Cataract 40

Summary

Cataract 40 (MONDO:0010544) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 40
Mondo ID	MONDO:0010544
MeSH	C535338
OMIM	302200
DOID	DOID:0110272
UMLS	C4049004
MedGen	886621
GARD	0008278
Is cancer (heuristic)	no

Also known as: cataract 40 · cataract 40 with or without microcornea · cataract 40, X-linked · cataract congenital X-linked · cataract type 40 · cataract, congenital, with microcornea or slight microphthalmia · CTRCT40 · early-onset non-syndromic cataract caused by mutation in NHS · NHS early-onset non-syndromic cataract

Data availability: 20 ClinVar variants.

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 40

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 46 juvenile-onset, 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

20 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 5 pathogenic, 5 likely pathogenic, 3 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
11030	NM_001291867.2(NHS):c.566-154020_566-149209del	LOC101928389	Pathogenic	no assertion criteria provided
11025	NM_001291867.2(NHS):c.1180C>T (p.Arg394Ter)	NHS	Pathogenic	criteria provided, multiple submitters, no conflicts
11029	NCBI36/hg18 Xp22.13(chrX:17104696-17800261)x3	NHS	Pathogenic	no assertion criteria provided
2574153	NM_001291867.2(NHS):c.853-2A>C	NHS	Pathogenic	criteria provided, single submitter
3382893	NM_001291867.2(NHS):c.719-1G>T	NHS	Pathogenic	criteria provided, single submitter
3062267	NM_001291867.2(NHS):c.1108+1G>A	NHS	Likely pathogenic	criteria provided, single submitter
3775474	NM_001291867.2(NHS):c.1928del (p.Ser643fs)	NHS	Likely pathogenic	criteria provided, single submitter
3899372	NM_001291867.2(NHS):c.906G>A (p.Trp302Ter)	NHS	Likely pathogenic	criteria provided, single submitter
3900608	NM_001291867.2(NHS):c.2012_2013insTAAAC (p.Ala672fs)	NHS	Likely pathogenic	criteria provided, single submitter
4531281	NM_001291867.2(NHS):c.1402del (p.Arg468fs)	NHS	Likely pathogenic	criteria provided, single submitter
167351	NM_001291867.2(NHS):c.152C>T (p.Ala51Val)	NHS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930367	NM_001291867.2(NHS):c.1228C>G (p.Gln410Glu)	NHS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
96638	NM_001291867.2(NHS):c.302_337dup (p.Glu101_Ala112dup)	NHS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030452	NM_001291867.2(NHS):c.546C>G (p.Asp182Glu)	NHS	Uncertain significance	criteria provided, multiple submitters, no conflicts
198926	NM_001291867.2(NHS):c.4783A>C (p.Thr1595Pro)	NHS	Uncertain significance	criteria provided, multiple submitters, no conflicts
211596	NM_001291867.2(NHS):c.176_177delinsAA (p.Arg59Gln)	NHS	Uncertain significance	criteria provided, multiple submitters, no conflicts
2574627	NM_001291867.2(NHS):c.566-52355A>G	NHS	Uncertain significance	criteria provided, single submitter
3598205	NM_001291867.2(NHS):c.1364T>C (p.Leu455Pro)	NHS	Uncertain significance	criteria provided, single submitter
198294	NM_001291867.2(NHS):c.3310C>T (p.His1104Tyr)	NHS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
96644	NM_001291867.2(NHS):c.566-10dup	NHS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NHS	Orphanet:627	Nance-Horan syndrome
NHS	Orphanet:98991	Early-onset nuclear cataract
NHS	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
NHS	HGNC:7820	ENSG00000188158	Q6T4R5	Actin remodeling regulator NHS	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NHS	Actin remodeling regulator NHS	May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation.

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)
NHS	Other/Unknown	no		NHS-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)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
endothelial cell	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NHS	214	ubiquitous	marker	oviduct epithelium, buccal mucosa cell, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NHS	970

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NHS	Q6T4R5	43.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
RAC2 GTPase cycle	1	126.9×	0.013	NHS
RAC3 GTPase cycle	1	119.0×	0.013	NHS
RAC1 GTPase cycle	1	61.1×	0.016	NHS

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 development in camera-type eye	1	374.5×	0.005	NHS
cell differentiation	1	29.1×	0.034	NHS

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
NHS	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	NHS

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)
NHS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.