ATOH1

Summary

ATOH1 (atonal bHLH transcription factor 1, HGNC:797) is a protein-coding gene on chromosome 4q22.2, encoding Transcription factor ATOH1 (Q92858). Transcriptional regulator.

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; neuroblast migration; 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.

Source: NCBI Gene 474 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 81 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 4
• Transcription factor: yes — 15 downstream targets (CollecTRI)
• MANE Select transcript: NM_005172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:797
Approved symbol	ATOH1
Name	atonal bHLH transcription factor 1
Location	4q22.2
Locus type	gene with protein product
Status	Approved
Aliases	HATH1, MATH-1, Math1, bHLHa14
Ensembl gene	ENSG00000172238
Ensembl biotype	protein_coding
OMIM	601461
Entrez	474

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000306011

RefSeq mRNA: 1 — MANE Select: NM_005172 NM_005172

CCDS: CCDS3638

Canonical transcript exons

ENST00000306011 — 1 exons

Exon	Start	End
ENSE00001175901	93828753	93830964

Expression profiles

Bgee: expression breadth broad, 26 present calls, max score 86.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7391 / max 673.2039, expressed in 63 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48905	0.7184	62
48906	0.0207	7

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	86.24	gold quality
rectum	UBERON:0001052	84.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.98	gold quality
transverse colon	UBERON:0001157	76.66	gold quality
small intestine	UBERON:0002108	74.41	gold quality
mucosa of sigmoid colon	UBERON:0004993	71.30	gold quality
colonic mucosa	UBERON:0000317	70.98	gold quality
ileal mucosa	UBERON:0000331	66.99	silver quality
duodenum	UBERON:0002114	65.86	gold quality
jejunal mucosa	UBERON:0000399	65.80	silver quality
intestine	UBERON:0000160	64.98	gold quality
large intestine	UBERON:0000059	62.17	gold quality
colon	UBERON:0001155	62.03	gold quality
colonic epithelium	UBERON:0000397	61.16	silver quality
vermiform appendix	UBERON:0001154	60.31	gold quality
caecum	UBERON:0001153	57.45	gold quality
biceps brachii	UBERON:0001507	55.63	gold quality
heart right ventricle	UBERON:0002080	55.48	gold quality
nasal cavity epithelium	UBERON:0005384	55.07	gold quality
jejunum	UBERON:0002115	54.29	silver quality
myocardium	UBERON:0002349	54.28	gold quality
germinal epithelium of ovary	UBERON:0001304	52.62	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	52.47	gold quality
quadriceps femoris	UBERON:0001377	50.80	gold quality
vastus lateralis	UBERON:0001379	50.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
deltoid	UBERON:0001476	49.19	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	26.53
E-MTAB-8410	yes	14.26
E-ANND-3	no	1.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

15 targets.

Target	Regulation
ATOH1	Unknown
ATOH7	Activation
BARHL1	Unknown
BARHL2	Activation
BDNF	Unknown
CDH1	Repression
CHRNA1
FGFR1	Repression
HES6	Activation
MUC2	Activation
MUC5AC	Unknown
MUC6	Unknown
NEUROG1	Activation
PCSK6
POU4F3	Unknown

JASPAR motifs

Motif	Name	Family
MA1467.1	ATOH1	Tal-related

JASPAR matrix evidence (PMIDs): PMID:22985730

Upstream regulators (CollecTRI, top): ATOH1, CDX2, CTNNB1, EZH2, H1-4, H4C2, HES1, HES5, HIC1, NEUROD1, NEUROG1, PAX6, SIX1, SOX2, ZIC1

Literature-anchored findings (GeneRIF, showing 40)

