Cataract 46 juvenile-onset

Summary

Cataract 46 juvenile-onset (MONDO:0008925) is a disease caused by LEMD2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LEMD2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 46 juvenile-onset
Mondo ID	MONDO:0008925
MeSH	C538286
OMIM	212500
Orphanet	98987
DOID	DOID:0110243
UMLS	C0220721
MedGen	113102
GARD	0001150
Is cancer (heuristic)	no

Also known as: cataract Hutterite type · CTRCT46 · early-onset non-syndromic cataract caused by mutation in LEMD2 · LEMD2 early-onset non-syndromic cataract

Data availability: 2 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 › early-onset non-syndromic cataract › cataract 46 juvenile-onset

Related subtypes (28): cataract 32 multiple types, cataract 8 multiple types, cataract 42, cataract 20 multiple types, cataract 6 multiple types, cataract 13 with adult I phenotype, cataract 5 multiple types, 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

2 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
235192	NM_181336.4(LEMD2):c.38T>G (p.Leu13Arg)	LEMD2	Pathogenic	criteria provided, single submitter
2308600	NM_181336.4(LEMD2):c.1430C>T (p.Thr477Met)	LEMD2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 3 · 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
LEMD2	Strong	Autosomal recessive	cataract 46 juvenile-onset	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LEMD2	Orphanet:441447	Early-onset posterior subcapsular cataract
LEMD2	Orphanet:659873	Wormian bones-micrognathia-abnormal dentition-progeroid syndrome
LEMD2	Orphanet:98994	Total early-onset 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
LEMD2	HGNC:21244	ENSG00000161904	Q8NC56	LEM domain-containing protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LEMD2	LEM domain-containing protein 2	Nuclear lamina-associated inner nuclear membrane protein that is involved in nuclear structure organization, maintenance of nuclear envelope (NE) integrity and NE reformation after mitosis.

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)
LEMD2	Other/Unknown	no		LEM_dom, LEM/LEM-like_dom_sf, Man1/Src1-like_C

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LEMD2	186	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LEMD2	2,340

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LEMD2	Q8NC56	71.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Depolymerization of the Nuclear Lamina	1	761.3×	0.006	LEMD2
Initiation of Nuclear Envelope (NE) Reformation	1	601.0×	0.006	LEMD2
Nuclear Envelope Breakdown	1	456.8×	0.006	LEMD2
Mitotic Prophase	1	368.4×	0.006	LEMD2
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.006	LEMD2
Nuclear Envelope (NE) Reassembly	1	292.8×	0.006	LEMD2
Mitotic Metaphase and Anaphase	1	96.8×	0.014	LEMD2
Mitotic Anaphase	1	96.8×	0.014	LEMD2
M Phase	1	66.0×	0.019	LEMD2
Cell Cycle, Mitotic	1	48.2×	0.023	LEMD2
Cell Cycle	1	36.0×	0.028	LEMD2

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
heart formation	1	3370.4×	0.002	LEMD2
nuclear membrane organization	1	2407.4×	0.002	LEMD2
nuclear envelope organization	1	991.3×	0.003	LEMD2
protein localization to chromatin	1	581.1×	0.003	LEMD2
skeletal muscle cell differentiation	1	343.9×	0.004	LEMD2
negative regulation of MAPK cascade	1	300.9×	0.004	LEMD2
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	263.3×	0.004	LEMD2
neurogenesis	1	208.1×	0.005	LEMD2

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
LEMD2	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	LEMD2

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)
LEMD2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.