Cone-rod dystrophy 10

Summary

Cone-rod dystrophy 10 (MONDO:0012464) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 88

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 10
Mondo ID	MONDO:0012464
MeSH	C564597
OMIM	610283
DOID	DOID:0111017
UMLS	C1846529
MedGen	337598
GARD	0015477
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 10 · cone-rod dystrophy caused by mutation in SEMA4A · cone-rod dystrophy type 10 · CORD10 · SEMA4A cone-rod dystrophy

Data availability: 88 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › cone-rod dystrophy › cone-rod dystrophy 10

Related subtypes (27): cone-rod dystrophy 2, macular degeneration, X-linked atrophic, cone-rod dystrophy 1, cone-rod dystrophy 5, cone-rod dystrophy 6, cone dystrophy 3, cone-rod dystrophy 7, cone-rod dystrophy 3, Leber congenital amaurosis 4, cone-rod dystrophy 8, Newfoundland cone-rod dystrophy, cone-rod dystrophy 13, cone-rod dystrophy 11, retinal cone dystrophy 4, cone-rod dystrophy 12, cone-rod dystrophy 9, cone-rod dystrophy 15, cone-rod dystrophy 16, cone-rod dystrophy 17, cone-rod dystrophy 18, cone-rod dystrophy 19, cone-rod dystrophy 20, cone-rod dystrophy 21, X-linked cone-rod dystrophy, cone-rod dystrophy 22, cone-rod dystrophy 14, cone-rod dystrophy 24

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

88 retrieved; paginated sample, class counts are floors:

51 uncertain significance, 24 conflicting classifications of pathogenicity, 9 benign/likely benign, 2 likely benign, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3361	NM_022367.4(SEMA4A):c.1049T>G (p.Phe350Cys)	SEMA4A	Pathogenic	no assertion criteria provided
195371	NM_022367.4(SEMA4A):c.84G>A (p.Thr28=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292843	NM_022367.4(SEMA4A):c.90C>T (p.Thr30=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292844	NM_022367.4(SEMA4A):c.95G>T (p.Gly32Val)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292845	NM_022367.4(SEMA4A):c.405T>C (p.Asn135=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292846	NM_022367.4(SEMA4A):c.492C>T (p.Ile164=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292848	NM_022367.4(SEMA4A):c.810+7G>A	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292849	NM_022367.4(SEMA4A):c.1086A>C (p.Ser362=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292851	NM_022367.4(SEMA4A):c.1215G>T (p.Thr405=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292853	NM_022367.4(SEMA4A):c.1694-13C>G	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292854	NM_022367.4(SEMA4A):c.2106C>T (p.Leu702=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292864	NM_022367.4(SEMA4A):c.*188G>T	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
292865	NM_022367.4(SEMA4A):c.*366G>A	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
727396	NM_022367.4(SEMA4A):c.1653C>A (p.Pro551=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
728541	NM_022367.4(SEMA4A):c.861G>T (p.Leu287=)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
746667	NM_022367.4(SEMA4A):c.2249A>T (p.Asp750Val)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
767708	NM_022367.4(SEMA4A):c.20G>A (p.Gly7Asp)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
767709	NM_022367.4(SEMA4A):c.1682G>A (p.Arg561His)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
806246	NM_022367.4(SEMA4A):c.302T>C (p.Ile101Thr)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
874568	NM_022367.4(SEMA4A):c.1646G>A (p.Ser549Asn)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
875440	NM_022367.4(SEMA4A):c.712C>T (p.Pro238Ser)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
875548	NM_022367.4(SEMA4A):c.*102C>G	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876464	NM_022367.4(SEMA4A):c.994G>A (p.Gly332Arg)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876549	NM_022367.4(SEMA4A):c.*334C>T	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
96033	NM_022367.4(SEMA4A):c.1301T>C (p.Met434Thr)	SEMA4A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000955	NM_022367.4(SEMA4A):c.86C>T (p.Thr29Met)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014809	NM_022367.4(SEMA4A):c.937G>A (p.Asp313Asn)	SEMA4A	Uncertain significance	criteria provided, single submitter
1022883	NM_022367.4(SEMA4A):c.473A>G (p.Asp158Gly)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1054646	NM_022367.4(SEMA4A):c.1685C>T (p.Pro562Leu)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1409212	NM_022367.4(SEMA4A):c.1991C>T (p.Pro664Leu)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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
SEMA4A	Moderate	Autosomal recessive	inherited retinal dystrophy	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SEMA4A	Orphanet:1872	Cone rod dystrophy
SEMA4A	Orphanet:440437	Familial colorectal cancer Type X
SEMA4A	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
SEMA4A	HGNC:10729	ENSG00000196189	Q9H3S1	Semaphorin-4A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SEMA4A	Semaphorin-4A	Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SEMA4A	Scaffold/PPI	no		Semap_dom, Plexin_repeat, WD40/YVTN_repeat-like_dom_sf

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SEMA4A	219	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SEMA4A	997

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SEMA4A	Q9H3S1	85.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Other semaphorin interactions	1	601.0×	0.006	SEMA4A
Semaphorin interactions	1	393.8×	0.006	SEMA4A
Axon guidance	1	45.1×	0.029	SEMA4A
Nervous system development	1	42.9×	0.029	SEMA4A
Developmental Biology	1	14.5×	0.069	SEMA4A

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
positive regulation of excitatory synapse assembly	1	5617.3×	0.001	SEMA4A
positive regulation of inhibitory synapse assembly	1	5617.3×	0.001	SEMA4A
regulation of endothelial cell migration	1	2106.5×	0.002	SEMA4A
T-helper 1 cell differentiation	1	1532.0×	0.002	SEMA4A
negative chemotaxis	1	648.1×	0.004	SEMA4A
semaphorin-plexin signaling pathway	1	401.2×	0.005	SEMA4A
neural crest cell migration	1	337.0×	0.005	SEMA4A
negative regulation of angiogenesis	1	168.5×	0.009	SEMA4A
regulation of cell shape	1	123.0×	0.011	SEMA4A
axon guidance	1	90.6×	0.013	SEMA4A
angiogenesis	1	62.4×	0.016	SEMA4A
positive regulation of cell migration	1	61.7×	0.016	SEMA4A

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
SEMA4A	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	SEMA4A

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)
SEMA4A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.