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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ATOH1
atonal bHLH transcription factor 1
Chromosome 4 Β· 4q22.2
NCBI Gene: 474Ensembl: ENSG00000172238.6HGNC: HGNC:797UniProt: Q92858
66PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingpositive regulation of neuron differentiationpositive regulation of transcription by RNA polymerase IIneuron fate commitmenthearing loss, autosomal dominant 89cardiomyopathyaortic diseasecolorectal cancer
✦AI Summary

ATOH1 is a basic helix-loop-helix transcription factor that functions as a key regulator of sensory and secretory cell differentiation. As a transcriptional activator, ATOH1 binds E-box elements and works collaboratively with TCF3/E47 to promote differentiation of specific neural and epithelial cell lineages 1. Its activity is antagonized by the negative regulator HES1, allowing for precise control of cell fate decisions. ATOH1 plays critical roles in multiple tissues. In the intestinal epithelium, ATOH1 directs intestinal stem cell differentiation toward goblet and Paneth cells through the FGF1-FGFR2-TCF4-ATOH1 signaling axis, with goblet cells playing protective roles in inflammatory responses 2. ATOH1 also regulates tuft cell specification, where microbe-derived metabolites like succinate promote tuft cell expansion through ATOH1-dependent mechanisms; tuft cell expansion suppresses ileal inflammation in Crohn's disease models 3. In the inner ear, ATOH1 is essential for hair cell differentiation from pluripotent stem cells, enabling development of functional sensory structures 4. During respiratory system development, ATOH1 contributes to retrotrapezoid nucleus formation, which is critical for central respiratory chemoreception 5. Clinically, ATOH1 dysfunction is associated with deafness, developmental delays, and gastrointestinal pathologies. These findings suggest ATOH1-targeted therapies may benefit patients with hearing loss, inflammatory bowel disease, and regenerative disorders.

Sources cited
1
ATOH1 is a downstream target in the FGF1-FGFR2-TCF4-ATOH1 signaling axis that directs intestinal stem cell differentiation toward goblet cells
PMID: 40188210
2
ATOH1 regulates microbe-metabolite-dependent tuft cell specification; ATOH1-knockout mice have expanded tuft cells, and tuft cell expansion suppresses intestinal inflammation
PMID: 32828819
3
ATOH1 is essential for hair cell induction from human pluripotent stem cells; ATOH1-2A-eGFP labeling enables detection of hair cell differentiation in inner ear organoids
PMID: 28459451
4
ATOH1 is a transcription factor required for retrotrapezoid nucleus development, which is critical for central respiratory chemoreception
PMID: 35965033
5
ATOH1+ secretory cells in intestinal crypts respond to local niche signals; Wnt signaling retains ATOH1+ cells in crypt bottoms while BMPs induce distinct goblet or Paneth phenotypes
PMID: 40203837
6
ATOH1-deficient organoid cultures demonstrated that IL-22-induced epithelial regeneration occurs independently of the Paneth cell niche
PMID: 26649819
7
IL-22Ra1 signaling in MATH1+ (ATOH1+) cells, including goblet and progenitor cells, is essential for mucosal barrier maintenance and intestinal tissue regeneration
PMID: 38733584
Disease Associationsβ“˜21
hearing loss, autosomal dominant 89Open Targets
0.36Weak
cardiomyopathyOpen Targets
0.34Weak
aortic diseaseOpen Targets
0.34Weak
colorectal cancerOpen Targets
0.24Weak
injuryOpen Targets
0.21Weak
prostate carcinomaOpen Targets
0.20Weak
vascular diseaseOpen Targets
0.20Weak
polycystic ovary syndromeOpen Targets
0.19Weak
intelligenceOpen Targets
0.18Weak
obesityOpen Targets
0.18Weak
diabetes mellitusOpen Targets
0.18Weak
attention deficit hyperactivity disorderOpen Targets
0.17Weak
colorectal adenomaOpen Targets
0.16Weak
liver diseaseOpen Targets
0.15Weak
autism spectrum disorderOpen Targets
0.15Weak
acquired thrombocytopeniaOpen Targets
0.14Weak
pontocerebellar hypoplasiaOpen Targets
0.12Weak
Global developmental delayOpen Targets
0.12Weak
Non-syndromic pontocerebellar hypoplasiaOpen Targets
0.12Weak
hearing lossOpen Targets
0.12Weak
Deafness, autosomal dominant, 89UniProt
Pathogenic Variants3
NM_005172.2(ATOH1):c.1024del (p.Ser342fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 342
NM_005172.2(ATOH1):c.901_902dup (p.Leu302fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 302
NM_005172.2(ATOH1):c.1030del (p.His344fs)Pathogenic
Dominant progressive sensorineural hearing loss|Hearing loss, autosomal dominant 89
β˜…β˜†β˜†β˜†2018β†’ Residue 344
View on ClinVar β†—
Related Genes
TCF4Protein interaction91%POU4F3Protein interaction91%BARHL1Protein interaction85%MUC6Protein interaction79%MYO7AProtein interaction79%TCF12Protein interaction76%
Tissue Expression6 tissues
Lung
0%
Brain
0%
Bone Marrow
0%
Heart
0%
Ovary
0%
Liver
0%
Gene Interaction Network
Click a node to explore
ATOH1TCF4POU4F3BARHL1MUC6MYO7ATCF12
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q92858
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.77LoF Tolerant
pLIβ“˜
0.18Tolerant
Observed/Expected LoF0.44 [0.26–0.77]
RankingsWhere ATOH1 stands among ~20K protein-coding genes
  • #7,041of 20,598
    Most Researched66
  • #4,037of 5,498
    Most Pathogenic Variants3
  • #6,197of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedATOH1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration.
PMID: 26649819
Nature Β· 2015
1.00
2
Central respiratory chemoreception.
PMID: 35965033
Handb Clin Neurol Β· 2022
0.90
3
Colonic epithelial-derived FGF1 drives intestinal stem cell commitment toward goblet cells to suppress inflammatory bowel disease.
PMID: 40188210
Nat Commun Β· 2025
0.80
4
Basal cell of origin resolves neuroendocrine-tuft lineage plasticity in cancer.
PMID: 40963028
Nature Β· 2025
0.70
5
Succinate Produced by Intestinal Microbes Promotes Specification of Tuft Cells to Suppress Ileal Inflammation.
PMID: 32828819
Gastroenterology Β· 2020
0.60