ATOH7

Summary

ATOH7 (atonal bHLH transcription factor 7, HGNC:13907) is a protein-coding gene on chromosome 10q21.3, encoding Transcription factor ATOH7 (Q8N100). Transcription factor that binds to DNA at the consensus sequence 5’-CAG[GC]TG-3'.

This intronless gene encodes a member of the basic helix-loop-helix family of transcription factors, with similarity to Drosophila atonal gene that controls photoreceptor development. Studies in mice suggest that this gene plays a central role in retinal ganglion cell and optic nerve formation. Mutations in this gene are associated with nonsyndromic congenital retinal nonattachment.

Source: NCBI Gene 220202 — RefSeq curated summary.

At a glance

• Gene–disease (curated): persistent hyperplastic primary vitreous, autosomal recessive (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 28
• Clinical variants (ClinVar): 142 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 35
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_145178

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13907
Approved symbol	ATOH7
Name	atonal bHLH transcription factor 7
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	Math5, bHLHa13
Ensembl gene	ENSG00000179774
Ensembl biotype	protein_coding
OMIM	609875
Entrez	220202

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000373673

RefSeq mRNA: 1 — MANE Select: NM_145178 NM_145178

CCDS: CCDS7276

Canonical transcript exons

ENST00000373673 — 1 exons

Exon	Start	End
ENSE00001461199	68230595	68232113

Expression profiles

Bgee: expression breadth ubiquitous, 104 present calls, max score 79.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4217 / max 96.3866, expressed in 116 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109743	0.2884	82
109742	0.1333	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.11	gold quality
prefrontal cortex	UBERON:0000451	70.86	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.01	gold quality
middle temporal gyrus	UBERON:0002771	67.00	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	66.80	gold quality
anterior cingulate cortex	UBERON:0009835	66.80	gold quality
right lobe of liver	UBERON:0001114	66.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	66.41	silver quality
frontal cortex	UBERON:0001870	65.91	gold quality
neocortex	UBERON:0001950	65.38	gold quality
right frontal lobe	UBERON:0002810	64.90	gold quality
cerebellar cortex	UBERON:0002129	64.20	gold quality
cerebellar hemisphere	UBERON:0002245	64.13	gold quality
cerebral cortex	UBERON:0000956	63.76	gold quality
amygdala	UBERON:0001876	63.54	gold quality
cerebellum	UBERON:0002037	63.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.96	gold quality
primary visual cortex	UBERON:0002436	60.97	gold quality
temporal lobe	UBERON:0001871	60.30	gold quality
Ammon’s horn	UBERON:0001954	59.94	gold quality
endothelial cell	CL:0000115	59.68	gold quality
cortical plate	UBERON:0005343	59.47	gold quality
nucleus accumbens	UBERON:0001882	59.09	gold quality
superior frontal gyrus	UBERON:0002661	58.94	gold quality
forebrain	UBERON:0001890	58.26	gold quality
brain	UBERON:0000955	57.90	gold quality
caudate nucleus	UBERON:0001873	56.47	gold quality
occipital lobe	UBERON:0002021	56.07	gold quality
entorhinal cortex	UBERON:0002728	55.61	silver quality
putamen	UBERON:0001874	54.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	2608.40
E-ANND-3	no	1.30

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
ATOH7
BHLHE22	Unknown
GABRB3
GFI1	Activation
ISL1	Activation
ISL2	Activation
NEUROD1	Unknown
NEUROG2	Repression
NHLH1	Activation
NHLH2	Activation
POU4F2	Activation
PRPH2

JASPAR motifs

Motif	Name	Family
MA1468.1	ATOH7	Tal-related

JASPAR matrix evidence (PMIDs): PMID:23293286

Upstream regulators (CollecTRI, top): ATOH1, ATOH7, ISL1, MSX2, NEUROG2, PAX6, PTF1A

miRNA regulators (miRDB)

