ATOH1

Chr 4AD

atonal bHLH transcription factor 1

Also known as: ATH1, DFNA89, HATH1, MATH-1, bHLHa14

ATOH1 encodes a transcriptional regulator that activates E box-dependent transcription and plays a critical role in neural cell differentiation, particularly in the development of auditory receptor cells in the inner ear. Mutations cause autosomal dominant nonsyndromic deafness 89, affecting primarily hearing function. The gene shows tolerance to loss-of-function variants (low pLI score), suggesting the pathogenic variants may involve other mechanisms.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Deafness, autosomal dominant 89MIM #620284
AD
0
Active trials
48
Pubs (1 yr)
25
P/LP submissions
0%
P/LP missense
1.05
LOEUF
LOF
Mechanism· predicted
Clinical SummaryATOH1
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 69 VUS of 101 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.05LOEUF
pLI 0.018
Z-score 1.48
OE 0.46 (0.231.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.13Z-score
OE missense 1.03 (0.921.15)
215 obs / 209.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.46 (0.231.05)
00.351.4
Missense OE1.03 (0.921.15)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 4 / 8.7Missense obs/exp: 215 / 209.5Syn Z: -1.46
DN
0.5772th %ile
GOF
0.3887th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

101 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic5
VUS69
Likely Benign3
Benign5
19
Pathogenic
5
Likely Pathogenic
69
VUS
3
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
18
0
19
Likely Pathogenic
2
0
3
0
5
VUS
1
62
6
0
69
Likely Benign
0
1
0
2
3
Benign
0
3
0
2
5
Total466274101

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

View in ClinVar →

Protein Context — Lollipop Plot

ATOH1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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