Cataract 48

Summary

Cataract 48 (MONDO:0032735) is a disease caused by DNMBP (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: DNMBP (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 48
Mondo ID	MONDO:0032735
OMIM	618415
DOID	DOID:0070354
UMLS	C5193082
MedGen	1684457
GARD	0016350
Is cancer (heuristic)	no

Also known as: CTRCT48

Data availability: 11 ClinVar variants · 2 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 48

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 12 multiple types, cataract 34 multiple types, cataract 36, bhaskar jagannathan syndrome, autosomal dominant cataract, craniostenosis cataract, Kozlowski Rafinski Klicharska syndrome, cataract 49, 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

11 retrieved; paginated sample, class counts are floors:

6 benign, 3 pathogenic, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
626917	NM_015221.4(DNMBP):c.811C>T (p.Arg271Ter)	DNMBP	Pathogenic	criteria provided, single submitter
626918	NM_015221.4(DNMBP):c.2947_2948del (p.Glu982_Asp983insTer)	DNMBP	Pathogenic	no assertion criteria provided
626919	NM_015221.4(DNMBP):c.2852_2855del (p.Thr951fs)	DNMBP	Pathogenic	no assertion criteria provided
3148840	NM_015221.4(DNMBP):c.1442del (p.Gly481fs)	DNMBP	Likely pathogenic	criteria provided, single submitter
1699200	NM_015221.4(DNMBP):c.1232G>A (p.Gly411Asp)	DNMBP-AS1	Uncertain significance	criteria provided, single submitter
1255519	NM_015221.4(DNMBP):c.4320C>T (p.Ser1440=)	DNMBP	Benign	criteria provided, multiple submitters, no conflicts
1255520	NM_015221.4(DNMBP):c.4239T>G (p.Cys1413Trp)	DNMBP	Benign	criteria provided, multiple submitters, no conflicts
1255521	NM_015221.4(DNMBP):c.3744A>G (p.Pro1248=)	DNMBP	Benign	criteria provided, multiple submitters, no conflicts
1255522	NM_015221.4(DNMBP):c.3156+7A>G	DNMBP	Benign	criteria provided, multiple submitters, no conflicts
1255523	NM_015221.4(DNMBP):c.2883C>T (p.Asn961=)	DNMBP	Benign	criteria provided, multiple submitters, no conflicts
1255524	NM_015221.4(DNMBP):c.1332C>T (p.Pro444=)	DNMBP	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
DNMBP	Strong	Autosomal recessive	cataract 48	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNMBP	Orphanet:98994	Total early-onset 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
DNMBP	HGNC:30373	ENSG00000107554	Q6XZF7	Dynamin-binding protein	gencc,clinvar
DNMBP-AS1	HGNC:20431	ENSG00000227695		DNMBP antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNMBP	Dynamin-binding protein	Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton.

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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNMBP	Scaffold/PPI	no		DH_dom, GDS_CDC24_CS, SH3_domain
DNMBP-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic mucosa	1
ileal mucosa	1
jejunal mucosa	1
colonic epithelium	1
mucosa of transverse colon	1
olfactory segment of nasal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNMBP	279	ubiquitous	marker	jejunal mucosa, ileal mucosa, colonic mucosa
DNMBP-AS1	127	tissue_specific	marker	colonic epithelium, olfactory segment of nasal mucosa, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNMBP	1,328
DNMBP-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DNMBP	Q6XZF7	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
CDC42 GTPase cycle	1	72.3×	0.014	DNMBP

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
regulation of small GTPase mediated signal transduction	1	144.0×	0.016	DNMBP
regulation of cell shape	1	123.0×	0.016	DNMBP
cilium assembly	1	73.6×	0.018	DNMBP
intracellular signal transduction	1	38.1×	0.026	DNMBP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DNMBP	0	0
DNMBP-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
DNMBP	1	Binding:1

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	DNMBP, DNMBP-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)
DNMBP	1	—
DNMBP-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.