36 targeting ATOH7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-6783-5P	97.67	67.21	1528

Literature-anchored findings (GeneRIF, showing 23)

• Genome-wide association identifies ATOH7 as a major gene determining human optic disc size (PMID:20395239)
• Polymorphisms of ATOH7, TGFBR3 and CARD10 influence the size of optic disc area. (PMID:21307088)
• ATOH7 is significantly associated with open-angle glaucoma. (PMID:21427129)
• This study demonistrated that Deletion of a remote enhancer near ATOH7 disrupts retinal neurogenesis, causing NCRNA disease. (PMID:21441919)
• Report Math5 expression/function in retinal ganglion cells. (PMID:22019371)
• findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye; study provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression (PMID:22068589)
• combination of ATOH7 and RFTN1 SNPs increased risk to POAG, indicating their diversified effects in the complex genetics of glaucoma. (PMID:22222511)
• a bHLH mutation in ATOH7 causes recessive persistent hyperplasia of the primary vitreous (PMID:22645276)
• Mutations within the ATOH7 gene are not implicated in the pathogenesis of optic nerve hypoplasia in our patient cohort. (PMID:23802135)
• This study finds that ATOH7 is associated with optic disc size but not independently with cup/disk ratio. (PMID:24457358)
• The significant association of three common variants in TMCO1, ATOH7, and CAV1 with primary open angle, primary angle closure, and pseudoexfoliation glaucoma was found in Pakistani cohorts. (PMID:25489222)
• Single nucleotide polymorphism in ATOH7 gene is associated with primary open angle glaucoma. (PMID:25798827)
• Familial linkage studies for primary angle-closure glaucoma have been performed and identified ATOH7 causative primary angle-closure glaucoma disease (PMID:26497787)
• In conclusion, we have identified a homozygous mutation in the ATOH7 gene in a patient with nonsyndromic congenital retinal nonattachment. (PMID:26933893)
• The genotype and allele frequencies of the polymorphism in ATOH7 did not show any statistically significant association with primary open angle glaucomacompared to controls. (PMID:27617586)
• We discovered a novel SNP, rs56238729 (P = 1.22 x 10-13), in the ATOH7-PBLD region that is significantly associated with VCDR in Latino individuals. (PMID:28061514)
• We evaluated 21 consanguineous NCRNA pedigrees and identified the causal mutations in known retinal genes in 13 out of our 21 families. We found mutations in ATOH7 in three families. (PMID:28192794)
• These results demonstrate the high potency of human ATOH7 in promoting early retinogenesis and specifying the retinal ganglion cells differentiation program, thus providing insight for manipulating retinal ganglion cells production from stem cell-derived retinal organoids. (PMID:29717171)
• Our present results showed that the T allele of ATOH7 conferred an independent risk of non-arteritic ischemic optic neuropathy. (PMID:29792847)
• Atonal homolog 7 (ATOH7) loss-of-function mutations in predominant bilateral optic nerve hypoplasia. (PMID:31696227)
• Functional Characterization of an In-Frame Deletion in the Basic Domain of the Retinal Transcription Factor ATOH7. (PMID:35162975)
• OCULAR FEATURES ASSOCIATED WITH MUTATIONS IN ATOH7 GENE OVERLAP THOSE WITH FAMILIAL EXUDATIVE VITREORETINOPATHY. (PMID:35389970)
• Whole exome sequencing revealed novel pathogenic variants in Vietnamese patients with FEVR. (PMID:37089697)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	atoh7	ENSDARG00000069552
mus_musculus	Atoh7	ENSMUSG00000036816
rattus_norvegicus	Atoh7	ENSRNOG00000078656
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), ATOH1 (ENSG00000172238), OLIG3 (ENSG00000177468), NEUROG2 (ENSG00000178403), BHLHA15 (ENSG00000180535), BHLHE22 (ENSG00000180828), NEUROG1 (ENSG00000181965), OLIG1 (ENSG00000184221), OLIG2 (ENSG00000205927)

