Retinitis pigmentosa 35

Summary

Retinitis pigmentosa 35 (MONDO:0012463) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 46

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 35
Mondo ID	MONDO:0012463
MeSH	C565206
OMIM	610282
DOID	DOID:0110357
UMLS	C1853214
MedGen	339931
GARD	0010402
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 35 · retinitis pigmentosa caused by mutation in SEMA4A · retinitis pigmentosa type 35 · RP 35 · RP35 · SEMA4A retinitis pigmentosa

Data availability: 46 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 › retinitis pigmentosa › retinitis pigmentosa 35

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

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

46 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 7 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
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
1417181	NM_022367.4(SEMA4A):c.394G>A (p.Val132Ile)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1447017	NM_022367.4(SEMA4A):c.247G>C (p.Ala83Pro)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1467182	NM_022367.4(SEMA4A):c.1669C>T (p.Arg557Trp)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1503420	NM_022367.4(SEMA4A):c.1028T>C (p.Leu343Pro)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1510361	NM_022367.4(SEMA4A):c.1783C>T (p.Pro595Ser)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
167672	NM_022367.4(SEMA4A):c.1123C>T (p.Arg375Trp)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
167673	NM_022367.4(SEMA4A):c.1196A>T (p.Asp399Val)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1879096	NM_022367.4(SEMA4A):c.332G>A (p.Ser111Asn)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2151300	NM_022367.4(SEMA4A):c.94G>T (p.Gly32Trp)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442000	NM_022367.4(SEMA4A):c.807C>A (p.Cys269Ter)	SEMA4A	Uncertain significance	criteria provided, single submitter
2500821	NM_022367.4(SEMA4A):c.1064_1065del (p.Lys355fs)	SEMA4A	Uncertain significance	criteria provided, single submitter
292847	NM_022367.4(SEMA4A):c.494C>T (p.Ser165Leu)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
292850	NM_022367.4(SEMA4A):c.1094C>T (p.Thr365Ile)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
292852	NM_022367.4(SEMA4A):c.1337C>T (p.Ala446Val)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
292856	NM_022367.4(SEMA4A):c.2167C>A (p.Arg723Ser)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
292859	NM_022367.4(SEMA4A):c.2251G>A (p.Ala751Thr)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
3360	NM_022367.4(SEMA4A):c.1033G>C (p.Asp345His)	SEMA4A	Uncertain significance	criteria provided, single submitter
3892382	NM_022367.4(SEMA4A):c.2273C>G (p.Thr758Ser)	SEMA4A	Uncertain significance	criteria provided, single submitter
3892383	NM_022367.4(SEMA4A):c.913C>T (p.Arg305Cys)	SEMA4A	Uncertain significance	criteria provided, single submitter
444182	NM_022367.4(SEMA4A):c.944C>T (p.Pro315Leu)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
450025	NM_022367.4(SEMA4A):c.1287C>G (p.His429Gln)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
501000	NM_022367.4(SEMA4A):c.1174A>C (p.Met392Leu)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
596486	NM_022367.4(SEMA4A):c.1451G>C (p.Gly484Ala)	SEMA4A	Uncertain significance	criteria provided, multiple submitters, no conflicts
599330	NM_022367.4(SEMA4A):c.1481G>A (p.Arg494Gln)	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	Supportive	Autosomal dominant	retinitis pigmentosa	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.