Early-onset sutural cataract

Summary

Early-onset sutural cataract (MONDO:0020372) is a disease with 7 cohort genes.

At a glance

• Cohort genes: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	early-onset sutural cataract
Mondo ID	MONDO:0020372
Orphanet	98985
GARD	0016885
Is cancer (heuristic)	no

Also known as: early-onset cataract with Y-shaped suture opacities

Data availability: 6 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

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 › early-onset zonular cataract › early-onset sutural cataract

Related subtypes (2): cataract 16 multiple types, early-onset nuclear cataract

Subtypes (1): cataract 25

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: 62 · Orphanet: 28 · 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
BFSP2	Definitive	Autosomal dominant	cataract 12 multiple types	9
CRYBA1	Definitive	Autosomal dominant	cataract 10 multiple types	7
CRYBB2	Definitive	Autosomal dominant	cataract 3 multiple types	11
CRYGS	Definitive	Autosomal dominant	cataract 20 multiple types	5
GJA8	Definitive	Autosomal dominant	cataract 1 multiple types	9
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
BFSP2	Orphanet:441452	Early-onset lamellar cataract
BFSP2	Orphanet:98984	Pulverulent cataract
BFSP2	Orphanet:98985	Early-onset sutural cataract
CRYBA1	Orphanet:441452	Early-onset lamellar cataract
CRYBA1	Orphanet:98985	Early-onset sutural cataract
CRYBA1	Orphanet:98991	Early-onset nuclear cataract
CRYBA1	Orphanet:98993	Early-onset posterior polar cataract
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
CRYGS	Orphanet:441452	Early-onset lamellar cataract
CRYGS	Orphanet:98985	Early-onset sutural cataract
GJA8	Orphanet:1377	Cataract-microcornea syndrome
GJA8	Orphanet:91490	Isolated congenital sclerocornea
GJA8	Orphanet:98984	Pulverulent cataract
GJA8	Orphanet:98985	Early-onset sutural cataract
GJA8	Orphanet:98991	Early-onset nuclear cataract
GJA8	Orphanet:98994	Total early-onset 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

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BFSP2	HGNC:1041	ENSG00000170819	Q13515	Phakinin	gencc
CRYBA1	HGNC:2394	ENSG00000108255	P05813	Beta-crystallin A3	gencc
CRYBB2	HGNC:2398	ENSG00000244752	P43320	Beta-crystallin B2	gencc
CRYGS	HGNC:2417	ENSG00000213139	P22914	Gamma-crystallin S	gencc
GJA8	HGNC:4281	ENSG00000121634	P48165	Gap junction alpha-8 protein	gencc
TNPO1	HGNC:6401	ENSG00000083312	Q92973	Transportin-1	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)
BFSP2	Phakinin	Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA.
CRYBA1	Beta-crystallin A3	Crystallins are the dominant structural components of the vertebrate eye lens.
CRYBB2	Beta-crystallin B2	Crystallins are the dominant structural components of the vertebrate eye lens.
CRYGS	Gamma-crystallin S	Crystallins are the dominant structural components of the vertebrate eye lens.
GJA8	Gap junction alpha-8 protein	Structural component of eye lens gap junctions.
TNPO1	Transportin-1	Functions in nuclear protein import as nuclear transport receptor.
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: 0 · Unknown: 7 · 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	7	1.8×	0.017

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BFSP2	Other/Unknown	no		Keratin_I, IF_rod_dom
CRYBA1	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
CRYBB2	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
CRYGS	Other/Unknown	no		Beta/gamma_crystallin, G_crystallin-like, Beta/Gamma-Crystallin
GJA8	Other/Unknown	no		Connexin, Connexin50_C, Connexin_N
TNPO1	Other/Unknown	no		Importin-beta_N, ARM-like, ARM-type_fold
MIP	Other/Unknown	no		MIP, MIP_CS, Aquaporin-like

