Cataract 44

Summary

Cataract 44 (MONDO:0014673) is a disease caused by LSS (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LSS (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 44
Mondo ID	MONDO:0014673
OMIM	616509
DOID	DOID:0110267
UMLS	C4225300
MedGen	907487
GARD	0016127
Is cancer (heuristic)	no

Also known as: cataract 44 · cataract type 44 · CTRCT44 · early-onset non-syndromic cataract caused by mutation in LSS · LSS early-onset non-syndromic cataract · total early-onset cataract

Data availability: 18 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 44

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 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 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

18 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 5 benign, 2 benign/likely benign, 2 pathogenic, 2 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1526304	NM_002340.6(LSS):c.530G>A (p.Arg177Gln)	LSS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
221227	NM_002340.6(LSS):c.1741T>C (p.Trp581Arg)	LSS	Pathogenic	no assertion criteria provided
599317	NM_002340.6(LSS):c.1025T>G (p.Ile342Ser)	LSS	Pathogenic	no assertion criteria provided
3065729	NM_002340.6(LSS):c.1317+1G>T	LSS	Likely pathogenic	criteria provided, single submitter
599319	NM_002340.6(LSS):c.1172T>C (p.Phe391Ser)	LSS	Likely pathogenic	criteria provided, single submitter
221226	NM_002340.6(LSS):c.1762G>A (p.Gly588Ser)	LSS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028406	NM_002340.6(LSS):c.1228T>C (p.Cys410Arg)	LSS	Uncertain significance	criteria provided, single submitter
1033157	NM_002340.6(LSS):c.347G>A (p.Arg116His)	LSS	Uncertain significance	criteria provided, single submitter
2046152	NM_002340.6(LSS):c.1564G>A (p.Gly522Arg)	LSS	Uncertain significance	criteria provided, multiple submitters, no conflicts
3393305	NM_002340.6(LSS):c.1949A>G (p.His650Arg)	LSS	Uncertain significance	criteria provided, single submitter
599318	NM_002340.6(LSS):c.1887G>T (p.Trp629Cys)	LSS	Uncertain significance	criteria provided, single submitter
1201735	NM_002340.6(LSS):c.181-27dup	LSS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1287852	NM_002340.6(LSS):c.181-16_181-15del	LSS	Benign	criteria provided, multiple submitters, no conflicts
677172	NM_002340.6(LSS):c.551-6G>C	LSS	Benign	criteria provided, multiple submitters, no conflicts
677173	NM_002340.6(LSS):c.784-6C>T	LSS	Benign	criteria provided, multiple submitters, no conflicts
677174	NM_002340.6(LSS):c.864G>C (p.Pro288=)	LSS	Benign	criteria provided, multiple submitters, no conflicts
677175	NM_002340.6(LSS):c.1924T>G (p.Leu642Val)	LSS	Benign	criteria provided, multiple submitters, no conflicts
783885	NM_002340.6(LSS):c.752C>T (p.Ala251Val)	LSS	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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
LSS	Strong	Autosomal recessive	cataract 44	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LSS	Orphanet:1366	Autosomal recessive palmoplantar keratoderma and congenital alopecia
LSS	Orphanet:2850	Alopecia-intellectual disability syndrome
LSS	Orphanet:55654	Hypotrichosis simplex
LSS	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
LSS	HGNC:6708	ENSG00000160285	P48449	Lanosterol synthase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LSS	Lanosterol synthase	Key enzyme in the cholesterol biosynthesis pathway.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LSS	Enzyme (other)	yes	5.4.99.7	Terpene_synthase_CS, Terpenoid_cyclase/PrenylTrfase, Squalene_cyclase

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
C1 segment of cervical spinal cord	1
mucosa of stomach	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LSS	134	ubiquitous	marker	mucosa of stomach, C1 segment of cervical spinal cord, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LSS	1,562

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LSS	P48449	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Cholesterol biosynthesis	1	1142.0×	0.005	LSS
Lanosterol biosynthesis	1	761.3×	0.005	LSS
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	317.2×	0.007	LSS
Activation of gene expression by SREBF (SREBP)	1	259.6×	0.007	LSS
Metabolism of steroids	1	137.6×	0.010	LSS
Metabolism of lipids	1	31.6×	0.037	LSS
Metabolism	1	11.6×	0.086	LSS

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
triterpenoid biosynthetic process	1	16852.0×	2e-04	LSS
steroid biosynthetic process	1	601.9×	0.003	LSS
cholesterol biosynthetic process	1	421.3×	0.003	LSS
regulation of protein stability	1	125.8×	0.008	LSS

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LSS	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
LSS	46	Binding:45, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LSS	5.4.99.7	Lanosterol synthase

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	1	LSS
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
LSS	46	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.