• Maps to 10q21-22. Candidate gene for optic nerve aplasia and related syndromes. (PMID:11889557)
• Proneural and proneuroendocrine transcription factor expression in cutaneous mechanoreceptor (Merkel) cells and Merkel cell carcinoma (PMID:12209986)
• Hath1 may regulate the expression of MUC2, a mucin secreted by goblet cells, and Hath1 may also be a novel factor normally repressed as a consequence of activation of the Wnt signaling pathway [review] (PMID:16382053)
• Hath1 is one of the transcriptional regulators for MUC6 and MUC5AC in gastric cancer cells. (PMID:16647036)
• Based on these results, we hypothesize that Cdx2 is involved in activating Math1 expression in intestinal epithelial cells. (PMID:16831200)
• HATH1 is an important factor in the up-regulation of MUC2 expression that occurs in mucinous cancers and signet ring carcinomas. (PMID:17000673)
• GSK3beta-dependent protein degradation was switched between Hath1 and beta-catenin by Wnt signaling, leading to the dramatic alteration of cell status between proliferation and differentiation in colon cancer (PMID:17241872)
• In the chimeric environment, genotypically wild-type cells that possess Math1 have the competence to differentiate into hair cells by providing appropriate environmental interactions. (PMID:17397818)
• Patients with ATOH1-expressing adenocarcinomas might have a worse prognosis. (PMID:17549667)
• ATOH1 activates hairy and enhancer of split 6 transcription through binding to three clustered E boxes of its promoter (PMID:17826772)
• Hath1 protein degradation may be required for maintaining the undifferentiated state of colon cancers, and that GSK3 inhibitors have potential for use in cancer therapy. (PMID:18275842)
• Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation. (PMID:19243219)
• Adult Atoh1-conditional knock-out mice are behaviorally deaf, have diminished auditory brainstem responses and disrupted auditory nuclei morphology. (PMID:19741118)
• we investigated by immunohistochemistry the expression of Hath1 in 63 neuroendocrine tumors (PMID:19924642)
• Atonal homolog 1 is required for growth and differentiation effects of notch/gamma-secretase inhibitors on normal and cancerous intestinal epithelial cells. (PMID:20621629)
• Longitudinal cell formation in the small intestine was regulated by the colocalization of Hath1 and Klf4 that converted Paneth cell differentiation into goblet cell differentiation. (PMID:21125297)
• Math1/Atoh1 ectopic expression significantly reduced cell proliferation and altered cell morphology in Barrett esophagus (PMID:22147253)
• involved in differentiation of neurons, secretory cells in the gut, and mechanoreceptors including auditory hair cells [review] (PMID:22370966)
• In vivo conversion of pillar cells and Deiters’ cells into immature auditory hair cells by Atoh1 is age dependent and resembles normal auditory hair cell development. (PMID:22573682)
• Atoh1 activates cell proliferation within the normally postmitotic cochlear epithelium. (PMID:22573692)
• H. pylori up-regulates Hath1 expression through inducing the release of IL-8 in MKN28 cells. (PMID:22786753)
• Transfection of hATOH1 in combination with hTCF3 or hGATA3 induced 2-3X more Pou4f3/GFP cells, and similarly enhanced Pou4f3/GFP and myosin VIIa double-positive cells, when compared to hATOH1 alone (PMID:22985730)
• Nuclear expression of Atoh1 was inversely correlated with the differentiation and primary tumor stage of lung cancers and also the downregulation of the Wnt pathway. (PMID:23030416)
• the Atoh1 protein regulates malignant potential rather than the differentiation phenotype of mucinous colon cancer (MC), suggesting the mechanism by which MC and signet ring cell carcinoma are more malignant than non-mucinous adenocarcinoma. (PMID:23333391)
• Expression of Hath1, Muc2, cyclin D1 and p27 in the xenograft tumors was also detected. (PMID:23464457)
• The transcription factor Atoh1, which is both necessary and sufficient for hair cell development. (PMID:23724999)
• cotransfection of Pax2 and Math1 strongly stimulates in situ hair cell regeneration in neomycin-damaged cochlear explants. (PMID:24141260)
• Atoh1 transfection drives highly efficient differentiation of human pluripotent stem cells into dopaminergic neurons. (PMID:24904172)
• ATOH1 acts in concert with other transcription factors to directly regulate the cochlear hair cell phenotype. (PMID:25015561)
• Data suggest that Atoh1 high expression correlates with a good prognosis and it may serve as a favorable prognostic factor for GIST. (PMID:25400808)
• Chicken Atoh1 might have intrinsic functional differences to mammalian Atoh1. (PMID:25412697)
• In this review, expression of the Atoh1 gene in supporting cells, results in their transformation into immature hair cells. (PMID:25648190)
• ATOH1 can induce the differentiation of gastric cancer stem cells. (PMID:25950549)
• Testosterone-bovine serum albumin and Math1 treatment could promote an increase in hair-cell like cells in the lesser epithelial ridge through proliferation and transdifferentiation. (PMID:25957791)
• Atoh1 protein stabilization induced both a cancer stem cell phenotype and a mucinous phenotype, resulting in the acquisition of chemoresistance in colorectal cancer (PMID:26017781)
• Atoh1 epigenetic regulation guides hair cell development in the mammalian cochlea (PMID:26487780)
• mutation not found in group of children with sensorineural hearing loss (PMID:26634621)
• Downregulation of Hath1 expression promoted the proliferation and reduced the apoptosis of KUMA5 squamous cell carcinoma cells. (PMID:26648003)
• Study provides evidence that Sox2 expression is required for the late stages of progenitor cell differentiation to hair cells and stimulates Atoh1 expression through a concentration dependent molecular interaction with the 3’ enhancer of Atoh1. (PMID:26988140)
• These data indicate that the regulation of Atoh1 by the ubiquitin proteasome pathway is necessary for hair cell fate determination and survival. (PMID:27542412)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	atoh1a	ENSDARG00000055294
mus_musculus	Atoh1	ENSMUSG00000073043
rattus_norvegicus	Atoh1	ENSRNOG00000006383
drosophila_melanogaster	amos	FBGN0003270
drosophila_melanogaster	ato	FBGN0010433
drosophila_melanogaster	tap	FBGN0015550
caenorhabditis_elegans		WBGENE00003018
caenorhabditis_elegans		WBGENE00003595

