Exudative vitreoretinopathy 5

Summary

Exudative vitreoretinopathy 5 (MONDO:0013218) is a disease caused by TSPAN12 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TSPAN12 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 67

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	exudative vitreoretinopathy 5
Mondo ID	MONDO:0013218
MeSH	C567648
OMIM	613310
DOID	DOID:0111408
UMLS	C2750079
MedGen	412872
GARD	0015646
Is cancer (heuristic)	no

Also known as: EVR5 · exudative vitreoretinopathy 5 · exudative vitreoretinopathy caused by mutation in TSPAN12 · exudative vitreoretinopathy type 5 · TSPAN12 exudative vitreoretinopathy

Data availability: 67 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal vascular disorder › exudative vitreoretinopathy › TSPAN12-related exudative vitreoretinopathy › exudative vitreoretinopathy 5

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

67 retrieved; paginated sample, class counts are floors:

28 uncertain significance, 13 benign, 12 pathogenic, 6 conflicting classifications of pathogenicity, 5 likely pathogenic, 2 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1172699	NM_012338.4(TSPAN12):c.301dup (p.Leu101fs)	TSPAN12	Pathogenic	criteria provided, multiple submitters, no conflicts
126503	NM_012338.4(TSPAN12):c.413A>G (p.Tyr138Cys)	TSPAN12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126504	NM_012338.4(TSPAN12):c.67-1G>C	TSPAN12	Pathogenic	criteria provided, single submitter
126506	NM_012338.4(TSPAN12):c.285+1G>A	TSPAN12	Pathogenic	no assertion criteria provided
1334684	NM_012338.4(TSPAN12):c.176_179del (p.Tyr59fs)	TSPAN12	Pathogenic	criteria provided, multiple submitters, no conflicts
1687582	NM_012338.4(TSPAN12):c.345T>G (p.Tyr115Ter)	TSPAN12	Pathogenic	criteria provided, single submitter
236067	NM_012338.4(TSPAN12):c.542G>T (p.Cys181Phe)	TSPAN12	Pathogenic	criteria provided, multiple submitters, no conflicts
319	NM_012338.4(TSPAN12):c.709G>C (p.Ala237Pro)	TSPAN12	Pathogenic	no assertion criteria provided
321	NM_012338.4(TSPAN12):c.212_218dup (p.Phe73fs)	TSPAN12	Pathogenic	criteria provided, single submitter
322	NM_012338.4(TSPAN12):c.419T>A (p.Leu140Ter)	TSPAN12	Pathogenic	no assertion criteria provided
323	NM_012338.4(TSPAN12):c.361-5_361-1del	TSPAN12	Pathogenic	no assertion criteria provided
3382835	NM_012338.4(TSPAN12):c.11_14dup (p.Asp5fs)	TSPAN12	Pathogenic	criteria provided, single submitter
3393527	C181F	TSPAN12	Pathogenic	no assertion criteria provided
804349	NM_012338.4(TSPAN12):c.566G>A (p.Cys189Tyr)	TSPAN12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687611	NM_012338.4(TSPAN12):c.612+1G>T	TSPAN12	Likely pathogenic	criteria provided, single submitter
2921267	NM_012338.4(TSPAN12):c.66+1del	TSPAN12	Likely pathogenic	criteria provided, single submitter
324	NM_012338.4(TSPAN12):c.302T>A (p.Leu101His)	TSPAN12	Likely pathogenic	criteria provided, single submitter
373552	NM_012338.4(TSPAN12):c.67-2A>G	TSPAN12	Likely pathogenic	criteria provided, multiple submitters, no conflicts
931107	NM_012338.4(TSPAN12):c.459dup (p.Gln154fs)	TSPAN12	Likely pathogenic	criteria provided, single submitter
126505	NM_012338.4(TSPAN12):c.146C>T (p.Thr49Met)	TSPAN12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1719387	NM_012338.4(TSPAN12):c.502T>C (p.Trp168Arg)	TSPAN12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
358769	NM_012338.4(TSPAN12):c.-246T>G	TSPAN12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
910280	NM_012338.4(TSPAN12):c.825A>G (p.Ser275=)	TSPAN12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911499	NM_012338.4(TSPAN12):c.484G>A (p.Val162Ile)	TSPAN12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911500	NM_012338.4(TSPAN12):c.147G>A (p.Thr49=)	TSPAN12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030249	NM_012338.4(TSPAN12):c.667C>A (p.Leu223Met)	TSPAN12	Uncertain significance	criteria provided, multiple submitters, no conflicts
1687193	NM_012338.4(TSPAN12):c.476G>T (p.Cys159Phe)	TSPAN12	Uncertain significance	criteria provided, single submitter
1699371	NM_012338.4(TSPAN12):c.214T>C (p.Cys72Arg)	TSPAN12	Uncertain significance	criteria provided, single submitter
1705323	NM_012338.4(TSPAN12):c.283T>C (p.Trp95Arg)	TSPAN12	Uncertain significance	criteria provided, single submitter
1705403	NM_012338.4(TSPAN12):c.32G>A (p.Arg11His)	TSPAN12	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
TSPAN12	Definitive	Autosomal dominant	exudative vitreoretinopathy 5	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSPAN12	Orphanet:891	Familial exudative vitreoretinopathy

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
TSPAN12	HGNC:21641	ENSG00000106025	O95859	Tetraspanin-12	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSPAN12	Tetraspanin-12	Regulator of cell surface receptor signal transduction.

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)
TSPAN12	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin

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
nephron tubule	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSPAN12	267	ubiquitous	marker	oocyte, nephron tubule, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSPAN12	686

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TSPAN12	O95859	1

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
Norrin signaling pathway	1	3370.4×	0.002	TSPAN12
retina layer formation	1	648.1×	0.004	TSPAN12
maintenance of blood-brain barrier	1	481.5×	0.004	TSPAN12
regulation of angiogenesis	1	421.3×	0.004	TSPAN12
cell surface receptor signaling pathway	1	64.1×	0.016	TSPAN12
angiogenesis	1	62.4×	0.016	TSPAN12

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
TSPAN12	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	TSPAN12

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)
TSPAN12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.