Cataract 31 multiple types

Summary

Cataract 31 multiple types (MONDO:0011547) is a disease caused by CHMP4B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CHMP4B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 31 multiple types
Mondo ID	MONDO:0011547
MeSH	C535343
OMIM	605387
DOID	DOID:0110265
UMLS	C1854311
MedGen	343089
GARD	0010227
Is cancer (heuristic)	no

Also known as: cataract 31, multiple types · CHMP4B early-onset non-syndromic cataract · CTRCT31 · early-onset non-syndromic cataract caused by mutation in CHMP4B

Data availability: 17 ClinVar variants · 3 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 › early-onset non-syndromic cataract › cataract 31 multiple types

Related subtypes (28): cataract 32 multiple types, cataract 8 multiple types, cataract 42, cataract 20 multiple types, cataract 6 multiple types, cataract 13 with adult I phenotype, cataract 5 multiple types, cataract 46 juvenile-onset, cataract 40, cataract 10 multiple types, cataract 14 multiple types, pulverulent cataract, cataract 26 multiple types, cataract 22 multiple types, cataract 21 multiple types, cataract 23, cataract 11 multiple types, cataract 33, cataract 17 multiple types, cataract 38, cataract 39 multiple types, cataract 15 multiple types, cataract 19 multiple types, cataract 43, cataract 44, cataract 45, early-onset partial cataract, total early-onset cataract

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

17 retrieved; paginated sample, class counts are floors:

6 likely benign, 4 uncertain significance, 2 pathogenic, 2 benign, 2 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1085	NM_176812.5(CHMP4B):c.386A>T (p.Asp129Val)	CHMP4B	Pathogenic	no assertion criteria provided
1086	NM_176812.5(CHMP4B):c.481G>A (p.Glu161Lys)	CHMP4B	Pathogenic	no assertion criteria provided
2841293	NM_176812.5(CHMP4B):c.200A>G (p.Gln67Arg)	CHMP4B	Likely pathogenic	criteria provided, single submitter
1304620	NM_176812.5(CHMP4B):c.460G>A (p.Gly154Arg)	CHMP4B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1473882	NM_176812.5(CHMP4B):c.481G>C (p.Glu161Gln)	CHMP4B	Uncertain significance	criteria provided, single submitter
2985085	NM_176812.5(CHMP4B):c.310G>A (p.Glu104Lys)	CHMP4B	Uncertain significance	criteria provided, single submitter
836756	NM_176812.5(CHMP4B):c.586T>G (p.Ser196Ala)	CHMP4B	Uncertain significance	criteria provided, single submitter
1105604	NM_176812.5(CHMP4B):c.240G>A (p.Ala80=)	CHMP4B	Likely benign	criteria provided, single submitter
1602809	NM_176812.5(CHMP4B):c.368+15G>A	CHMP4B	Likely benign	criteria provided, single submitter
2188536	NM_176812.5(CHMP4B):c.270G>A (p.Glu90=)	CHMP4B	Benign	criteria provided, single submitter
2190916	NM_176812.5(CHMP4B):c.450G>A (p.Ser150=)	CHMP4B	Benign	criteria provided, single submitter
3618332	NM_176812.5(CHMP4B):c.483+7A>G	CHMP4B	Likely benign	criteria provided, single submitter
4739349	NM_176812.5(CHMP4B):c.369-15C>T	CHMP4B	Likely benign	criteria provided, single submitter
4744529	NM_176812.5(CHMP4B):c.483+10T>G	CHMP4B	Likely benign	criteria provided, single submitter
4746511	NM_176812.5(CHMP4B):c.126C>T (p.Phe42=)	CHMP4B	Likely benign	criteria provided, single submitter
534366	NM_176812.5(CHMP4B):c.558C>T (p.Pro186=)	CHMP4B	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
772436	NM_176812.5(CHMP4B):c.191-5C>T	CHMP4B	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
CHMP4B	Strong	Autosomal dominant	cataract 31 multiple types	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CHMP4B	Orphanet:441447	Early-onset posterior subcapsular cataract
CHMP4B	Orphanet:98993	Early-onset posterior polar cataract

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
CHMP4B	HGNC:16171	ENSG00000101421	Q9H444	Charged multivesicular body protein 4b	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CHMP4B	Charged multivesicular body protein 4b	Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs.

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)
CHMP4B	Other/Unknown	no		Snf7_fam

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
ileal mucosa	1
tibialis anterior	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CHMP4B	259	ubiquitous	marker	ileal mucosa, upper arm skin, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHMP4B	3,043

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHMP4B	Q9H444	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
Translation of Replicase and Assembly of the Replication Transcription Complex	1	878.5×	0.004	CHMP4B
Translation of Replicase and Assembly of the Replication Transcription Complex	1	815.7×	0.004	CHMP4B
Pyroptosis	1	423.0×	0.004	CHMP4B
Budding and maturation of HIV virion	1	407.9×	0.004	CHMP4B
Endosomal Sorting Complex Required For Transport (ESCRT)	1	368.4×	0.004	CHMP4B
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.004	CHMP4B
Late endosomal microautophagy	1	326.3×	0.004	CHMP4B
Macroautophagy	1	115.3×	0.010	CHMP4B
HCMV Late Events	1	98.5×	0.010	CHMP4B

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
obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	1	3370.4×	0.002	CHMP4B
maintenance of lens transparency	1	2106.5×	0.002	CHMP4B
viral budding	1	1872.4×	0.002	CHMP4B
late endosome to vacuole transport via multivesicular body sorting pathway	1	1532.0×	0.002	CHMP4B
vesicle fusion with vacuole	1	1532.0×	0.002	CHMP4B
post-translational protein targeting to endoplasmic reticulum membrane	1	1404.3×	0.002	CHMP4B
multivesicular body-lysosome fusion	1	1404.3×	0.002	CHMP4B
viral budding from plasma membrane	1	1296.3×	0.002	CHMP4B
nervous system process	1	1203.7×	0.002	CHMP4B
vesicle budding from membrane	1	1123.5×	0.002	CHMP4B
exit from mitosis	1	1053.2×	0.002	CHMP4B
nuclear membrane reassembly	1	991.3×	0.002	CHMP4B
protein polymerization	1	991.3×	0.002	CHMP4B
late endosome to lysosome transport	1	991.3×	0.002	CHMP4B
viral budding via host ESCRT complex	1	802.5×	0.002	CHMP4B
multivesicular body sorting pathway	1	802.5×	0.002	CHMP4B
regulation of centrosome duplication	1	732.7×	0.002	CHMP4B
midbody abscission	1	732.7×	0.002	CHMP4B
regulation of mitotic spindle assembly	1	732.7×	0.002	CHMP4B
plasma membrane repair	1	581.1×	0.002	CHMP4B
nucleus organization	1	561.7×	0.002	CHMP4B
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	1	543.6×	0.002	CHMP4B
multivesicular body assembly	1	526.6×	0.002	CHMP4B
membrane fission	1	411.0×	0.003	CHMP4B
mitotic metaphase chromosome alignment	1	383.0×	0.003	CHMP4B
autophagosome maturation	1	351.1×	0.003	CHMP4B
mitotic cytokinesis	1	259.3×	0.004	CHMP4B
macroautophagy	1	240.7×	0.004	CHMP4B
autophagy	1	110.1×	0.009	CHMP4B
protein transport	1	43.9×	0.023	CHMP4B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHMP4B	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
CHMP4B	1	Binding:1

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	CHMP4B

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)
CHMP4B	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.