Paralogs (15): NEUROG3 (ENSG00000122859), NEUROD4 (ENSG00000123307), BHLHE23 (ENSG00000125533), NEUROD1 (ENSG00000162992), NEUROD6 (ENSG00000164600), ATOH8 (ENSG00000168874), NEUROD2 (ENSG00000171532), OLIG3 (ENSG00000177468), NEUROG2 (ENSG00000178403), ATOH7 (ENSG00000179774), BHLHA15 (ENSG00000180535), BHLHE22 (ENSG00000180828), NEUROG1 (ENSG00000181965), OLIG1 (ENSG00000184221), OLIG2 (ENSG00000205927)

Protein

Protein identifiers

Transcription factor ATOH1 — Q92858 (reviewed: Q92858)

Alternative names: Atonal bHLH transcription factor 1, Class A basic helix-loop-helix protein 14, Helix-loop-helix protein hATH-1, Protein atonal homolog 1

All UniProt accessions (1): Q92858

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein.

Subcellular location. Nucleus.

Disease relevance. Deafness, autosomal dominant, 89 (DFNA89) [MIM:620284] An autosomal dominant form of non-syndromic deafness characterized by progressive hearing loss, with onset at birth or early childhood. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_005163* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR032661	ATOH1_bHLH	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050359	bHLH_transcription_factors	Family

Pfam: PF00010

UniProt features (13 total): compositionally biased region 6, region of interest 4, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92858-F1	60.06	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 172 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, AHRARNT_01, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, HNF3ALPHA_Q6, PAX4_01, CCAWYNNGAAR_UNKNOWN, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, NKX25_02, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (28): neuron migration (GO:0001764), transcription by RNA polymerase II (GO:0006366), Notch signaling pathway (GO:0007219), axon guidance (GO:0007411), central nervous system development (GO:0007417), sensory organ development (GO:0007423), negative regulation of gliogenesis (GO:0014014), central nervous system neuron differentiation (GO:0021953), cerebral cortex development (GO:0021987), inner ear morphogenesis (GO:0042472), auditory receptor cell fate specification (GO:0042667), auditory receptor cell fate determination (GO:0042668), positive regulation of inner ear auditory receptor cell differentiation (GO:0045609), positive regulation of neuron differentiation (GO:0045666), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron fate commitment (GO:0048663), axon development (GO:0061564), neuroblast migration (GO:0097402), epithelial cell apoptotic process (GO:1904019), negative regulation of epithelial cell apoptotic process (GO:1904036), nervous system development (GO:0007399), brain development (GO:0007420), cell differentiation (GO:0030154), inner ear auditory receptor cell differentiation (GO:0042491), regulation of neuron differentiation (GO:0045664), system development (GO:0048731), inner ear development (GO:0048839), positive regulation of inner ear receptor cell differentiation (GO:2000982)

GO Molecular Function (10): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), chromatin DNA binding (GO:0031490), protein dimerization activity (GO:0046983), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron differentiation	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cell migration	2
auditory receptor cell fate commitment	2
regulation of transcription by RNA polymerase II	2
DNA binding	2
generation of neurons	1
DNA-templated transcription	1
cell surface receptor signaling pathway	1
axonogenesis	1
neuron projection guidance	1
nervous system development	1
system development	1
animal organ development	1
regulation of gliogenesis	1
gliogenesis	1
negative regulation of neurogenesis	1
central nervous system development	1
pallium development	1
anatomical structure development	1
ear morphogenesis	1
embryonic morphogenesis	1
inner ear development	1
neuron fate specification	1
neuron fate determination	1
inner ear auditory receptor cell differentiation	1
positive regulation of epidermal cell differentiation	1
regulation of inner ear auditory receptor cell differentiation	1
positive regulation of inner ear receptor cell differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cell fate commitment	1
neuron projection development	1
apoptotic process	1
negative regulation of apoptotic process	1
epithelial cell apoptotic process	1
regulation of epithelial cell apoptotic process	1
chromatin	1

