Cataract 1 multiple types

Summary

Cataract 1 multiple types (MONDO:0007285) is a disease caused by GJA8 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: GJA8 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 197

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 1 multiple types
Mondo ID	MONDO:0007285
MeSH	C566158
OMIM	116200
DOID	DOID:0110231
UMLS	C1861828
MedGen	349374
GARD	0015047
Is cancer (heuristic)	no

Also known as: cataract (disease) caused by mutation in GJA8 · cataract 1, multiple types · cataract 1, multiple types, with or without microcornea · CTRCT1 · GJA8 cataract (disease)

Data availability: 197 ClinVar variants · 4 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 1 multiple types

Related subtypes (28): immature cataract, diabetic cataract, mature cataract, tetanic cataract, myotonic cataract, senile cataract, diabetes mellitus type 2 associated cataract, cataract 4 multiple types, cataract 29, 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

197 retrieved; paginated sample, class counts are floors:

95 uncertain significance, 25 conflicting classifications of pathogenicity, 23 likely pathogenic, 19 likely benign, 15 pathogenic, 11 pathogenic/likely pathogenic, 5 benign/likely benign, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065589	NM_005267.5(GJA8):c.64G>A (p.Gly22Ser)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1410982	NM_005267.5(GJA8):c.135G>T (p.Trp45Cys)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1484682	NM_005267.5(GJA8):c.143A>G (p.Glu48Gly)	GJA8	Pathogenic	criteria provided, single submitter
1684590	NM_005267.5(GJA8):c.263C>T (p.Pro88Leu)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704073	NM_005267.5(GJA8):c.130G>A (p.Val44Met)	GJA8	Pathogenic	criteria provided, multiple submitters, no conflicts
2030122	NM_005267.5(GJA8):c.94T>G (p.Phe32Val)	GJA8	Pathogenic	criteria provided, single submitter
2103996	NM_005267.5(GJA8):c.137G>A (p.Gly46Glu)	GJA8	Pathogenic	criteria provided, multiple submitters, no conflicts
217335	NM_005267.5(GJA8):c.134G>C (p.Trp45Ser)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2425333	NC_000001.10:g.(?146714354)(147381384_?)del	GJA8	Pathogenic	criteria provided, single submitter
2574784	NM_005267.5(GJA8):c.178G>A (p.Gly60Ser)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280147	NM_005267.5(GJA8):c.139G>C (p.Asp47His)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2814004	NM_005267.5(GJA8):c.191T>C (p.Val64Ala)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3236402	NM_005267.5(GJA8):c.196T>G (p.Tyr66Asp)	GJA8	Pathogenic	criteria provided, single submitter
3253671	NM_005267.5(GJA8):c.773C>T (p.Ser258Phe)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4768435	NM_005267.5(GJA8):c.136G>C (p.Gly46Arg)	GJA8	Pathogenic	criteria provided, single submitter
574353	NM_005267.5(GJA8):c.153C>G (p.Asp51Glu)	GJA8	Pathogenic	criteria provided, single submitter
650108	NM_005267.5(GJA8):c.262C>G (p.Pro88Ala)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
655801	NM_005267.5(GJA8):c.196T>C (p.Tyr66His)	GJA8	Pathogenic	criteria provided, single submitter
833373	NC_000001.10:g.(?147380063)(147381404_?)del	GJA8	Pathogenic	criteria provided, single submitter
842078	NM_005267.5(GJA8):c.176C>T (p.Pro59Leu)	GJA8	Pathogenic	criteria provided, single submitter
845873	NM_005267.5(GJA8):c.134G>T (p.Trp45Leu)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
850845	NM_005267.5(GJA8):c.197A>C (p.Tyr66Ser)	GJA8	Pathogenic	criteria provided, single submitter
861618	NM_005267.5(GJA8):c.602A>G (p.Glu201Gly)	GJA8	Pathogenic	criteria provided, single submitter
8721	NM_005267.5(GJA8):c.262C>T (p.Pro88Ser)	GJA8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8727	NM_005267.5(GJA8):c.139G>A (p.Asp47Asn)	GJA8	Pathogenic	criteria provided, single submitter
938578	NM_005267.5(GJA8):c.197A>G (p.Tyr66Cys)	GJA8	Pathogenic	criteria provided, single submitter
1328353	NM_005267.5(GJA8):c.227G>A (p.Arg76His)	GJA8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1684591	NM_005267.5(GJA8):c.263C>A (p.Pro88Gln)	GJA8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
217331	NM_005267.5(GJA8):c.89dup (p.Ile31fs)	GJA8	Likely pathogenic	criteria provided, single submitter
2444115	NM_005267.5(GJA8):c.116C>A (p.Thr39Lys)	GJA8	Likely pathogenic	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
GJA8	Definitive	Autosomal dominant	cataract 1 multiple types	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GJA8	HGNC:4281	ENSG00000121634	P48165	Gap junction alpha-8 protein	gencc,clinvar
ACP6	HGNC:29609	ENSG00000162836	Q9NPH0	Lysophosphatidic acid phosphatase type 6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GJA8	Gap junction alpha-8 protein	Structural component of eye lens gap junctions.
ACP6	Lysophosphatidic acid phosphatase type 6	Hydrolyzes lysophosphatidic acid (LPA) containing a medium length fatty acid chain to the corresponding monoacylglycerol.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Phosphatase	1	42.0×	0.047
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GJA8	Other/Unknown	no		Connexin, Connexin50_C, Connexin_N
ACP6	Phosphatase	yes	3.1.3.106	His_Pase_clade-2, His_PPase_superfam, Acid_Pase_AS

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
frontal pole	1
paraflocculus	1
mucosa of stomach	1
pancreatic ductal cell	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GJA8	17	tissue_specific	yes	buccal mucosa cell, frontal pole, paraflocculus
ACP6	257	ubiquitous	marker	right uterine tube, pancreatic ductal cell, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GJA8	1,149
ACP6	785

Intra-cohort edges

A	B	Sources
ACP6	GJA8	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACP6	Q9NPH0	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GJA8	P48165	65.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of PA	1	146.4×	0.007	ACP6
Gap junction assembly	1	146.4×	0.007	GJA8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
lysobisphosphatidic acid metabolic process	1	4213.0×	0.002	ACP6
gap junction-mediated intercellular transport	1	1404.3×	0.002	GJA8
phosphatidic acid biosynthetic process	1	255.3×	0.008	ACP6
lens development in camera-type eye	1	187.2×	0.008	GJA8
phospholipid metabolic process	1	172.0×	0.008	ACP6
hematopoietic progenitor cell differentiation	1	118.7×	0.010	ACP6
cell-cell signaling	1	34.8×	0.029	GJA8

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
GJA8	0	0
ACP6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACP6	3.1.3.106	2-lysophosphatidate phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	ACP6
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GJA8

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GJA8	0	—
ACP6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.