Cataract 20 multiple types

Summary

Cataract 20 multiple types (MONDO:0007284) is a disease caused by CRYGS (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CRYGS (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 20 multiple types
Mondo ID	MONDO:0007284
OMIM	116100
DOID	DOID:0110240
UMLS	C0524524
MedGen	101117
GARD	0024544
Is cancer (heuristic)	no

Also known as: cataract (disease) caused by mutation in CRYGS · cataract 20, multiple types · CRYGS cataract (disease) · CTRCT20

Data availability: 35 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 20 multiple types

Related subtypes (28): cataract 32 multiple types, cataract 8 multiple types, cataract 42, 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 31 multiple types, 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

35 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 3 conflicting classifications of pathogenicity, 3 likely benign, 3 pathogenic, 2 benign, 1 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16936	NM_017541.4(CRYGS):c.53G>T (p.Gly18Val)	CRYGS	Pathogenic	criteria provided, single submitter
2734603	NM_017541.4(CRYGS):c.53G>A (p.Gly18Asp)	CRYGS	Pathogenic	criteria provided, single submitter
617601	NM_017541.4(CRYGS):c.124G>A (p.Val42Met)	CRYGS	Pathogenic	no assertion criteria provided
617600	NM_017541.4(CRYGS):c.116C>G (p.Ser39Cys)	CRYGS	Likely pathogenic	criteria provided, single submitter
1169654	NM_017541.4(CRYGS):c.77A>G (p.Asp26Gly)	CRYGS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1415793	NM_017541.4(CRYGS):c.215G>A (p.Arg72His)	CRYGS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
702786	NM_017541.4(CRYGS):c.39C>A (p.Asp13Glu)	CRYGS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009187	NM_017541.4(CRYGS):c.247T>C (p.Cys83Arg)	CRYGS	Uncertain significance	criteria provided, single submitter
1013944	NM_017541.4(CRYGS):c.248G>A (p.Cys83Tyr)	CRYGS	Uncertain significance	criteria provided, single submitter
1358112	NM_017541.4(CRYGS):c.224G>A (p.Gly75Asp)	CRYGS	Uncertain significance	criteria provided, single submitter
1400078	NM_017541.4(CRYGS):c.236G>A (p.Arg79His)	CRYGS	Uncertain significance	criteria provided, single submitter
1446817	NM_017541.4(CRYGS):c.32A>G (p.Tyr11Cys)	CRYGS	Uncertain significance	criteria provided, single submitter
1485465	NM_017541.4(CRYGS):c.62A>G (p.Tyr21Cys)	CRYGS	Uncertain significance	criteria provided, single submitter
1492005	NM_017541.4(CRYGS):c.269G>C (p.Ser90Thr)	CRYGS	Uncertain significance	criteria provided, single submitter
1806343	NM_017541.4(CRYGS):c.421G>T (p.Glu141Ter)	CRYGS	Uncertain significance	criteria provided, single submitter
2197267	NM_017541.4(CRYGS):c.107G>A (p.Arg36His)	CRYGS	Uncertain significance	criteria provided, multiple submitters, no conflicts
2440576	NM_017541.4(CRYGS):c.436C>T (p.Arg146Cys)	CRYGS	Uncertain significance	criteria provided, single submitter
2629550	NM_017541.4(CRYGS):c.374G>A (p.Arg125Gln)	CRYGS	Uncertain significance	criteria provided, multiple submitters, no conflicts
2772725	NM_017541.4(CRYGS):c.450C>A (p.Tyr150Ter)	CRYGS	Uncertain significance	criteria provided, single submitter
2810466	NM_017541.4(CRYGS):c.139T>C (p.Trp47Arg)	CRYGS	Uncertain significance	criteria provided, single submitter
2887086	NM_017541.4(CRYGS):c.502C>T (p.Pro168Ser)	CRYGS	Uncertain significance	criteria provided, single submitter
2997085	NM_017541.4(CRYGS):c.21+6T>C	CRYGS	Uncertain significance	criteria provided, single submitter
3698873	NM_017541.4(CRYGS):c.275G>A (p.Gly92Asp)	CRYGS	Uncertain significance	criteria provided, single submitter
3726901	NM_017541.4(CRYGS):c.169G>A (p.Gly57Arg)	CRYGS	Uncertain significance	criteria provided, single submitter
461820	NM_017541.4(CRYGS):c.253G>A (p.Ala85Thr)	CRYGS	Uncertain significance	criteria provided, single submitter
4726229	NM_017541.4(CRYGS):c.28T>G (p.Phe10Val)	CRYGS	Uncertain significance	criteria provided, single submitter
4728450	NM_017541.4(CRYGS):c.194G>T (p.Gly65Val)	CRYGS	Uncertain significance	criteria provided, single submitter
4812048	NM_017541.4(CRYGS):c.3G>A (p.Met1Ile)	CRYGS	Uncertain significance	criteria provided, single submitter
851976	NM_017541.4(CRYGS):c.299A>C (p.Glu100Ala)	CRYGS	Uncertain significance	criteria provided, multiple submitters, no conflicts
1169999	NM_017541.4(CRYGS):c.294C>A (p.Ile98=)	CRYGS	Benign	criteria provided, single submitter

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
CRYGS	Definitive	Autosomal dominant	cataract 20 multiple types	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYGS	Orphanet:441452	Early-onset lamellar cataract
CRYGS	Orphanet:98985	Early-onset sutural 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
CRYGS	HGNC:2417	ENSG00000213139	P22914	Gamma-crystallin S	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYGS	Gamma-crystallin S	Crystallins are the dominant structural components of the vertebrate eye lens.

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)
CRYGS	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin

Expression context

Cohort genes with no expression data: 0.

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
cerebellar cortex	1
cerebellar hemisphere	1
lens of camera-type eye	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYGS	179	tissue_specific	yes	lens of camera-type eye, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRYGS	513

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRYGS	P22914	12

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
lens development in camera-type eye	1	374.5×	0.004	CRYGS
morphogenesis of an epithelium	1	343.9×	0.004	CRYGS
visual perception	1	79.5×	0.013	CRYGS

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
CRYGS	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	CRYGS

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)
CRYGS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.