014Cohort
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
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Short RFamide, CFamide and FCamide peptides as novel positive modulators of ASIC3 with similar potentiating effects but different reversibility.
Toft M et al.·Neuropharmacology
2026
ASIC3-PLCG1 axis-driven macropinocytosis promotes osimertinib drug-tolerant persistence in malignant pleural effusion-associated NSCLC.
Huang WC et al.·Eur J Pharm Sci
2026
Identification, characterization, and structure-activity relationship of the ASIC3-selective peptide WRPRFa.
Chien C et al.·Commun Chem
2025🔓 Open Access
Evidence for acid-sensing ion channel 3 (ASIC3) involvement in cough resulting from aspiration of gastric fluid.
Chou YL et al.·J Physiol
2026
Muscle afferent ASIC3 upregulation mediates the exacerbated exercise pressor reflex in male rats following hindlimb ischemia-reperfusion.
Qin L et al.·Physiol Rep
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

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