Protein

Protein identifiers

Transcription factor ATOH7 — Q8N100 (reviewed: Q8N100)

Alternative names: Atonal bHLH transcription factor 7, Class A basic helix-loop-helix protein 13, Protein atonal homolog 7

All UniProt accessions (2): Q8N100, F1T0H4

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds to DNA at the consensus sequence 5’-CAG[GC]TG-3’. Dimerization with TCF3 isoform E47 may be required in certain situations. Binds to gene promoters and enhancer elements, and thereby regulates a transcriptional program of retinal ganglion cell (RGC) determinant genes. Although the exact mechanism is not certain, retinal transcription regulation by ATOH7 has a role in RGC determination and survival, photoreceptor population development, targeting of RGC axons to the optic nerve and development of the retino-hypothalamic tract. Binds to its own promoter and enhancer sequences, suggesting autoregulation of ATOH7 transcription. Required for retinal circadian rhythm photoentrainment. Plays a role in brainstem auditory signaling and binaural processing.

Subunit / interactions. Forms a heterodimer with TCF3 isoform E47; interaction may be required for DNA-binding in certain situations.

Subcellular location. Nucleus. Perikaryon. Cell projection. Axon.

Disease relevance. Persistent hyperplastic primary vitreous, autosomal recessive (PHPVAR) [MIM:221900] A developmental eye malformation associated with microphthalmia, cataract, glaucoma, and congenital retinal non-attachment. It is due to failure of the primary vitreous to regress in utero, resulting in the presence of a retrolental fibrovascular membrane with persistence of the posterior portion of the tunica vasculosa lentis and hyaloid artery. Disease manifestations range from a trivial remnant of hyaloid vessels to a dense fibrovascular mass causing lens opacity and retinal detachment. The disease is caused by variants affecting the gene represented in this entry. A 6.5 kb deletion that spans a remote cis regulatory element 20 kb upstream from ATOH7 has been found in PHPVAR patients.

RefSeq proteins (1): NP_660161* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR032663	ATOH7_bHLH	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050359	bHLH_transcription_factors	Family

Pfam: PF00010

UniProt features (13 total): sequence variant 9, mutagenesis site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N100-F1	72.79	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
56	loss of dna-binding activity; loss of ability to restore retinal ganglion cell development in retinal explants from a mo
59	abolishes heterodimerization with tcf3 isoform e47; no effect on nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): GOBP_CIRCADIAN_RHYTHM, RNGTGGGC_UNKNOWN, GOBP_PHOTOPERIODISM, GOBP_RETINAL_GANGLION_CELL_AXON_GUIDANCE, GOBP_NEUROGENESIS, chr10q21, GOBP_REGULATION_OF_AXON_GUIDANCE, TAL1ALPHAE47_01, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_CRANIAL_NERVE_DEVELOPMENT, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_TAXIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, MYOD_01, OCT1_03

GO Biological Process (16): neural retina development (GO:0003407), regulation of transcription by RNA polymerase II (GO:0006357), sensory organ development (GO:0007423), circadian rhythm (GO:0007623), response to auditory stimulus (GO:0010996), optic nerve development (GO:0021554), entrainment of circadian clock by photoperiod (GO:0043153), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron fate commitment (GO:0048663), axon development (GO:0061564), positive regulation of retinal ganglion cell axon guidance (GO:1902336), regulation of DNA-templated transcription (GO:0006355), nervous system development (GO:0007399), entrainment of circadian clock (GO:0009649), cell differentiation (GO:0030154), system development (GO:0048731)