Protein interactions and networks

STRING

1772 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATOH1	BARHL1	Q9BZE3	846
ATOH1	ASCL1	P50553	838
ATOH1	POU4F1	Q01851	820
ATOH1	POU4F3	Q15319	814
ATOH1	MUC6	Q6W4X9	790
ATOH1	MYO7A	P78427	786
ATOH1	SHH	Q15465	750
ATOH1	MUC5AC	P98088	732
ATOH1	GFI1	Q99684	727
ATOH1	HES5	Q5TA89	706
ATOH1	LHX9	Q9NQ69	676
ATOH1	LHX2	P50458	675
ATOH1	LGR5	O75473	671
ATOH1	CTBP2	P56545	666
ATOH1	PAX2	Q02962	636

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CCL1	ATOH1	psi-mi:“MI:0915”(physical association)	0.370
	ATOH1	psi-mi:“MI:0915”(physical association)	0.370
CXCL9	ATOH1	psi-mi:“MI:0915”(physical association)	0.370
IFNA8	ATOH1	psi-mi:“MI:0915”(physical association)	0.370
IL18	ATOH1	psi-mi:“MI:0915”(physical association)	0.370
IL31	ATOH1	psi-mi:“MI:0915”(physical association)	0.370
PF4V1	ATOH1	psi-mi:“MI:0915”(physical association)	0.370
TNFSF4	ATOH1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (83): HUWE1 (Affinity Capture-Western), ATOH1 (Affinity Capture-Western), HUWE1 (Affinity Capture-MS), PRKDC (Affinity Capture-MS), MAP1B (Affinity Capture-MS), DYNC1H1 (Affinity Capture-MS), KIF11 (Affinity Capture-MS), SRRM2 (Affinity Capture-MS), MACF1 (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), HERC2 (Affinity Capture-MS), RNF213 (Affinity Capture-MS), UBR5 (Affinity Capture-MS), UTRN (Affinity Capture-MS)

ESM2 similar proteins: A1Z6W3, A1Z9P3, A8X633, B3MT31, B3P851, B4G2G5, B4IC49, B4M140, B4NFJ7, B4PRU6, E1JIT7, P08155, P10070, P10181, P17671, P18490, P22293, P27715, P29776, P91620, Q05A36, Q09103, Q0VGT2, Q17308, Q174I2, Q21227, Q23977, Q24459, Q292U2, Q292U5, Q4LBB6, Q5IS79, Q7JXG9, Q7KTX8, Q7QJT4, Q8IVW6, Q8MQW8, Q91661, Q92858, Q93560

Diamond homologs: A8E5T6, B6VQA1, O13125, O13126, O16867, O35437, O42202, O42606, O43680, O57598, O60682, O73615, O73823, O88940, O93507, O96004, O96642, P13903, P17542, P22091, P24899, P26687, P46581, P48985, P48987, P57100, P57101, P57102, P59101, P61295, P61296, P70661, P79765, P79782, P97831, P97832, Q02575, Q02576, Q02577, Q0VCE2

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ATOH1	“up-regulates quantity by expression”	HES6	“transcriptional regulation”
ATOH1	“up-regulates quantity by expression”	MUC2	“transcriptional regulation”
JAK2	“up-regulates quantity”	ATOH1	phosphorylation
HUWE1	“down-regulates quantity”	ATOH1	ubiquitination
HES1	“down-regulates quantity by repression”	ATOH1	“transcriptional regulation”
HES5	“down-regulates quantity by repression”	ATOH1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

81 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	69
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
813817	NM_005172.2(ATOH1):c.1030del (p.His344fs)	Pathogenic
3389839	NM_005172.2(ATOH1):c.901_902dup (p.Leu302fs)	Likely pathogenic
443904	GRCh37/hg19 4q22.1-22.3(chr4:89891197-98235479)x1	Likely pathogenic
4526744	NM_005172.2(ATOH1):c.1024del (p.Ser342fs)	Likely pathogenic

SpliceAI

73 predictions. Top by Δscore:

