Isolated foveal hypoplasia

Summary

Isolated foveal hypoplasia (MONDO:0034978) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated foveal hypoplasia
Mondo ID	MONDO:0034978
Orphanet	519398
ICD-10-CM	H35.8
UMLS	C1850993
MedGen	376923
GARD	0022127
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › isolated foveal hypoplasia

Related subtypes (31): retinal ischemia, rubeosis iridis, retinal vascular disorder, retinitis, retinal nerve fiber layer disorder, retinal edema, retinal degeneration, night blindness, hypertensive retinopathy, macular holes, retinal detachment, iris hypoplasia with glaucoma, angioid streaks, bradyopsia, myopic macular degeneration, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, congenital retinal arteriovenous communication, Eales disease, central serous chorioretinopathy, achromatopsia, cancer-associated retinopathy, persistent placoid maculopathy, inherited vitreoretinopathy, retina neoplasm, retinal ciliopathy, melanoma associated retinopathy, acute macular neuroretinopathy, autoimmune retinopathy, proliferative vitreoretinopathy, isolated chorioretinal dystrophy, torpedo maculopathy

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4796483	NM_001080442.3(SLC38A8):c.932C>T (p.Pro311Leu)	SLC38A8	Likely pathogenic	criteria provided, single submitter
3896413	NM_001080442.3(SLC38A8):c.682G>A (p.Gly228Arg)	SLC38A8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC38A8	Orphanet:397618	Foveal hypoplasia-optic nerve decussation defect-anterior segment dysgenesis syndrome

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
SLC38A8	HGNC:32434	ENSG00000166558	A6NNN8	Solute carrier family 38 member 8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC38A8	Solute carrier family 38 member 8	Electrogenic sodium-dependent amino acid transporter with a preference for L-glutamine, L-alanine, L-histidine, L-aspartate and L-arginine.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC38A8	Other/Unknown	no		AA_transpt_TM

Expression context

Cohort genes with no expression data: 0.

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
amygdala	1
male germ line stem cell (sensu Vertebrata) in testis	1
temporal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC38A8	80	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, amygdala, temporal lobe

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC38A8	581

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC38A8	A6NNN8	83.83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
aspartate metabolic process	1	2106.5×	0.002	SLC38A8
retinal pigment epithelium development	1	1685.2×	0.002	SLC38A8
optic nerve development	1	1203.7×	0.002	SLC38A8
viral genome replication	1	1123.5×	0.002	SLC38A8
amino acid transmembrane transport	1	732.7×	0.002	SLC38A8
response to virus	1	144.0×	0.009	SLC38A8
neuron projection development	1	122.1×	0.009	SLC38A8
visual perception	1	79.5×	0.013	SLC38A8

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC38A8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	SLC38A8

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC38A8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.