GO Molecular Function (7): transcription cis-regulatory region binding (GO:0000976), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), protein dimerization activity (GO:0046983), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), centriole (GO:0005814), cytosol (GO:0005829), axon (GO:0030424), perikaryon (GO:0043204), sperm midpiece (GO:0097225), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
anatomical structure development	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
retina development in camera-type eye	1
regulation of DNA-templated transcription	1
animal organ development	1
rhythmic process	1
response to mechanical stimulus	1
cranial nerve development	1
photoperiodism	1
entrainment of circadian clock	1
positive regulation of DNA-templated transcription	1
neuron differentiation	1
cell fate commitment	1
neuron projection development	1
retinal ganglion cell axon guidance	1
regulation of retinal ganglion cell axon guidance	1
positive regulation of axon guidance	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
system development	1
response to external stimulus	1
regulation of circadian rhythm	1
cellular developmental process	1
multicellular organism development	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
protein binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATOH7	GDF11	O95390	904
ATOH7	POU4F2	Q12837	837
ATOH7	VSX2	P58304	800
ATOH7	VSX1	Q9NZR4	737
ATOH7	PAX6	P26367	687
ATOH7	CRX	O43186	680
ATOH7	SIX6	O95475	670
ATOH7	FOXN4	Q96NZ1	665
ATOH7	ISL1	P20663	650
ATOH7	POU4F1	Q01851	647
ATOH7	SIX3	O95343	613
ATOH7	TMCO1	Q9UM00	606
ATOH7	POU4F3	Q15319	586
ATOH7	GDF9	O60383	584
ATOH7	OTX2	P32243	580

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TCF4	ATOH7	psi-mi:“MI:0915”(physical association)	0.560
TCF3	ATOH7	psi-mi:“MI:0915”(physical association)	0.400
ATOH7	TCF4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): TCF4 (Two-hybrid)

ESM2 similar proteins: A8E5T6, O13125, O13126, O35437, O43680, O57598, O60682, O73615, O88940, P12979, P13903, P15173, P15375, P19335, P23409, P34060, P41133, P41138, P49812, P59101, P70562, P70661, P79782, P97831, Q01795, Q02535, Q02576, Q02577, Q16559, Q20561, Q32PV5, Q3YFL6, Q5E981, Q5E9S3, Q62282, Q6GNB7, Q6VNZ9, Q712G9, Q7YS80, Q8AW52

Diamond homologs: A3KNX5, O13125, O13126, O57598, P48985, P48987, P70661, Q10574, Q4ZHW1, Q5RJB0, Q7RTS1, Q7RTU4, Q7ZSX3, Q8AW52, Q8N100, Q923Z4, Q96RJ6, Q9QX98, Q9VGJ5, A8E5T6, B6VQA1, O16867, O35437, O42202, O42606, O43680, O60682, O73615, O73823, O88940, O93507, O96004, O96642, P13903, P17542, P22091, P24899, P26687, P46581, P57100

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATOH7	“up-regulates quantity by expression”	POU4F2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	108
Likely benign	21
Benign	7

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
144065	NM_145178.4(ATOH7):c.146A>T (p.Glu49Val)	Pathogenic
144067	NM_145178.4(ATOH7):c.136A>C (p.Asn46His)	Pathogenic
30807	NC_000010.11:g.68247368_68253890del	Pathogenic
812672	NM_145178.4(ATOH7):c.175G>A (p.Ala59Thr)	Pathogenic
2504092	NM_145178.4(ATOH7):c.154C>G (p.Arg52Gly)	Likely pathogenic

SpliceAI

174 predictions. Top by Δscore:

