ATOH8

atonal bHLH transcription factor 8, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 2:85751344-85791383

Links

ENSG00000168874 ∙ NCBI:84913 ∙ OMIM:619820 ∙ HGNC:24126 ∙ Uniprot:Q96SQ7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATOH8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATOH8 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						0
missense			27	1		28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	1	0

Variants in ATOH8

This is a list of pathogenic ClinVar variants found in the ATOH8 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-85754209-T-C		not specified	Uncertain significance (Apr 04, 2023)
2-85754292-C-G		not specified	Uncertain significance (Dec 15, 2022)
2-85754335-C-G		not specified	Uncertain significance (May 27, 2022)
2-85754378-G-T		not specified	Uncertain significance (Feb 10, 2023)
2-85754406-C-A		not specified	Uncertain significance (Nov 08, 2022)
2-85754442-C-T		not specified	Uncertain significance (Dec 14, 2023)
2-85754451-G-A		not specified	Uncertain significance (Feb 13, 2024)
2-85754452-G-T		not specified	Uncertain significance (Feb 14, 2023)
2-85754454-G-C		not specified	Uncertain significance (Sep 29, 2023)
2-85754469-G-A		not specified	Likely benign (Feb 22, 2023)
2-85754475-C-T		not specified	Uncertain significance (Sep 01, 2021)
2-85754490-G-A		not specified	Uncertain significance (Jun 16, 2023)
2-85754496-G-C		not specified	Uncertain significance (Aug 30, 2021)
2-85754520-T-C		not specified	Uncertain significance (Mar 22, 2023)
2-85754527-C-T		not specified	Uncertain significance (Sep 28, 2022)
2-85754553-C-T		not specified	Uncertain significance (Aug 30, 2022)
2-85754562-C-T		not specified	Uncertain significance (Feb 14, 2023)
2-85754581-C-T		not specified	Uncertain significance (Jan 04, 2024)
2-85754611-A-C		not specified	Uncertain significance (Jul 20, 2021)
2-85754643-C-T		not specified	Uncertain significance (Mar 20, 2024)
2-85754665-C-G		not specified	Uncertain significance (May 28, 2024)
2-85754695-C-G		not specified	Uncertain significance (Sep 29, 2022)
2-85754730-C-T		not specified	Uncertain significance (Jul 08, 2022)
2-85754911-C-A		not specified	Uncertain significance (Aug 28, 2023)
2-85754940-G-C		not specified	Uncertain significance (Feb 06, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATOH8	protein_coding	protein_coding	ENST00000306279	3	36723

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.914	0.0855	123167	0	3	123170	0.0000122

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.416	196	180	1.09	0.00000933	1940
Missense in Polyphen		43	57.911	0.74252		575
Synonymous	-0.747	94	85.2	1.10	0.00000440	727
Loss of Function	2.60	0	7.88	0.00	3.45e-7	100

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000707	0.0000662
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000191	0.0000180
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins (PubMed:24236640). Regulates endothelial cell proliferation, migration and tube-like structures formation (PubMed:24463812). Modulates endothelial cell differentiation through NOS3 (PubMed:24463812). May be implicated in specification and differentiation of neuronal cell lineages in the brain (By similarity). May participate in kidney development and may be involved in podocyte differentiation (By similarity). During early embryonic development is involved in tissue-specific differentiation processes that are dependent on class II bHLH factors and namely modulates the differentiation program initiated by the pro-endocrine factor NEUROG3 (By similarity). During myogenesis, may play a role during the transition of myoblasts from the proliferative phase to the differentiation phase (By similarity). Positively regulates HAMP transcription in two ways, firstly by acting directly on the HAMP promoter via E-boxes binding and indirectly through increased phosphorylation of SMAD protein complex (PubMed:24236640). Repress NEUROG3-dependent gene activation in a gene-specific manner through at least two mechanisms; requires only either the sequestering of a general partner such as TCF3 through heterodimerization, either also requires binding of the bHLH domain to DNA via a basic motif (By similarity). {ECO:0000250|UniProtKB:Q99NA2, ECO:0000269|PubMed:24236640, ECO:0000269|PubMed:24463812}.

Recessive Scores

• pRec: 0.119

Haploinsufficiency Scores

• pHI: 0.569
• hipred: Y
• hipred_score: 0.617
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.406

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atoh8
• 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)

Zebrafish Information Network

• Gene name: atoh8
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: formation of primary germ layer;negative regulation of endothelial cell proliferation;nervous system development;positive regulation of endothelial cell migration;negative regulation of gene expression;cell differentiation;tube formation;positive regulation of endothelial cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;myoblast proliferation;SMAD protein signal transduction;positive regulation of pri-miRNA transcription by RNA polymerase II
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear speck
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;activating transcription factor binding;protein dimerization activity;E-box binding