Cerulean cataract

Summary

Cerulean cataract (MONDO:0020374) is a disease with 5 cohort genes.

At a glance

• Cohort genes: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cerulean cataract
Mondo ID	MONDO:0020374
MeSH	C537955
Orphanet	98989
ICD-11	1188848969
SNOMED CT	204138006
UMLS	C0344523
MedGen	138007
GARD	0009508
Is cancer (heuristic)	no

Also known as: blue-dot cataract · cataract, congenital, blue dot type 1 · cataract, congenital, cerulean type 1

Data availability: 4 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

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 › early-onset partial cataract › cerulean cataract

Related subtypes (4): cataract 30, early-onset posterior subcapsular cataract, early-onset anterior polar cataract, early-onset zonular cataract

Subtypes (2): cataract 7, cataract 37

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 51 · Orphanet: 23 · 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
CRYBB2	Definitive	Autosomal dominant	cataract 3 multiple types	11
CRYGD	Definitive	Autosomal dominant	cataract 4 multiple types	9
MAF	Definitive	Autosomal dominant	cataract 21 multiple types	10
MIP	Definitive	Autosomal dominant	cataract 15 multiple types	10
TNPO1	Definitive	Autosomal dominant	cataract 15 multiple types	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYBB2	Orphanet:1377	Cataract-microcornea syndrome
CRYBB2	Orphanet:441447	Early-onset posterior subcapsular cataract
CRYBB2	Orphanet:98984	Pulverulent cataract
CRYBB2	Orphanet:98985	Early-onset sutural cataract
CRYBB2	Orphanet:98989	Cerulean cataract
CRYBB2	Orphanet:98991	Early-onset nuclear cataract
CRYBB2	Orphanet:98994	Total early-onset cataract
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
MAF	Orphanet:1272	Aymé-Gripp syndrome
MAF	Orphanet:1377	Cataract-microcornea syndrome
MAF	Orphanet:98984	Pulverulent cataract
MAF	Orphanet:98989	Cerulean cataract
MIP	Orphanet:441452	Early-onset lamellar cataract
MIP	Orphanet:98985	Early-onset sutural cataract
MIP	Orphanet:98989	Cerulean cataract
MIP	Orphanet:98991	Early-onset nuclear cataract
MIP	Orphanet:98993	Early-onset posterior polar cataract
MIP	Orphanet:98994	Total early-onset cataract

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CRYBB2	HGNC:2398	ENSG00000244752	P43320	Beta-crystallin B2	gencc
CRYGD	HGNC:2411	ENSG00000118231	P07320	Gamma-crystallin D	gencc
TNPO1	HGNC:6401	ENSG00000083312	Q92973	Transportin-1	gencc
MAF	HGNC:6776	ENSG00000178573	O75444	Transcription factor Maf	gencc
MIP	HGNC:7103	ENSG00000135517	P30301	Lens fiber major intrinsic protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYBB2	Beta-crystallin B2	Crystallins are the dominant structural components of the vertebrate eye lens.
CRYGD	Gamma-crystallin D	Crystallins are the dominant structural components of the vertebrate eye lens.
TNPO1	Transportin-1	Functions in nuclear protein import as nuclear transport receptor.
MAF	Transcription factor Maf	Acts as a transcriptional activator or repressor.
MIP	Lens fiber major intrinsic protein	Aquaporins form homotetrameric transmembrane channels, with each monomer independently mediating water transport across the plasma membrane along its osmotic gradient.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 4 · 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
Transcription factor	1	1.6×	0.476
Other/Unknown	4	1.4×	0.476

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRYBB2	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
CRYGD	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
TNPO1	Other/Unknown	no		Importin-beta_N, ARM-like, ARM-type_fold
MAF	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
MIP	Other/Unknown	no		MIP, MIP_CS, Aquaporin-like

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
primordial germ cell in gonad	2
gluteal muscle	1
trabecular bone tissue	1
triceps brachii	1
ventricular zone	1
caput epididymis	1
cauda epididymis	1
corpus epididymis	1
germinal epithelium of ovary	1
gingiva	1
jejunal mucosa	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYBB2	144	tissue_specific	yes	triceps brachii, gluteal muscle, trabecular bone tissue
CRYGD	60	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, ventricular zone
TNPO1	295	ubiquitous	marker	corpus epididymis, caput epididymis, cauda epididymis
MAF	290	ubiquitous	marker	jejunal mucosa, germinal epithelium of ovary, gingiva
MIP	91	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAF	4,111
TNPO1	3,147
MIP	2,496
CRYBB2	548
CRYGD	500

Intra-cohort edges

A	B	Sources
CRYBB2	MAF	string_interaction
CRYGD	MAF	string_interaction
CRYGD	MIP	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNPO1	Q92973	21
CRYGD	P07320	16
CRYBB2	P43320	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MIP	P30301	91.08
MAF	O75444	62.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Passive transport by Aquaporins	1	292.8×	0.018	MIP
RUNX2 regulates bone development	1	271.9×	0.018	MAF
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	1	211.5×	0.018	TNPO1
RUNX2 regulates osteoblast differentiation	1	152.3×	0.018	MAF
Postmitotic nuclear pore complex (NPC) reformation	1	135.9×	0.018	TNPO1
Aquaporin-mediated transport	1	122.8×	0.018	MIP
Transcriptional regulation by RUNX2	1	84.6×	0.022	MAF
Intraflagellar transport	1	66.8×	0.024	TNPO1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	48.8×	0.029	MAF
Transport of small molecules	1	8.4×	0.149	MIP
RNA Polymerase II Transcription	1	7.5×	0.151	MAF
Gene expression (Transcription)	1	6.0×	0.172	MAF
Generic Transcription Pathway	1	5.0×	0.186	MAF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 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	3	224.7×	3e-06	CRYBB2, CRYGD, MIP
lens fiber cell differentiation	2	421.3×	8e-05	CRYGD, MAF
visual perception	3	47.7×	1e-04	CRYBB2, CRYGD, MIP
gap junction-mediated intercellular transport	1	561.7×	0.008	MIP
maintenance of lens transparency	1	421.3×	0.009	MIP
homotypic cell-cell adhesion	1	337.0×	0.009	MIP
regulation of chondrocyte differentiation	1	280.9×	0.010	MAF
megakaryocyte differentiation	1	240.7×	0.010	MAF
water transport	1	198.3×	0.011	MIP
integrated stress response signaling	1	140.4×	0.013	MAF
cellular response to reactive oxygen species	1	82.2×	0.021	CRYGD
inner ear development	1	74.9×	0.021	MAF
response to nutrient	1	59.1×	0.025	MAF
protein import into nucleus	1	28.8×	0.046	TNPO1
in utero embryonic development	1	14.4×	0.082	MAF
transcription by RNA polymerase II	1	14.1×	0.082	MAF
positive regulation of gene expression	1	7.8×	0.137	MAF
negative regulation of transcription by RNA polymerase II	1	3.5×	0.266	MAF
regulation of transcription by RNA polymerase II	1	2.3×	0.361	MAF

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 3 of 5 evidence-associated genes (60%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CRYBB2	0	0
CRYGD	0	0
TNPO1	0	0
MAF	0	0
MIP	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
CRYBB2	9	Binding:9
CRYGD	9	Binding:9
TNPO1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	5	CRYBB2, CRYGD, TNPO1, MAF, MIP

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CRYBB2	9	—
CRYGD	9	—
TNPO1	7	—
MAF	0	—
MIP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.