Variant	Effect	Δscore
10:68231479:CCACC:C	acceptor_gain	0.6500
10:68231480:CACCC:C	acceptor_gain	0.6500
10:68231482:CC:C	acceptor_gain	0.6400
10:68231483:CC:C	acceptor_gain	0.6400
10:68231940:A:C	donor_gain	0.6400
10:68231285:G:A	donor_gain	0.5000
10:68231484:C:CC	acceptor_gain	0.5000
10:68231479:C:CT	donor_gain	0.4800
10:68231480:CACC:C	acceptor_gain	0.4600
10:68231446:TGG:T	donor_gain	0.4500
10:68231443:A:AC	donor_gain	0.4200
10:68231444:C:CC	donor_gain	0.4200
10:68231304:G:T	acceptor_gain	0.4100
10:68231487:C:CT	acceptor_gain	0.4100
10:68231597:G:A	donor_gain	0.4100
10:68231480:C:CT	donor_gain	0.4000
10:68231481:ACCC:A	acceptor_loss	0.4000
10:68231482:CCCT:C	acceptor_loss	0.4000
10:68231483:CCTGC:C	acceptor_loss	0.4000
10:68231484:C:A	acceptor_loss	0.4000
10:68231485:T:C	acceptor_loss	0.4000
10:68231486:G:C	acceptor_loss	0.4000
10:68231807:CGTG:C	donor_gain	0.4000
10:68231482:C:A	donor_gain	0.3900
10:68231964:A:T	donor_gain	0.3900
10:68231969:T:TA	donor_gain	0.3900
10:68231352:A:AC	donor_gain	0.3800
10:68231353:C:CC	donor_gain	0.3800
10:68231724:CAGG:C	donor_gain	0.3800
10:68231725:AGGA:A	donor_gain	0.3800

AlphaMissense

978 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:68231433:A:G	L82P	1.000
10:68231444:C:A	K78N	1.000
10:68231444:C:G	K78N	1.000
10:68231446:T:C	K78E	1.000
10:68231490:A:G	L63S	1.000
10:68231403:A:G	L92P	0.999
10:68231421:A:G	L86P	0.999
10:68231433:A:T	L82Q	0.999
10:68231445:T:A	K78M	0.999
10:68231446:T:G	K78Q	0.999
10:68231448:G:A	S77F	0.999
10:68231448:G:T	S77Y	0.999
10:68231475:G:T	P68H	0.999
10:68231476:G:A	P68S	0.999
10:68231478:A:T	V67D	0.999
10:68231488:G:T	R64S	0.999
10:68231498:G:C	F60L	0.999
10:68231498:G:T	F60L	0.999
10:68231499:A:C	F60C	0.999
10:68231499:A:G	F60S	0.999
10:68231500:A:G	F60L	0.999
10:68231507:G:C	N57K	0.999
10:68231507:G:T	N57K	0.999
10:68231511:A:G	L56P	0.999
10:68231511:A:T	L56H	0.999
10:68231519:C:A	M53I	0.999
10:68231519:C:G	M53I	0.999
10:68231519:C:T	M53I	0.999
10:68231520:A:T	M53K	0.999
10:68231524:G:T	R52S	0.999

dbSNP variants (sampled 300 via entrez): RS1000387123 (10:68230462 G>C), RS1000672960 (10:68231665 T>C), RS1000974469 (10:68232128 G>A), RS1001110908 (10:68231922 G>A), RS1002080116 (10:68232750 T>A,C), RS1002134292 (10:68233112 C>A), RS1005617966 (10:68232593 TTAAG>T), RS1005769635 (10:68231033 G>T), RS1005821943 (10:68231326 G>A,C), RS1007609765 (10:68230151 T>C), RS1008285382 (10:68233592 T>C), RS1009055101 (10:68230884 G>A,T), RS1009595438 (10:68230474 A>G), RS1013282931 (10:68232723 A>C), RS1013711090 (10:68231630 T>A,C,G)

Disease associations

OMIM: gene MIM:609875 | disease phenotypes: MIM:221900, MIM:136520

GenCC curated gene-disease

Disease	Classification	Inheritance
persistent hyperplastic primary vitreous, autosomal recessive	Strong	Autosomal recessive
anterior segment dysgenesis 7	Supportive	Autosomal recessive
persistent hyperplastic primary vitreous	Supportive	Autosomal dominant

Mondo (4): persistent hyperplastic primary vitreous, autosomal recessive (MONDO:0009097), foveal hypoplasia (MONDO:0044203), anterior segment dysgenesis 7 (MONDO:0010015), persistent hyperplastic primary vitreous (MONDO:0019631)

