Cataract 45

Summary

Cataract 45 (MONDO:0014799) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 45
Mondo ID	MONDO:0014799
OMIM	616851
DOID	DOID:0110262
UMLS	C4225182
MedGen	895198
GARD	0025016
Is cancer (heuristic)	no

Also known as: cataract 45 · cataract type 45 · CTRCT45 · early-onset non-syndromic cataract caused by mutation in SIPA1L3 · SIPA1L3 early-onset non-syndromic cataract

Data availability: 12 ClinVar variants · 5 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 45

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 44, 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

12 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 2 benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1687350	NM_015073.3(SIPA1L3):c.3492dup (p.Gly1165fs)	SIPA1L3	Pathogenic	criteria provided, single submitter
223242	NM_015073.3(SIPA1L3):c.4489C>T (p.Arg1497Ter)	SIPA1L3	Pathogenic	no assertion criteria provided
1032651	NM_015073.3(SIPA1L3):c.947G>A (p.Arg316His)	SIPA1L3	Uncertain significance	criteria provided, single submitter
1360785	NM_015073.3(SIPA1L3):c.4808C>G (p.Pro1603Arg)	SIPA1L3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382071	NM_015073.3(SIPA1L3):c.2705T>C (p.Leu902Ser)	SIPA1L3	Uncertain significance	criteria provided, single submitter
3382117	NM_015073.3(SIPA1L3):c.727C>T (p.Arg243Trp)	SIPA1L3	Uncertain significance	criteria provided, single submitter
3775329	NM_015073.3(SIPA1L3):c.2029+4A>C	SIPA1L3	Uncertain significance	criteria provided, single submitter
3780603	NM_015073.3(SIPA1L3):c.5275G>T (p.Glu1759Ter)	SIPA1L3	Uncertain significance	criteria provided, single submitter
931642	NM_015073.3(SIPA1L3):c.3535T>G (p.Tyr1179Asp)	SIPA1L3	Uncertain significance	criteria provided, single submitter
931643	NM_015073.3(SIPA1L3):c.5248C>T (p.Arg1750Trp)	SIPA1L3	Uncertain significance	criteria provided, single submitter
1251838	NM_015073.3(SIPA1L3):c.5203-23T>C	SIPA1L3	Benign	criteria provided, multiple submitters, no conflicts
1273720	NM_015073.3(SIPA1L3):c.5203-29G>A	SIPA1L3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
SIPA1L3	Moderate	Autosomal dominant	cataract 45	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SIPA1L3	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
SIPA1L3	HGNC:23801	ENSG00000105738	O60292	Signal-induced proliferation-associated 1-like protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SIPA1L3	Signal-induced proliferation-associated 1-like protein 3	Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SIPA1L3	Scaffold/PPI	no		Rap/Ran_GAP_dom, PDZ, SIPA1L_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
buccal mucosa cell	1
endometrium epithelium	1
islet of Langerhans	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SIPA1L3	257	ubiquitous	marker	buccal mucosa cell, endometrium epithelium, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SIPA1L3	1,149

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SIPA1L3	O60292	56.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
establishment of epithelial cell polarity	1	1203.7×	0.003	SIPA1L3
epithelial cell morphogenesis	1	936.2×	0.003	SIPA1L3
eye development	1	351.1×	0.006	SIPA1L3
hematopoietic progenitor cell differentiation	1	237.3×	0.006	SIPA1L3
regulation of small GTPase mediated signal transduction	1	144.0×	0.008	SIPA1L3
cytoskeleton organization	1	132.7×	0.008	SIPA1L3

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
SIPA1L3	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	SIPA1L3

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)
SIPA1L3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.