Cataract 18

Summary

Cataract 18 (MONDO:0012395) is a disease caused by FYCO1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: FYCO1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 311

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 18
Mondo ID	MONDO:0012395
MeSH	C535337
OMIM	610019
DOID	DOID:0110238
UMLS	C1864908
MedGen	351249
GARD	0009892
Is cancer (heuristic)	no

Also known as: cataract (disease) caused by mutation in FYCO1 · cataract 18 · cataract 18, autosomal recessive · cataract type 18 · CATC2 · CTRCT18 · FYCO1 cataract (disease)

Data availability: 311 ClinVar variants · 3 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 › cataract 18

Related subtypes (28): immature cataract, diabetic cataract, mature cataract, tetanic cataract, myotonic cataract, senile cataract, diabetes mellitus type 2 associated cataract, cataract 4 multiple types, cataract 29, cataract 1 multiple types, early-onset non-syndromic cataract, cataract 3 multiple types, cataract 9 multiple types, cataract 28, cataract 12 multiple types, cataract 34 multiple types, cataract 36, bhaskar jagannathan syndrome, autosomal dominant cataract, craniostenosis cataract, Kozlowski Rafinski Klicharska syndrome, cataract 49, cataract 48, hypermature cataract, nuclear cataract, cortical cataract, cataract 2, multiple types, cataract 50 with or without glaucoma

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

311 retrieved; paginated sample, class counts are floors:

143 uncertain significance, 56 benign, 44 likely benign, 25 conflicting classifications of pathogenicity, 23 pathogenic, 14 benign/likely benign, 5 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1180699	NM_024513.4(FYCO1):c.3330C>A (p.Cys1110Ter)	FYCO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322945	NM_024513.4(FYCO1):c.524G>A (p.Trp175Ter)	FYCO1	Pathogenic	criteria provided, single submitter
1386641	NM_024513.4(FYCO1):c.3861del (p.Glu1287fs)	FYCO1	Pathogenic	criteria provided, single submitter
1430203	NM_024513.4(FYCO1):c.528_529insGGCAAAGT (p.Thr177fs)	FYCO1	Pathogenic	criteria provided, single submitter
1443310	NM_024513.4(FYCO1):c.575G>A (p.Trp192Ter)	FYCO1	Pathogenic	criteria provided, single submitter
1447466	NM_024513.4(FYCO1):c.3161del (p.Ala1054fs)	FYCO1	Pathogenic	criteria provided, single submitter
1457244	NM_024513.4(FYCO1):c.3322A>T (p.Lys1108Ter)	FYCO1	Pathogenic	criteria provided, single submitter
1709262	NM_024513.4(FYCO1):c.265_267delinsTGA (p.Arg89Ter)	FYCO1	Pathogenic	criteria provided, multiple submitters, no conflicts
2203348	NM_024513.4(FYCO1):c.2345del (p.Gln782fs)	FYCO1	Pathogenic	criteria provided, single submitter
30645	NM_024513.4(FYCO1):c.1045C>T (p.Gln349Ter)	FYCO1	Pathogenic	no assertion criteria provided
30646	NM_024513.4(FYCO1):c.2206C>T (p.Gln736Ter)	FYCO1	Pathogenic	no assertion criteria provided
30648	NM_024513.4(FYCO1):c.3858_3862dup (p.Leu1288fs)	FYCO1	Pathogenic	no assertion criteria provided
30649	NM_024513.4(FYCO1):c.4127T>C (p.Leu1376Pro)	FYCO1	Pathogenic	no assertion criteria provided
30650	NM_024513.4(FYCO1):c.1546C>T (p.Gln516Ter)	FYCO1	Pathogenic	no assertion criteria provided
3359081	NM_024513.4(FYCO1):c.2386C>T (p.Gln796Ter)	FYCO1	Pathogenic	criteria provided, single submitter
3665660	NM_024513.4(FYCO1):c.2483_2487dup (p.Leu830fs)	FYCO1	Pathogenic	criteria provided, single submitter
3694827	NM_024513.4(FYCO1):c.1410G>A (p.Trp470Ter)	FYCO1	Pathogenic	criteria provided, single submitter
3726918	NM_024513.4(FYCO1):c.2308del (p.Gln770fs)	FYCO1	Pathogenic	criteria provided, single submitter
3778776	NM_024513.4(FYCO1):c.402G>A (p.Trp134Ter)	FYCO1	Pathogenic	criteria provided, single submitter
4293908	NM_024513.4(FYCO1):c.3412G>T (p.Glu1138Ter)	FYCO1	Pathogenic	criteria provided, single submitter
430962	NM_024513.4(FYCO1):c.3327_3328del (p.Cys1110fs)	FYCO1	Pathogenic	criteria provided, multiple submitters, no conflicts
4747891	NM_024513.4(FYCO1):c.1327del (p.Ala443fs)	FYCO1	Pathogenic	criteria provided, single submitter
660217	NM_024513.4(FYCO1):c.2505del (p.Ala836fs)	FYCO1	Pathogenic	criteria provided, single submitter
982778	NM_024513.4(FYCO1):c.1411C>T (p.Arg471Ter)	FYCO1	Pathogenic	criteria provided, single submitter
2500891	NM_024513.4(FYCO1):c.3456G>A (p.Trp1152Ter)	FYCO1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3683796	NM_024513.4(FYCO1):c.3269+1G>C	FYCO1	Likely pathogenic	criteria provided, single submitter
503725	NM_024513.4(FYCO1):c.3150+1G>T	FYCO1	Likely pathogenic	criteria provided, single submitter
693984	NM_024513.4(FYCO1):c.1621C>T (p.Gln541Ter)	FYCO1	Likely pathogenic	criteria provided, single submitter
982651	NM_024513.4(FYCO1):c.793dup (p.Ala265fs)	FYCO1	Likely pathogenic	criteria provided, single submitter
1978744	NM_024513.4(FYCO1):c.3425T>C (p.Ile1142Thr)	FYCO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
FYCO1	Definitive	Autosomal recessive	cataract 18	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FYCO1	Orphanet:98991	Early-onset nuclear cataract
FYCO1	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
FYCO1	HGNC:14673	ENSG00000163820	Q9BQS8	FYVE and coiled-coil domain-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FYCO1	FYVE and coiled-coil domain-containing protein 1	May mediate microtubule plus end-directed vesicle transport.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FYCO1	Transcription factor	no		Znf_FYVE, Run_dom, GOLD_dom

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
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FYCO1	284	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FYCO1	1,637

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FYCO1	Q9BQS8	3

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
plus-end-directed vesicle transport along microtubule	1	2808.7×	4e-04	FYCO1
positive regulation of autophagosome maturation	1	2407.4×	4e-04	FYCO1

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
FYCO1	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	FYCO1

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)
FYCO1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.