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.

• Hearing loss, autosomal dominant 89 (1 variants)
• Dominant progressive sensorineural hearing loss (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			42		3	45
nonsense						0
start loss						0
frameshift	1	1	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	1	43	0	4

Variants in ATOH1

This is a list of pathogenic ClinVar variants found in the ATOH1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-93828948-G-C		not specified	Uncertain significance (Dec 19, 2022)
4-93828983-C-A		not specified	Uncertain significance (Mar 11, 2022)
4-93828999-C-G		ATOH1-related disorder	Uncertain significance (Sep 04, 2024)
4-93828999-C-T		not specified	Uncertain significance (Sep 16, 2021)
4-93829059-G-C		not specified	Uncertain significance (Jul 13, 2021)
4-93829061-G-A		ATOH1-related disorder	Likely benign (Jun 26, 2019)
4-93829075-C-T		not specified	Uncertain significance (Mar 14, 2023)
4-93829076-G-A		ATOH1-related disorder	Benign (Dec 09, 2019)
4-93829105-A-T		not specified	Uncertain significance (Dec 27, 2023)
4-93829113-G-A		not specified	Uncertain significance (Apr 12, 2022)
4-93829144-G-A		Hearing loss, autosomal dominant 89	Uncertain significance (Sep 05, 2024)
4-93829180-C-T		not specified	Uncertain significance (Oct 26, 2021)
4-93829209-C-T		ATOH1-related disorder • not specified	Uncertain significance (Jan 12, 2024)
4-93829213-G-T		not specified	Uncertain significance (Jun 01, 2023)
4-93829218-G-A		not specified	Uncertain significance (Jan 18, 2025)
4-93829228-G-C		not specified	Uncertain significance (Oct 16, 2024)
4-93829252-G-A		not specified	Uncertain significance (Feb 28, 2023)
4-93829256-C-A		not specified	Uncertain significance (May 08, 2024)
4-93829264-C-T		not specified	Uncertain significance (Jan 10, 2022)
4-93829340-C-G		ATOH1-related disorder	Benign (Jun 27, 2018)
4-93829344-C-A		not specified	Uncertain significance (Sep 24, 2024)
4-93829357-G-A		not specified	Uncertain significance (Dec 04, 2023)
4-93829368-C-T		ATOH1-related disorder	Uncertain significance (Feb 13, 2024)
4-93829392-G-T		not specified	Uncertain significance (Dec 27, 2023)
4-93829407-C-G		Pontoneocerebellar hypoplasia;Global developmental delay;Hearing loss • See cases	Uncertain significance (May 02, 2020)

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
0.0178	0.902	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

Haploinsufficiency Scores

• pHI: 0.768
• hipred: Y
• hipred_score: 0.694
• ghis: 0.403

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

Mouse Genome Informatics

• Gene name: Atoh1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

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