ATOH1

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

Basic information

Region (hg38): 4:93828753-93830964

Links

ENSG00000172238 ∙ NCBI:474 ∙ OMIM:601461 ∙ HGNC:797 ∙ Uniprot:Q92858 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal dominant 89 (Limited), mode of inheritance: AD
• hearing loss, autosomal dominant 89 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 89	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	33111345

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATOH1 gene.

• not_specified (58 variants)
• ATOH1-related_disorder (12 variants)
• not_provided (6 variants)
• Hearing_loss,_autosomal_dominant_89 (2 variants)
• Dominant_progressive_sensorineural_hearing_loss (1 variants)
• Pontoneocerebellar_hypoplasia (1 variants)
• Hearing_loss (1 variants)
• Global_developmental_delay (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATOH1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005172.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			62	1	3	66
nonsense						0
start loss						0
frameshift	1	2	1			4
splice donor/acceptor (+/-2bp)						0
Total	1	2	63	3	5

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATOH1	protein_coding	protein_coding	ENST00000306011	1	1180

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.134	215	210	1.03	0.00000942	2273
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.577

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: atoh1a
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: neuron migration;transcription by RNA polymerase II;Notch signaling pathway;axon guidance;central nervous system development;cerebral cortex development;inner ear morphogenesis;auditory receptor cell fate specification;auditory receptor cell fate determination;negative regulation of apoptotic process;positive regulation of inner ear auditory receptor cell differentiation;positive regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• 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;protein dimerization activity