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)	1
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lens of camera-type eye	3
male germ line stem cell (sensu Vertebrata) in testis	3
primordial germ cell in gonad	3
gluteal muscle	1
trabecular bone tissue	1
triceps brachii	1
cerebellar cortex	1
cerebellar hemisphere	1
buccal mucosa cell	1
frontal pole	1
paraflocculus	1
caput epididymis	1
cauda epididymis	1
corpus epididymis	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BFSP2	111	tissue_specific	yes	lens of camera-type eye, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
CRYBA1	138	tissue_specific	yes	lens of camera-type eye, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
CRYBB2	144	tissue_specific	yes	triceps brachii, gluteal muscle, trabecular bone tissue
CRYGS	179	tissue_specific	yes	lens of camera-type eye, cerebellar hemisphere, cerebellar cortex
GJA8	17	tissue_specific	yes	buccal mucosa cell, frontal pole, paraflocculus
TNPO1	295	ubiquitous	marker	corpus epididymis, caput epididymis, cauda epididymis
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: 11.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNPO1	3,147
MIP	2,496
BFSP2	1,203
GJA8	1,149
CRYBA1	925
CRYBB2	548
CRYGS	513

Intra-cohort edges

A	B	Sources
BFSP2	CRYBA1	string_interaction
BFSP2	CRYBB2	string_interaction
BFSP2	CRYGS	string_interaction
BFSP2	GJA8	string_interaction
BFSP2	MIP	string_interaction
CRYBA1	CRYBB2	biogrid_interaction, intact
CRYBA1	GJA8	string_interaction
CRYBB2	GJA8	string_interaction
CRYGS	GJA8	string_interaction
CRYGS	MIP	string_interaction
GJA8	MIP	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TNPO1	Q92973	21
CRYGS	P22914	12
CRYBB2	P43320	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MIP	P30301	91.08
CRYBA1	P05813	88.27
BFSP2	Q13515	78.15
GJA8	P48165	65.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 7 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×	0.014	MIP
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	1	211.5×	0.014	TNPO1
Postmitotic nuclear pore complex (NPC) reformation	1	135.9×	0.014	TNPO1
Aquaporin-mediated transport	1	122.8×	0.014	MIP
Gap junction assembly	1	97.6×	0.014	GJA8
Intraflagellar transport	1	66.8×	0.017	TNPO1
Transport of small molecules	1	8.4×	0.115	MIP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 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	5	267.5×	4e-11	CRYBA1, CRYBB2, CRYGS, GJA8, MIP
visual perception	5	56.8×	6e-08	BFSP2, CRYBA1, CRYBB2, CRYGS, MIP
gap junction-mediated intercellular transport	2	802.5×	1e-05	GJA8, MIP
maintenance of lens transparency	1	300.9×	0.011	MIP
lens fiber cell development	1	300.9×	0.011	BFSP2
positive regulation of anoikis	1	267.5×	0.011	CRYBA1
homotypic cell-cell adhesion	1	240.7×	0.011	MIP
water transport	1	141.6×	0.017	MIP
negative regulation of TOR signaling	1	80.2×	0.026	CRYBA1
negative regulation of cytokine production	1	73.0×	0.026	CRYBA1
cell maturation	1	63.4×	0.027	BFSP2
morphogenesis of an epithelium	1	49.1×	0.032	CRYGS
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	37.6×	0.034	CRYBA1
phagocytosis	1	34.4×	0.034	CRYBA1
regulation of autophagy	1	34.4×	0.034	CRYBA1
intermediate filament organization	1	34.4×	0.034	BFSP2
negative regulation of ERK1 and ERK2 cascade	1	30.9×	0.036	CRYBA1
protein import into nucleus	1	20.6×	0.050	TNPO1
cell-cell signaling	1	9.9×	0.096	GJA8

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 7

Druggability breadth: 2 of 7 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BFSP2	0	0
CRYBA1	0	0
CRYBB2	0	0
CRYGS	0	0
GJA8	0	0
TNPO1	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
TNPO1	7	Binding:7

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; 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	7	BFSP2, CRYBA1, CRYBB2, CRYGS, GJA8, TNPO1, MIP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BFSP2	0	—
CRYBA1	0	—
CRYBB2	9	—
CRYGS	0	—
GJA8	0	—
TNPO1	7	—
MIP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.