Cataract 50 with or without glaucoma

Summary

Cataract 50 with or without glaucoma (MONDO:0859382) is a disease caused by TRPM3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TRPM3 (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	cataract 50 with or without glaucoma
Mondo ID	MONDO:0859382
OMIM	620253
UMLS	C5830299
MedGen	1840935
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 › disorder of orbital region › eye disorder › lens disorder › cataract › cataract 50 with or without glaucoma

Related subtypes (28): immature cataract, diabetic cataract, mature cataract, tetanic cataract, myotonic cataract, senile cataract, diabetes mellitus type 2 associated cataract, cataract 4 multiple types, cataract 29, cataract 1 multiple types, early-onset non-syndromic cataract, cataract 3 multiple types, cataract 9 multiple types, cataract 28, cataract 18, cataract 12 multiple types, cataract 34 multiple types, cataract 36, bhaskar jagannathan syndrome, autosomal dominant cataract, craniostenosis cataract, Kozlowski Rafinski Klicharska syndrome, cataract 49, cataract 48, hypermature cataract, nuclear cataract, cortical cataract, cataract 2, multiple types

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:

3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3238765	NM_001366145.2(TRPM3):c.4208C>T (p.Pro1403Leu)	KLF9-DT	Uncertain significance	criteria provided, single submitter
2443699	NM_001366145.2(TRPM3):c.195A>G (p.Ile65Met)	TRPM3	Uncertain significance	criteria provided, single submitter
3183318	NM_001366145.2(TRPM3):c.2878G>A (p.Ala960Thr)	TRPM3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · 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
TRPM3	Strong	Autosomal dominant	cataract 50 with or without glaucoma	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPM3	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRPM3	HGNC:17992	ENSG00000083067	Q9HCF6	Transient receptor potential cation channel subfamily M member 3	gencc,clinvar
KLF9-DT	HGNC:54815			KLF9 divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPM3	Transient receptor potential cation channel subfamily M member 3	Constitutively active, non-selective divalent cation-conducting channel that is permeable to Ca(2+), Mn(2+), and Mg(2+), with a high permeability for Ca(2+).

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
Ion channel	1	55.8×	0.036
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPM3	Ion channel	yes		Ion_trans_dom, TRPM_tetra, TRPM_tetra_sf
KLF9-DT	Other/Unknown	no

Expression context

Cohort genes with no expression data: 1.

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	1

Top tissues across cohort

Tissue	Cohort genes
dorsal motor nucleus of vagus nerve	1
medial globus pallidus	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPM3	193	broad	marker	pigmented layer of retina, dorsal motor nucleus of vagus nerve, medial globus pallidus
KLF9-DT

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPM3	1,184
KLF9-DT	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRPM3	Q9HCF6	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
TRP channels	1	407.9×	0.002	TRPM3

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
monoatomic cation transport	1	766.0×	0.003	TRPM3
zinc ion transmembrane transport	1	702.2×	0.003	TRPM3
monoatomic cation transmembrane transport	1	624.1×	0.003	TRPM3
protein homotetramerization	1	237.3×	0.006	TRPM3
calcium ion transmembrane transport	1	210.7×	0.006	TRPM3
calcium ion transport	1	181.2×	0.006	TRPM3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRPM3	0	0
KLF9-DT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TRPM3	2	Binding:2

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	1	TRPM3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	KLF9-DT

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)
TRPM3	2	—
KLF9-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.