Variant	Effect	Δscore
4:93829291:TGA:T	donor_gain	0.7800
4:93829373:CAG:C	acceptor_gain	0.6100
4:93829292:GAA:G	donor_gain	0.5600
4:93829293:AAA:A	donor_gain	0.5600
4:93829874:C:CA	acceptor_gain	0.5400
4:93829374:AGCAA:A	acceptor_gain	0.5200
4:93829735:G:GT	donor_gain	0.4800
4:93829875:G:A	acceptor_gain	0.4800
4:93829775:A:T	donor_gain	0.4300
4:93829780:ACTC:A	donor_gain	0.4300
4:93829874:CGGG:C	acceptor_gain	0.4300
4:93829822:A:T	donor_gain	0.4100
4:93829372:CCA:C	acceptor_gain	0.3900
4:93829735:G:T	donor_gain	0.3900
4:93829774:G:T	donor_gain	0.3900
4:93829821:G:GT	donor_gain	0.3900
4:93829375:G:C	acceptor_gain	0.3800
4:93829663:G:GT	donor_gain	0.3800
4:93829774:G:GT	donor_gain	0.3700
4:93829497:AAC:A	acceptor_gain	0.3600
4:93829687:C:G	donor_gain	0.3600
4:93829773:G:GT	donor_gain	0.3600
4:93829993:A:T	donor_gain	0.3600
4:93828782:T:A	donor_gain	0.3500
4:93829708:G:GT	donor_gain	0.3500
4:93829054:C:T	donor_gain	0.3400
4:93829968:A:AG	acceptor_gain	0.3400
4:93829969:G:GG	acceptor_gain	0.3400
4:93829371:TCCAG:T	acceptor_gain	0.3200
4:93829497:A:AG	acceptor_gain	0.3200

AlphaMissense

2292 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:93829416:G:C	A164P	1.000
4:93829417:C:A	A164D	1.000
4:93829419:A:G	N165D	1.000
4:93829421:C:A	N165K	1.000
4:93829421:C:G	N165K	1.000
4:93829422:G:C	A166P	1.000
4:93829426:G:C	R167T	1.000
4:93829426:G:T	R167M	1.000
4:93829427:G:C	R167S	1.000
4:93829427:G:T	R167S	1.000
4:93829428:G:A	E168K	1.000
4:93829429:A:C	E168A	1.000
4:93829429:A:G	E168G	1.000
4:93829429:A:T	E168V	1.000
4:93829430:G:C	E168D	1.000
4:93829430:G:T	E168D	1.000
4:93829432:G:C	R169P	1.000
4:93829435:G:C	R170P	1.000
4:93829437:A:G	R171G	1.000
4:93829438:G:C	R171T	1.000
4:93829438:G:T	R171M	1.000
4:93829439:G:C	R171S	1.000
4:93829439:G:T	R171S	1.000
4:93829441:T:A	M172K	1.000
4:93829441:T:C	M172T	1.000
4:93829441:T:G	M172R	1.000
4:93829442:G:A	M172I	1.000
4:93829442:G:C	M172I	1.000
4:93829442:G:T	M172I	1.000
4:93829444:A:C	H173P	1.000

dbSNP variants (sampled 300 via entrez): RS1000357363 (4:93830656 C>G,T), RS10009502 (4:93828907 C>A,G), RS10015253 (4:93827138 T>A,C), RS1002334253 (4:93831062 T>G), RS1002747340 (4:93830799 T>C), RS1004166245 (4:93827395 T>A,C), RS1004237016 (4:93830750 T>A), RS1004289433 (4:93830452 T>C,G), RS1004738475 (4:93831440 G>T), RS1005171977 (4:93828438 C>A), RS1005222691 (4:93828111 G>T), RS1007462323 (4:93830345 C>T), RS1007926998 (4:93830112 T>C), RS1008132452 (4:93827553 G>A), RS1008602450 (4:93827386 G>T)

Disease associations

OMIM: gene MIM:601461 | disease phenotypes: MIM:620284, MIM:607596

GenCC curated gene-disease

Disease	Classification	Inheritance
pontocerebellar hypoplasia	Moderate	Autosomal recessive
hearing loss, autosomal dominant 89	Limited	Autosomal dominant

Mondo (2): hearing loss, autosomal dominant 89 (MONDO:0859528), pontocerebellar hypoplasia (MONDO:0020135)

Orphanet (1): Non-syndromic pontocerebellar hypoplasia (Orphanet:98523)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0003577	Congenital onset
HP:0011463	Childhood onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007856_43	Colorectal cancer or advanced adenoma	1.000000e-08
GCST009391_1077	Metabolite levels	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010529	ribose-5-phosphate measurement
EFO:0010530	ribulose-5-phosphate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580383	Pontocerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	2
arsenite	increases methylation	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Formaldehyde	increases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0F1	SEES3-1V human ATOH1, clone1	Embryonic stem cell	Male
CVCL_A0F2	SEES3-1V human ATOH1, clone2	Embryonic stem cell	Male
CVCL_A0F3	SEES3-1V human ATOH1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.