Orphanet (2): Persistent hyperplastic primary vitreous (Orphanet:91495), OBSOLETE: Congenital blindness due to retinal non-attachment (Orphanet:300337)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000554	Uveitis
HP:0000555	Leukocoria
HP:0000557	Buphthalmos
HP:0000565	Esotropia
HP:0000568	Microphthalmia
HP:0000594	Shallow anterior chamber
HP:0000612	Iris coloboma
HP:0000618	Blindness
HP:0000646	Amblyopia
HP:0000667	Phthisis bulbi
HP:0001104	Macular hypoplasia
HP:0003577	Congenital onset
HP:0007663	Reduced visual acuity
HP:0007899	Retinal nonattachment
HP:0007917	Tractional retinal detachment
HP:0007957	Corneal opacity
HP:0007968	Remnants of the hyaloid vascular system
HP:0008052	Retinal fold
HP:0009917	Persistent pupillary membrane
HP:0009926	Epiphora
HP:0010766	Ectopic calcification
HP:0011484	Posterior synechiae of the anterior chamber
HP:0011885	Hemorrhage of the eye
HP:0011886	Hyphema

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000657_1	Optic nerve measurement (disc area)	3.000000e-10
GCST000659_4	Optic nerve measurement (cup area)	2.000000e-07
GCST000699_2	Optic disc parameters	3.000000e-35
GCST000700_8	Vertical cup-disc ratio	2.000000e-08
GCST000970_1	Optic disc area	2.000000e-15
GCST001959_6	Eating disorders (purging via substances)	4.000000e-06
GCST002626_6	Vertical cup-disc ratio	5.000000e-31
GCST002762_12	Optic cup area	8.000000e-08
GCST002762_27	Optic cup area	4.000000e-10
GCST002765_4	Optic disc area	1.000000e-73
GCST002765_9	Optic disc area	2.000000e-63
GCST004047_2	Optic nerve measurement (cup-to-disc ratio)	1.000000e-13
GCST004075_20	Vertical cup-disc ratio	2.000000e-42
GCST004075_21	Vertical cup-disc ratio	7.000000e-46
GCST004076_20	Optic disc area	2.000000e-112
GCST004076_6	Optic disc area	2.000000e-90
GCST004137_19	Optic cup area	5.000000e-12
GCST004137_35	Optic cup area	2.000000e-09
GCST008163_13	Height	4.000000e-06
GCST009391_1222	Metabolite levels	5.000000e-06
GCST009404_19	Optic cup area	9.000000e-13
GCST009411_18	Optic disc area	4.000000e-89
GCST009412_5	Vertical cup-disc ratio	3.000000e-44
GCST009427_1	Optic disc radius	2.000000e-10
GCST009462_104	Optic disc size	3.000000e-246
GCST009723_43	Vertical cup-disc ratio (adjusted for vertical disc diameter)	7.000000e-35
GCST009724_21	Vertical cup-disc ratio (multi-trait analysis)	3.000000e-67
GCST90020028_48	Hip circumference adjusted for BMI	5.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006939	cup-to-disc ratio measurement
EFO:0010421	triacylglycerol 54:3 measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D054514	Persistent Hyperplastic Primary Vitreous	C11.250.616; C16.131.384.725
C566966	Persistent Hyperplastic Primary Vitreous, Autosomal Recessive (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
Valproic Acid	decreases expression, affects cotreatment	4
Vorinostat	affects cotreatment, increases expression	2
trichostatin A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Smoke	decreases expression	1
Triclosan	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_A0F4	SEES3-1V human ATOH7, clone1	Embryonic stem cell	Male
CVCL_A0F5	SEES3-1V human ATOH7, clone2	Embryonic stem cell	Male
CVCL_A0F6	SEES3-1V human ATOH7, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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