Foveal hypoplasia 3

Summary

Foveal hypoplasia 3 (MONDO:0975805) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	foveal hypoplasia 3
Mondo ID	MONDO:0975805
OMIM	620958
UMLS	C5975405
MedGen	1874935
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › foveal hypoplasia › foveal hypoplasia 3

Related subtypes (3): foveal hypoplasia 1, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, GPR143-related foveal hypoplasia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3340538	NM_001621.5(AHR):c.899_908+15del	AHR	Pathogenic	no assertion criteria provided
635167	NM_001621.5(AHR):c.1861C>T (p.Gln621Ter)	AHR	Pathogenic/Likely pathogenic	no assertion criteria provided
3383354	NM_001621.5(AHR):c.528G>A (p.Trp176Ter)	AHR	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
AHR	Moderate	Autosomal recessive	foveal hypoplasia 3	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AHR	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AHR	HGNC:348	ENSG00000106546	P35869	Aryl hydrocarbon receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AHR	Aryl hydrocarbon receptor	Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and canc…

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AHR	Transcription factor	no		PAS, PAC, bHLH_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
parietal pleura	1
pleura	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AHR	275	ubiquitous	marker	visceral pleura, parietal pleura, pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AHR	979

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AHR	P35869	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Aryl hydrocarbon receptor signalling	1	1903.3×	0.005	AHR
Cytochrome P450 - arranged by substrate type	1	713.8×	0.006	AHR
Xenobiotics	1	496.5×	0.006	AHR
Endogenous sterols	1	393.8×	0.006	AHR
Phase I - Functionalization of compounds	1	219.6×	0.009	AHR
Regulation of lipid metabolism by PPARalpha	1	141.0×	0.011	AHR
Biological oxidations	1	129.8×	0.011	AHR
PPARA activates gene expression	1	94.4×	0.013	AHR
Metabolism of lipids	1	31.6×	0.035	AHR
Metabolism	1	11.6×	0.086	AHR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to 2,3,7,8-tetrachlorodibenzodioxine	1	5617.3×	0.002	AHR
regulation of B cell proliferation	1	4213.0×	0.002	AHR
negative regulation of T cell mediated immune response to tumor cell	1	2106.5×	0.002	AHR
cellular response to molecule of bacterial origin	1	2106.5×	0.002	AHR
regulation of adaptive immune response	1	1872.4×	0.002	AHR
cellular response to forskolin	1	1123.5×	0.003	AHR
blood vessel development	1	374.5×	0.008	AHR
cellular response to cAMP	1	290.6×	0.009	AHR
circadian regulation of gene expression	1	234.1×	0.009	AHR
response to toxic substance	1	210.7×	0.009	AHR
xenobiotic metabolic process	1	149.1×	0.012	AHR
negative regulation of inflammatory response	1	137.0×	0.012	AHR
regulation of gene expression	1	83.4×	0.018	AHR
response to xenobiotic stimulus	1	69.1×	0.021	AHR
regulation of DNA-templated transcription	1	31.6×	0.040	AHR
negative regulation of DNA-templated transcription	1	31.6×	0.040	AHR
apoptotic process	1	28.7×	0.040	AHR
positive regulation of DNA-templated transcription	1	27.9×	0.040	AHR
positive regulation of transcription by RNA polymerase II	1	14.9×	0.071	AHR
regulation of transcription by RNA polymerase II	1	11.7×	0.086	AHR

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
AHR	TAPINAROF

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AHR	9	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TAPINAROF	4	AHR
ARUNDINE	3	AHR
INDIGO	3	AHR
INDIRUBIN	2	AHR
EZUTROMID	2	AHR
ILANTIMOD	2	AHR
KAEMPFEROL	1	AHR
TRANSTORINE	1	AHR
L-KYNURENINE	1	AHR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AHR	293	Binding:225, ADMET:58, Functional:7, Toxicity:3

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
AHR	293

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

9 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
TAPINAROF	4	AHR
ARUNDINE	3	AHR
INDIGO	3	AHR
INDIRUBIN	2	AHR
EZUTROMID	2	AHR
ILANTIMOD	2	AHR
KAEMPFEROL	1	AHR
TRANSTORINE	1	AHR
L-KYNURENINE	1	AHR

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	AHR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.