Cataract 4 multiple types

Summary

Cataract 4 multiple types (MONDO:0007281) is a disease caused by CRYGD (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CRYGD (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 38

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 4 multiple types
Mondo ID	MONDO:0007281
OMIM	115700
DOID	DOID:0110234
UMLS	C3540850
MedGen	761925
GARD	0001144
Is cancer (heuristic)	no

Also known as: cataract (disease) caused by mutation in CRYGD · cataract 4, multiple types · CRYGD cataract (disease) · CTRCT4

Data availability: 38 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 › cataract 4 multiple types

Related subtypes (28): immature cataract, diabetic cataract, mature cataract, tetanic cataract, myotonic cataract, senile cataract, diabetes mellitus type 2 associated cataract, 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, cataract 50 with or without glaucoma

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

38 retrieved; paginated sample, class counts are floors:

11 benign, 9 uncertain significance, 6 pathogenic, 4 benign/likely benign, 3 likely pathogenic, 3 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
16937	NM_006891.4(CRYGD):c.43C>T (p.Arg15Cys)	CRYGD	Pathogenic	criteria provided, multiple submitters, no conflicts
16938	NM_006891.4(CRYGD):c.176G>A (p.Arg59His)	CRYGD	Pathogenic	criteria provided, single submitter
16939	NM_006891.4(CRYGD):c.109C>A (p.Arg37Ser)	CRYGD	Pathogenic	criteria provided, single submitter
16941	NM_006891.4(CRYGD):c.470G>A (p.Trp157Ter)	CRYGD	Pathogenic	no assertion criteria provided
16942	NM_006891.4(CRYGD):c.70C>T (p.Pro24Ser)	CRYGD	Pathogenic	no assertion criteria provided
574060	NM_006891.4(CRYGD):c.418C>T (p.Arg140Ter)	CRYGD	Pathogenic	criteria provided, multiple submitters, no conflicts
16940	NM_006891.4(CRYGD):c.70C>A (p.Pro24Thr)	LOC100507443	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217353	NM_006891.4(CRYGD):c.448dup (p.Asp150fs)	LOC100507443	Likely pathogenic	criteria provided, single submitter
4687996	NM_006891.4(CRYGD):c.392G>A (p.Trp131Ter)	LOC100507443	Likely pathogenic	criteria provided, single submitter
68462	NM_006891.4(CRYGD):c.402C>A (p.Tyr134Ter)	LOC100507443	Likely pathogenic	criteria provided, single submitter
333871	NM_006891.4(CRYGD):c.264C>G (p.His88Gln)	CRYGD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
333874	NM_006891.4(CRYGD):c.168C>G (p.Tyr56Ter)	CRYGD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
896706	NM_006891.4(CRYGD):c.479C>T (p.Thr160Met)	CRYGD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1329992	NM_006891.4(CRYGD):c.233C>T (p.Ser78Phe)	CRYGD	Uncertain significance	no assertion criteria provided
2574046	NM_006891.4(CRYGD):c.290A>T (p.Asp97Val)	CRYGD	Uncertain significance	criteria provided, single submitter
3068122	NM_006891.4(CRYGD):c.173T>G (p.Leu58Arg)	CRYGD	Uncertain significance	criteria provided, single submitter
333868	NM_006891.4(CRYGD):c.482A>G (p.Asn161Ser)	CRYGD	Uncertain significance	criteria provided, multiple submitters, no conflicts
3901927	NM_006891.4(CRYGD):c.304dup (p.Met102fs)	CRYGD	Uncertain significance	criteria provided, single submitter
333870	NM_006891.4(CRYGD):c.295A>G (p.Arg99Gly)	LOC100507443	Uncertain significance	criteria provided, single submitter
895355	NM_006891.4(CRYGD):c.-33A>G	LOC100507443	Uncertain significance	criteria provided, multiple submitters, no conflicts
896707	NM_006891.4(CRYGD):c.333T>C (p.Cys111=)	LOC100507443	Uncertain significance	criteria provided, single submitter
897167	NM_006891.4(CRYGD):c.252C>T (p.His84=)	LOC100507443	Uncertain significance	criteria provided, single submitter
260059	NM_006891.4(CRYGD):c.*12T>C	CRYGD	Benign	criteria provided, multiple submitters, no conflicts
260060	NM_006891.4(CRYGD):c.189T>C (p.Tyr63=)	CRYGD	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
260061	NM_006891.4(CRYGD):c.285A>G (p.Arg95=)	CRYGD	Benign	criteria provided, multiple submitters, no conflicts
260062	NM_006891.4(CRYGD):c.51T>C (p.Tyr17=)	CRYGD	Benign	criteria provided, multiple submitters, no conflicts
333867	NM_006891.4(CRYGD):c.499C>T (p.Leu167=)	CRYGD	Benign	criteria provided, multiple submitters, no conflicts
333869	NM_006891.4(CRYGD):c.376G>A (p.Val126Met)	CRYGD	Benign	criteria provided, multiple submitters, no conflicts
333872	NM_006891.4(CRYGD):c.252+10T>A	CRYGD	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
333873	NM_006891.4(CRYGD):c.252+7A>G	CRYGD	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 6 · 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
CRYGD	Definitive	Autosomal dominant	cataract 4 multiple types	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYGD	Orphanet:1377	Cataract-microcornea syndrome
CRYGD	Orphanet:441452	Early-onset lamellar cataract
CRYGD	Orphanet:98984	Pulverulent cataract
CRYGD	Orphanet:98989	Cerulean cataract
CRYGD	Orphanet:98990	Coralliform cataract
CRYGD	Orphanet:98991	Early-onset nuclear 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
CRYGD	HGNC:2411	ENSG00000118231	P07320	Gamma-crystallin D	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYGD	Gamma-crystallin D	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)
CRYGD	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin

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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYGD	60	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRYGD	500

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRYGD	P07320	16

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 fiber cell differentiation	1	1053.2×	0.004	CRYGD
cellular response to reactive oxygen species	1	411.0×	0.004	CRYGD
lens development in camera-type eye	1	374.5×	0.004	CRYGD
visual perception	1	79.5×	0.013	CRYGD

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
CRYGD	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
CRYGD	9	Binding:9

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	CRYGD

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)
CRYGD	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.