Cataract 11 multiple types

Summary

Cataract 11 multiple types (MONDO:0012527) is a disease caused by PITX3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: PITX3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 11 multiple types
Mondo ID	MONDO:0012527
MeSH	C535344
OMIM	610623
DOID	DOID:0110249
UMLS	C1864567
MedGen	351162
GARD	0010228
Is cancer (heuristic)	no

Also known as: cataract 11, multiple types · cataract 11, syndromic, autosomal recessive · CTRCT11 · early-onset non-syndromic cataract caused by mutation in PITX3 · PITX3 early-onset non-syndromic cataract · Posterior polar cataract, 4

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

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 11 multiple types

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 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

5 retrieved; paginated sample, class counts are floors:

1 benign, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
468353	NM_005029.4(PITX3):c.640_656dup (p.Gly220fs)	GBF1	Pathogenic	criteria provided, multiple submitters, no conflicts
468252	NM_005029.4(PITX3):c.640_656del (p.Ala214fs)	PITX3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6938	NM_005029.4(PITX3):c.38G>A (p.Ser13Asn)	GBF1	Likely pathogenic	criteria provided, single submitter
3340189	NM_005029.4(PITX3):c.669del (p.Leu225fs)	GBF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196404	NM_005029.4(PITX3):c.285C>T (p.Ile95=)	GBF1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
PITX3	Strong	Autosomal dominant	cataract 11 multiple types	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PITX3	Orphanet:162	Congenital cataract-anterior segment dysgenesis syndrome
PITX3	Orphanet:98993	Early-onset posterior polar 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
PITX3	HGNC:9006	ENSG00000107859	O75364	Pituitary homeobox 3	gencc,clinvar
GBF1	HGNC:4181	ENSG00000107862	Q92538	Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PITX3	Pituitary homeobox 3	Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development.
GBF1	Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1	Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of acti…

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PITX3	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf
GBF1	Other/Unknown	no		Sec7_dom, ARM-type_fold, Sec7_C_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
primordial germ cell in gonad	1
triceps brachii	1
adenohypophysis	1
colonic epithelium	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PITX3	64	tissue_specific	yes	hindlimb stylopod muscle, triceps brachii, primordial germ cell in gonad
GBF1	259	ubiquitous	marker	colonic epithelium, ventricular zone, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GBF1	2,436
PITX3	1,186

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GBF1	Q92538	71.42
PITX3	O75364	63.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 2 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
Assembly and Release of Dengue Virus Virions	1	1427.5×	0.004	GBF1
VxPx cargo-targeting to cilium	1	519.1×	0.006	GBF1
trans-Golgi Network Vesicle Budding	1	253.8×	0.008	GBF1
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.011	GBF1
COPI-mediated anterograde transport	1	109.8×	0.011	GBF1
Dengue Virus-Host Interactions	1	45.7×	0.022	GBF1

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
cell activation involved in immune response	1	8426.0×	0.001	GBF1
protein localization to endoplasmic reticulum tubular network	1	8426.0×	0.001	GBF1
negative regulation of gliogenesis	1	4213.0×	0.001	PITX3
establishment of monopolar cell polarity	1	4213.0×	0.001	GBF1
endoplasmic reticulum-Golgi intermediate compartment organization	1	4213.0×	0.001	GBF1
response to methamphetamine hydrochloride	1	4213.0×	0.001	PITX3
positive regulation of cell proliferation in midbrain	1	4213.0×	0.001	PITX3
cellular response to glial cell derived neurotrophic factor	1	4213.0×	0.001	PITX3
Golgi disassembly	1	1404.3×	0.003	GBF1
COPI coating of Golgi vesicle	1	1203.7×	0.003	GBF1
protein localization to endoplasmic reticulum exit site	1	1053.2×	0.004	GBF1
reactive oxygen species biosynthetic process	1	936.2×	0.004	GBF1
regulation of protein localization to cell surface	1	842.6×	0.004	GBF1
lens morphogenesis in camera-type eye	1	648.1×	0.005	PITX3
post-Golgi vesicle-mediated transport	1	526.6×	0.005	GBF1
Golgi to endosome transport	1	526.6×	0.005	GBF1
lens fiber cell differentiation	1	526.6×	0.005	PITX3
regulation of ARF protein signal transduction	1	443.5×	0.005	GBF1
protein localization to Golgi apparatus	1	401.2×	0.005	GBF1
response to immobilization stress	1	366.4×	0.006	PITX3
dopaminergic neuron differentiation	1	312.1×	0.006	PITX3
midbrain development	1	300.9×	0.006	PITX3
response to cocaine	1	290.6×	0.006	PITX3
lens development in camera-type eye	1	187.2×	0.009	PITX3
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	168.5×	0.010	GBF1
neutrophil chemotaxis	1	142.8×	0.011	GBF1
positive regulation of neuron apoptotic process	1	135.9×	0.011	PITX3
neuron development	1	127.7×	0.011	PITX3
regulation of mitotic cell cycle	1	120.4×	0.012	GBF1
retrograde transport, endosome to Golgi	1	102.8×	0.013	GBF1

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
PITX3	0	0
GBF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PITX3, GBF1

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)
PITX3	0	—
GBF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.