Cataract 38

Summary

Cataract 38 (MONDO:0013859) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 283

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 38
Mondo ID	MONDO:0013859
OMIM	614691
DOID	DOID:0110245
UMLS	C3553494
MedGen	766408
GARD	0024957
Is cancer (heuristic)	no

Also known as: AGK early-onset non-syndromic cataract · cataract 38 · cataract 38, autosomal recessive · cataract type 38 · CATC5 · CTRCT38 · early-onset non-syndromic cataract caused by mutation in AGK

Data availability: 283 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 38

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 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

283 retrieved; paginated sample, class counts are floors:

117 likely benign, 91 uncertain significance, 24 conflicting classifications of pathogenicity, 20 pathogenic, 10 benign/likely benign, 9 benign, 8 likely pathogenic, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070308	NM_018238.4(AGK):c.1035dup (p.Ile346fs)	AGK	Pathogenic	criteria provided, single submitter
1351396	NM_018238.4(AGK):c.412C>T (p.Arg138Ter)	AGK	Pathogenic	criteria provided, multiple submitters, no conflicts
1415657	NM_018238.4(AGK):c.632G>A (p.Trp211Ter)	AGK	Pathogenic	criteria provided, single submitter
1456624	NC_000007.13:g.(?141255267)(141301100_?)del	AGK	Pathogenic	criteria provided, single submitter
2021455	NM_018238.4(AGK):c.1166_1167dup (p.Tyr390fs)	AGK	Pathogenic	criteria provided, single submitter
209129	NM_018238.4(AGK):c.424-3C>G	AGK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
209130	NM_018238.4(AGK):c.409C>T (p.Arg137Ter)	AGK	Pathogenic	criteria provided, multiple submitters, no conflicts
2120043	NM_018238.4(AGK):c.860G>A (p.Trp287Ter)	AGK	Pathogenic	criteria provided, single submitter
2426458	NC_000007.13:g.(?141292926)(141293005_?)del	AGK	Pathogenic	criteria provided, single submitter
280255	NM_018238.4(AGK):c.1047-2A>T	AGK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2921399	NM_018238.4(AGK):c.356dup (p.Ile120fs)	AGK	Pathogenic	criteria provided, single submitter
2931348	NM_018238.4(AGK):c.25C>T (p.Arg9Ter)	AGK	Pathogenic	criteria provided, single submitter
2947480	NM_018238.4(AGK):c.388G>T (p.Glu130Ter)	AGK	Pathogenic	criteria provided, single submitter
2952828	NM_018238.4(AGK):c.409del (p.Arg137fs)	AGK	Pathogenic	criteria provided, single submitter
30829	NM_018238.4(AGK):c.841C>T (p.Arg281Ter)	AGK	Pathogenic	criteria provided, multiple submitters, no conflicts
3245750	NC_000007.13:g.(?140434397)(141759786_?)del	AGK	Pathogenic	criteria provided, single submitter
3245751	NC_000007.13:g.(?141351305)(141352724_?)del	AGK	Pathogenic	criteria provided, single submitter
3756552	NM_018238.4(AGK):c.269T>G (p.Leu90Ter)	AGK	Pathogenic	criteria provided, single submitter
429694	NM_018238.4(AGK):c.297+2T>C	AGK	Pathogenic	criteria provided, multiple submitters, no conflicts
4845888	NM_018238.4(AGK):c.1046_1046+1dup	AGK	Pathogenic	criteria provided, single submitter
524160	NM_018238.4(AGK):c.1141_1142dup (p.Ser382fs)	AGK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
871496	NM_018238.4(AGK):c.672C>A (p.Tyr224Ter)	AGK	Pathogenic	criteria provided, multiple submitters, no conflicts
873475	NM_018238.4(AGK):c.523_524del (p.Ile175fs)	AGK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
987518	NM_018238.4(AGK):c.1131+2T>C	AGK	Pathogenic	criteria provided, single submitter
2021993	NM_018238.4(AGK):c.519-2A>G	AGK	Likely pathogenic	criteria provided, single submitter
2135115	NM_018238.4(AGK):c.519-1G>A	AGK	Likely pathogenic	criteria provided, single submitter
2163165	NM_018238.4(AGK):c.1150_1154del (p.Phe383_Ser384insTer)	AGK	Likely pathogenic	criteria provided, single submitter
2426460	NC_000007.13:g.(?141292926)(141293005_?)dup	AGK	Likely pathogenic	criteria provided, single submitter
3756798	NM_018238.4(AGK):c.976-1G>C	AGK	Likely pathogenic	criteria provided, single submitter
3762105	NM_018238.4(AGK):c.222-2A>C	AGK	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
AGK	Supportive	Autosomal dominant	total early-onset cataract	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AGK	Orphanet:1369	Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome
AGK	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
AGK	HGNC:21869	ENSG00000006530	Q53H12	Acylglycerol kinase, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AGK	Acylglycerol kinase, mitochondrial	Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AGK	Kinase	yes	2.7.1.94	Diacylglycerol_kinase_cat_dom, NAD/diacylglycerol_kinase_sf, ATP-NAD_kinase_N

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
adrenal tissue	1
cerebellar cortex	1
cerebellar hemisphere	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AGK	161	ubiquitous	marker	adrenal tissue, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AGK	2,341

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AGK	Q53H12	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Glycerophospholipid biosynthesis	1	335.9×	0.012	AGK
Oncogenic MAPK signaling	1	248.3×	0.012	AGK
Phospholipid metabolism	1	200.3×	0.012	AGK
Signaling by BRAF and RAF1 fusions	1	170.4×	0.012	AGK
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.028	AGK
Metabolism of lipids	1	31.6×	0.042	AGK
Disease	1	13.1×	0.086	AGK
Metabolism	1	11.6×	0.086	AGK

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
glycerolipid metabolic process	1	2106.5×	0.001	AGK
lipid phosphorylation	1	1685.2×	0.001	AGK
protein insertion into mitochondrial inner membrane	1	1296.3×	0.001	AGK
sphingosine biosynthetic process	1	1053.2×	0.001	AGK
ceramide biosynthetic process	1	421.3×	0.002	AGK

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
AGK	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
AGK	19	Binding:19

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AGK	2.7.1.94	acylglycerol kinase

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	AGK
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)
AGK	19	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.