Cataract 12 multiple types

Summary

Cataract 12 multiple types (MONDO:0012701) is a disease caused by BFSP2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: BFSP2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 75

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 12 multiple types
Mondo ID	MONDO:0012701
MeSH	C566909
OMIM	611597
DOID	DOID:0110239
UMLS	C3808115
MedGen	814445
Is cancer (heuristic)	no

Also known as: cataract 12, multiple types · CTRCT12

Data availability: 75 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 › cataract 12 multiple types

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 18, 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

75 retrieved; paginated sample, class counts are floors:

37 uncertain significance, 16 benign, 10 likely benign, 6 conflicting classifications of pathogenicity, 4 benign/likely benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
646545	NM_003571.4(BFSP2):c.166del (p.Val56fs)	BFSP2	Pathogenic	criteria provided, single submitter
6584	NM_003571.4(BFSP2):c.694GAA[1] (p.Glu233del)	BFSP2	Pathogenic	criteria provided, multiple submitters, no conflicts
2315690	NM_003571.4(BFSP2):c.163G>A (p.Gly55Arg)	BFSP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343399	NM_003571.4(BFSP2):c.100T>C (p.Ser34Pro)	BFSP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
660770	NM_003571.4(BFSP2):c.1115C>T (p.Ala372Val)	BFSP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900456	NM_003571.4(BFSP2):c.370G>A (p.Ala124Thr)	BFSP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
902120	NM_003571.4(BFSP2):c.517C>T (p.Arg173Trp)	BFSP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
343412	NM_003571.4(BFSP2):c.865G>A (p.Glu289Lys)	BFSP2-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031336	NM_003571.4(BFSP2):c.13C>T (p.Arg5Ter)	BFSP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1442993	NM_003571.4(BFSP2):c.1058A>G (p.Lys353Arg)	BFSP2	Uncertain significance	criteria provided, single submitter
1513087	NM_003571.4(BFSP2):c.344TGG[1] (p.Val116del)	BFSP2	Uncertain significance	criteria provided, single submitter
2001969	NM_003571.4(BFSP2):c.1138G>A (p.Glu380Lys)	BFSP2	Uncertain significance	criteria provided, single submitter
2413884	NM_003571.4(BFSP2):c.190G>T (p.Gly64Trp)	BFSP2	Uncertain significance	criteria provided, single submitter
2439510	NM_003571.4(BFSP2):c.27C>G (p.Asp9Glu)	BFSP2	Uncertain significance	criteria provided, single submitter
2439511	NM_003571.4(BFSP2):c.461G>T (p.Arg154Leu)	BFSP2	Uncertain significance	criteria provided, single submitter
2530179	NM_003571.4(BFSP2):c.458T>A (p.Leu153Gln)	BFSP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2617661	NM_003571.4(BFSP2):c.130A>G (p.Thr44Ala)	BFSP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2715249	NM_003571.4(BFSP2):c.215G>A (p.Arg72His)	BFSP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2860615	NM_003571.4(BFSP2):c.185C>A (p.Pro62His)	BFSP2	Uncertain significance	criteria provided, single submitter
3220926	NM_003571.4(BFSP2):c.598_599insGGC (p.Lys200delinsArgGln)	BFSP2	Uncertain significance	criteria provided, single submitter
343397	NM_003571.4(BFSP2):c.5G>A (p.Ser2Asn)	BFSP2	Uncertain significance	criteria provided, single submitter
343407	NM_003571.4(BFSP2):c.422A>C (p.Glu141Ala)	BFSP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
343409	NM_003571.4(BFSP2):c.567A>G (p.Lys189=)	BFSP2	Uncertain significance	criteria provided, single submitter
343411	NM_003571.4(BFSP2):c.722A>G (p.Tyr241Cys)	BFSP2	Uncertain significance	criteria provided, single submitter
343416	NM_003571.4(BFSP2):c.*159T>G	BFSP2	Uncertain significance	criteria provided, single submitter
343418	NM_003571.4(BFSP2):c.*226C>A	BFSP2	Uncertain significance	criteria provided, single submitter
3480525	NM_003571.4(BFSP2):c.11G>A (p.Arg4Lys)	BFSP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
4292618	NM_003571.4(BFSP2):c.1213_1220delinsAGCAGAAGGA (p.Tyr405fs)	BFSP2	Uncertain significance	criteria provided, single submitter
4702069	NM_003571.4(BFSP2):c.899C>T (p.Ala300Val)	BFSP2	Uncertain significance	criteria provided, single submitter
4743599	NM_003571.4(BFSP2):c.973T>C (p.Ser325Pro)	BFSP2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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
BFSP2	Definitive	Autosomal dominant	cataract 12 multiple types	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BFSP2	Orphanet:441452	Early-onset lamellar cataract
BFSP2	Orphanet:98984	Pulverulent cataract
BFSP2	Orphanet:98985	Early-onset sutural cataract

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BFSP2	HGNC:1041	ENSG00000170819	Q13515	Phakinin	gencc,clinvar
BFSP2-AS1	HGNC:28425	ENSG00000249993		BFSP2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BFSP2	Phakinin	Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BFSP2	Other/Unknown	no		Keratin_I, IF_rod_dom
BFSP2-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

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
primordial germ cell in gonad	2
lens of camera-type eye	1
male germ line stem cell (sensu Vertebrata) in testis	1
bone marrow cell	1
cortical plate	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BFSP2	111	tissue_specific	yes	lens of camera-type eye, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
BFSP2-AS1	139	tissue_specific	yes	primordial germ cell in gonad, bone marrow cell, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BFSP2	1,203
BFSP2-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BFSP2	Q13515	78.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
lens fiber cell development	1	2106.5×	0.002	BFSP2
cell maturation	1	443.5×	0.005	BFSP2
intermediate filament organization	1	240.7×	0.006	BFSP2
visual perception	1	79.5×	0.013	BFSP2

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
BFSP2	0	0
BFSP2-AS1	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	2	BFSP2, BFSP2-AS1

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)
BFSP2	0	—
BFSP2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.