Macular dystrophy with or without cone dysfunction

Summary

Macular dystrophy with or without cone dysfunction (MONDO:0958326) is a disease caused by SAMD7 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: SAMD7 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	macular dystrophy with or without cone dysfunction
Mondo ID	MONDO:0958326
OMIM	620762
UMLS	C5935594
MedGen	1853300
GARD	0027008
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › hereditary macular dystrophy › macular dystrophy with or without cone dysfunction

Related subtypes (16): vitelliform macular dystrophy, cone dystrophy, coloboma of macula, coloboma of macula-brachydactyly type B syndrome, benign concentric annular macular dystrophy, macular dystrophy, fenestrated sheen type, macular coloboma-cleft palate-hallux valgus syndrome, macular corneal dystrophy, EEM syndrome, renal hypomagnesemia 5 with ocular involvement, macular dystrophy, X-linked, AICA-ribosiduria, occult macular dystrophy, familial flecked retinopathy, patterned dystrophy of the retinal pigment epithelium, macular dystrophy, retinal

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:

2 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3062151	NM_001304366.2(SAMD7):c.211+1G>A	SAMD7	Pathogenic	no assertion criteria provided
3062152	NM_001304366.2(SAMD7):c.1153G>A (p.Val385Ile)	SAMD7	Pathogenic	no assertion criteria provided
767105	NM_152443.3(RDH12):c.806C>G (p.Ala269Gly)	RDH12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 2 · 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
SAMD7	Strong	Autosomal recessive	macular dystrophy with or without cone dysfunction	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RDH12	Orphanet:65	Leber congenital amaurosis
RDH12	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SAMD7	HGNC:25394	ENSG00000187033	Q7Z3H4	Sterile alpha motif domain-containing protein 7	gencc,clinvar
RDH12	HGNC:19977	ENSG00000139988	Q96NR8	Retinol dehydrogenase 12	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SAMD7	Sterile alpha motif domain-containing protein 7	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, essential for establishing rod photoreceptor cell identity and function by silencing nonrod gene expression in developing rod photoreceptor cells.
RDH12	Retinol dehydrogenase 12	Retinoids dehydrogenase/reductase with a clear preference for NADP.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SAMD7	Other/Unknown	no		SAM, SAM/pointed_sf, PcG_chromatin_remod_factors
RDH12	Enzyme (other)	yes	1.1.1.105	SDR_fam, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
lymph node	1
sural nerve	1
mammalian vulva	1
skin of leg	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SAMD7	3	tissue_specific	marker	sural nerve, lymph node, cortical plate
RDH12	180	tissue_specific	marker	upper arm skin, skin of leg, mammalian vulva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RDH12	3,526
SAMD7	403

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RDH12	Q96NR8	92.21
SAMD7	Q7Z3H4	56.48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 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
Defective visual phototransduction due to RDH12 loss of function	1	11420.0×	2e-04	RDH12
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.002	RDH12

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular detoxification of aldehyde	1	1053.2×	0.005	RDH12
retinal rod cell development	1	842.6×	0.005	SAMD7
retinoid metabolic process	1	247.8×	0.007	RDH12
retinol metabolic process	1	247.8×	0.007	RDH12
negative regulation of gene expression, epigenetic	1	200.6×	0.007	SAMD7
photoreceptor cell maintenance	1	179.3×	0.007	RDH12
visual perception	1	39.8×	0.029	RDH12
negative regulation of DNA-templated transcription	1	15.8×	0.062	SAMD7

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
SAMD7	0	0
RDH12	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RDH12	1.1.1.105, 1.1.1.300	all-trans-retinol dehydrogenase (NAD+), NADP-retinol dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	RDH12
E	Difficult family or no structure, no drug	1	SAMD7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SAMD7	0	—
RDH12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.