ATOH1

protein-coding

atonal bHLH transcription factor 1, the group of Basic helix-loop-helix proteins

Gene summary

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including neuron differentiation; positive regulation of neuron differentiation; and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including generation of neurons; inner ear morphogenesis; and positive regulation of inner ear auditory receptor cell differentiation. Predicted to be located in chromatin. Predicted to be active in nucleus. Implicated in autosomal dominant nonsyndromic deafness 89. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_005172.2

Inheritance

AR, AD

ClinVar variants

P:3U:64B:12

Top phenotype

Deafness, autosomal dominant 89

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr4:93,828,753-93,830,964

External References & Databases

Ensembl (ENSG00000172238)

Transcript & Mutation Effects

hg38 • Region Span ~2.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pontocerebellar hypoplasiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020135

Submitter: PanelApp Australia

hearing loss, autosomal dominant 89LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0859528

Submitter: Ambry Genetics

hearing loss, autosomal dominant 89LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0859528

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Deafness, autosomal dominant 89AD

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 33111345

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATOH1 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 58

ATOH1-related disorderTotal: 23

not providedTotal: 7

Hearing loss, autosomal dominant 89Total: 2

Dominant progressive sensorineural hearing lossTotal: 1

Pontoneocerebellar hypoplasiaTotal: 1

Hearing lossTotal: 1

Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005172.2. 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				5 clinvar	2 clinvar	7
missense			63 clinvar	2 clinvar	3 clinvar	68
nonsense						0
start loss						0
frameshift	1 clinvar	2 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)						0
Total	1	2	64	7	5	79

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005172.2	RefSeq	NP_005163.1	1	MANE Select
ENST00000306011.6	Ensembl	ENSP00000302216.4	1	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
atoh1a	Danio rerio	Structure: neuromast hair cell Quality: absent abnormal

Gene / Model

Organism

Observed Phenotype

atoh1a

Danio rerio

Structure: neuromast hair cell

Quality: absent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

neuron migration
transcription by RNA polymerase II
Notch signaling pathway
axon guidance
central nervous system development

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA-binding transcription factor activity
chromatin DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306011
Coding exons: 1
Length: 1180
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.134	215	210	1.03	0.00000942	2273
Missense (PolyPhen)		66	82.323	0.80172		933
Synonymous	-1.46	113	94.9	1.19	0.00000446	768
Loss of Function	1.48	4	8.70	0.460	3.70e-7	99

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	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional regulator. Activates E box-dependent transcription in collaboration with TCF3/E47, but the activity is completely antagonized by the negative regulator of neurogenesis HES1. Plays a role in the differentiation of subsets of neural cells by activating E box-dependent transcription (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.283

Intolerance Scores

RVIS EVS: -0.11
RVIS percentile EVS: 45.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.577

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium