cataract 13 with adult I phenotype

Summary

cataract 13 with adult I phenotype (MONDO:0007289) is a disease caused by GCNT2 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: GCNT2 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 47

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 13 with adult I phenotype
Mondo ID	MONDO:0007289
OMIM	116700
DOID	DOID:0110242
UMLS	C3805373
MedGen	811703
GARD	0024546
Is cancer (heuristic)	no

Also known as: cataract 13 with adult I phenotype · CTRCT13

Data availability: 47 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 13 with adult I phenotype

Related subtypes (28): cataract 32 multiple types, cataract 8 multiple types, cataract 42, cataract 20 multiple types, cataract 6 multiple types, 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, 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

47 retrieved; paginated sample, class counts are floors:

17 uncertain significance, 10 pathogenic, 7 benign, 5 likely benign, 3 conflicting classifications of pathogenicity, 2 benign/likely benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065633	NM_145649.5(GCNT2):c.14G>A (p.Trp5Ter)	GCNT2	Pathogenic	criteria provided, single submitter
1437805	NM_145649.5(GCNT2):c.1000A>T (p.Arg334Ter)	GCNT2	Pathogenic	criteria provided, single submitter
2424190	NC_000006.11:g.(?10556657)(10626840_?)del	GCNT2	Pathogenic	criteria provided, single submitter
2918140	NM_001491.3(GCNT2):c.760del (p.His254fs)	GCNT2	Pathogenic	criteria provided, single submitter
571035	NM_001491.3(GCNT2):c.60del (p.Ile20fs)	GCNT2	Pathogenic	criteria provided, single submitter
571381	NM_001491.3(GCNT2):c.710_711insT (p.Lys237fs)	GCNT2	Pathogenic	criteria provided, single submitter
830705	NC_000006.12:g.(?10528892)(10557362_?)del	GCNT2	Pathogenic	criteria provided, single submitter
830756	NC_000006.12:g.(?10556404)(10626627_?)del	GCNT2	Pathogenic	criteria provided, single submitter
844536	NM_145649.5(GCNT2):c.1046A>G (p.Tyr349Cys)	GCNT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
9128	NM_145649.5(GCNT2):c.1049G>A (p.Gly350Glu)	GCNT2	Pathogenic	criteria provided, single submitter
9130	NM_001491.2(GCNT2):c.-117_*41del	GCNT2	Pathogenic	no assertion criteria provided
4849340	NM_145649.5(GCNT2):c.651dup (p.Gly218fs)	GCNT2	Likely pathogenic	criteria provided, single submitter
4849446	NM_001491.3(GCNT2):c.707_708dup (p.Lys237fs)	GCNT2	Likely pathogenic	criteria provided, single submitter
354701	NM_001491.3(GCNT2):c.254C>G (p.Pro85Arg)	GCNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
391563	NM_145649.5(GCNT2):c.1018G>A (p.Gly340Ser)	GCNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
9129	NM_145649.5(GCNT2):c.1154G>A (p.Arg385His)	GCNT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1421288	NC_000006.11:g.(?10398650)(10882026_?)dup	C6orf52	Uncertain significance	criteria provided, single submitter
1020672	NM_001491.3(GCNT2):c.722A>G (p.Tyr241Cys)	GCNT2	Uncertain significance	criteria provided, single submitter
1492800	NM_001491.3(GCNT2):c.403A>G (p.Lys135Glu)	GCNT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1499083	NM_001491.3(GCNT2):c.96C>G (p.Ser32Arg)	GCNT2	Uncertain significance	criteria provided, single submitter
1683746	NM_145649.5(GCNT2):c.558T>G (p.Tyr186Ter)	GCNT2	Uncertain significance	criteria provided, single submitter
1905602	NM_001491.3(GCNT2):c.671T>C (p.Ile224Thr)	GCNT2	Uncertain significance	criteria provided, single submitter
191204	NM_145649.5(GCNT2):c.1025A>G (p.Tyr342Cys)	GCNT2	Uncertain significance	criteria provided, single submitter
2054627	NM_001491.3(GCNT2):c.572A>G (p.Gln191Arg)	GCNT2	Uncertain significance	criteria provided, single submitter
225372	NM_001491.3(GCNT2):c.259_262del (p.Ser87fs)	GCNT2	Uncertain significance	criteria provided, single submitter
2359197	NM_145649.5(GCNT2):c.694G>A (p.Val232Ile)	GCNT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2867950	NM_145649.5(GCNT2):c.1121C>T (p.Pro374Leu)	GCNT2	Uncertain significance	criteria provided, single submitter
3893104	NM_145649.5(GCNT2):c.926-35241G>A	GCNT2	Uncertain significance	criteria provided, single submitter
3893105	NM_145649.5(GCNT2):c.149A>T (p.His50Leu)	GCNT2	Uncertain significance	criteria provided, single submitter
3893106	NM_145649.5(GCNT2):c.926-34886_926-34885del	GCNT2	Uncertain significance	criteria provided, single submitter

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
GCNT2	Definitive	Autosomal recessive	cataract 13 with adult I phenotype	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GCNT2	Orphanet:98994	Total early-onset cataract

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GCNT2	HGNC:4204	ENSG00000111846	Q8N0V5	N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase	gencc,clinvar
C6orf52	HGNC:20881	ENSG00000137434	Q5T4I8	Putative uncharacterized protein C6orf52	clinvar
HPCAL1	HGNC:5145	ENSG00000115756	P37235	Hippocalcin-like protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GCNT2	N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase	Branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans.
HPCAL1	Hippocalcin-like protein 1	May be involved in the calcium-dependent regulation of rhodopsin phosphorylation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GCNT2	Enzyme (other)	yes	2.4.1.150	Glyco_trans_14
C6orf52	Other/Unknown	no		TSAP1, TSAP1_C
HPCAL1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
heart left ventricle	1
primordial germ cell in gonad	1
right testis	1
testis	1
cerebellar cortex	1
cerebellar vermis	1
cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GCNT2	136	ubiquitous	marker	primordial germ cell in gonad, heart left ventricle, male germ line stem cell (sensu Vertebrata) in testis
C6orf52	132	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, testis
HPCAL1	289	ubiquitous	marker	cerebellar vermis, cerebellum, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HPCAL1	2,565
C6orf52	1,219
GCNT2	910

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HPCAL1	P37235	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GCNT2	Q8N0V5	91.66
C6orf52	Q5T4I8	58.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
multicellular organism development	1	4213.0×	0.003	GCNT2
maintenance of lens transparency	1	1053.2×	0.007	GCNT2
positive regulation of heterotypic cell-cell adhesion	1	648.1×	0.007	GCNT2
negative regulation of cell-substrate adhesion	1	526.6×	0.007	GCNT2
glycosaminoglycan biosynthetic process	1	421.3×	0.007	GCNT2
post-transcriptional regulation of gene expression	1	324.1×	0.007	GCNT2
glycoprotein biosynthetic process	1	168.5×	0.011	GCNT2
positive regulation of epithelial to mesenchymal transition	1	159.0×	0.011	GCNT2
regulation of signal transduction	1	133.8×	0.012	HPCAL1
transforming growth factor beta receptor signaling pathway	1	79.5×	0.018	GCNT2
positive regulation of ERK1 and ERK2 cascade	1	42.6×	0.030	GCNT2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	39.2×	0.030	GCNT2
positive regulation of cell migration	1	30.9×	0.035	GCNT2
positive regulation of cell population proliferation	1	16.8×	0.059	GCNT2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GCNT2	0	0
C6orf52	0	0
HPCAL1	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
HPCAL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GCNT2	2.4.1.150	N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	GCNT2
E	Difficult family or no structure, no drug	2	C6orf52, HPCAL1

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GCNT2	0	—
C6orf52	0	—
HPCAL1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.