Cataract 21 multiple types

Summary

Cataract 21 multiple types (MONDO:0012437) is a disease caused by MAF (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: MAF (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 93

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataract 21 multiple types
Mondo ID	MONDO:0012437
MeSH	C565703
OMIM	610202
DOID	DOID:0110256
UMLS	C1857768
MedGen	347538
GARD	0024866
Is cancer (heuristic)	no

Also known as: cataract 21, multiple types · CTRCT21 · early-onset non-syndromic cataract caused by mutation in MAF · MAF early-onset non-syndromic cataract

Data availability: 93 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 › early-onset non-syndromic cataract › cataract 21 multiple types

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 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

93 retrieved; paginated sample, class counts are floors:

28 likely benign, 28 uncertain significance, 8 benign/likely benign, 8 benign, 7 pathogenic, 6 likely pathogenic, 5 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
655227	NC_000016.10:g.(?78278583)(80589366_?)del	DYNLRB2	Pathogenic	criteria provided, single submitter
13231	NM_005360.5(MAF):c.863G>C (p.Arg288Pro)	MAF	Pathogenic	no assertion criteria provided
13232	NM_005360.5(MAF):c.890A>G (p.Lys297Arg)	MAF	Pathogenic	no assertion criteria provided
1360617	NM_005360.5(MAF):c.895C>T (p.Arg299Cys)	MAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
474940	NM_005360.5(MAF):c.905C>T (p.Ala302Val)	MAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4784054	NM_005360.5(MAF):c.-7_701del (p.Met1_Gly234del)	MAF	Pathogenic	criteria provided, single submitter
541764	NM_005360.5(MAF):c.295_312delinsTGCA (p.Gln99fs)	MAF	Pathogenic	criteria provided, single submitter
664291	NM_005360.5(MAF):c.881G>A (p.Arg294Gln)	MAF	Pathogenic	criteria provided, single submitter
830955	NC_000016.10:g.(?79594440)(79599922_?)del	MAF	Pathogenic	criteria provided, single submitter
952303	NM_005360.5(MAF):c.916C>G (p.Arg306Gly)	MAF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320073	NM_005360.5(MAF):c.185C>T (p.Thr62Met)	MAF	Likely pathogenic	criteria provided, multiple submitters, no conflicts
190235	NM_005360.5(MAF):c.895C>A (p.Arg299Ser)	MAF	Likely pathogenic	criteria provided, single submitter
190236	NM_005360.5(MAF):c.908A>C (p.Gln303Pro)	MAF	Likely pathogenic	criteria provided, single submitter
2574628	NM_005360.5(MAF):c.871C>G (p.Gln291Glu)	MAF	Likely pathogenic	criteria provided, single submitter
2628089	NM_005360.5(MAF):c.206del (p.Pro69fs)	MAF	Likely pathogenic	criteria provided, single submitter
932083	NM_005360.5(MAF):c.941A>C (p.His314Pro)	MAF	Likely pathogenic	criteria provided, single submitter
1144321	NM_005360.5(MAF):c.678CGG[7] (p.Gly238del)	MAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1313952	NM_005360.5(MAF):c.460G>A (p.Gly154Ser)	MAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1350488	NM_005360.5(MAF):c.678CGG[9] (p.Gly238dup)	MAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1699336	NM_005360.5(MAF):c.412C>A (p.Leu138Met)	MAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2672655	NM_005360.5(MAF):c.695G>T (p.Gly232Val)	MAF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1470812	NM_005360.5(MAF):c.797T>G (p.Leu266Arg)	MAF	Uncertain significance	criteria provided, single submitter
1709635	NM_005360.5(MAF):c.899G>A (p.Gly300Asp)	MAF	Uncertain significance	criteria provided, single submitter
1721911	NM_005360.5(MAF):c.922A>G (p.Lys308Glu)	MAF	Uncertain significance	criteria provided, single submitter
2000538	NM_005360.5(MAF):c.902A>G (p.Tyr301Cys)	MAF	Uncertain significance	criteria provided, single submitter
2001513	NM_005360.5(MAF):c.866T>A (p.Leu289Gln)	MAF	Uncertain significance	criteria provided, single submitter
2063482	NM_005360.5(MAF):c.655G>A (p.Gly219Ser)	MAF	Uncertain significance	criteria provided, single submitter
2064881	NM_005360.5(MAF):c.468G>C (p.Glu156Asp)	MAF	Uncertain significance	criteria provided, single submitter
2093066	NM_005360.5(MAF):c.935A>G (p.Gln312Arg)	MAF	Uncertain significance	criteria provided, single submitter
2141242	NM_005360.5(MAF):c.644G>A (p.Gly215Asp)	MAF	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 4 · 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
MAF	Definitive	Autosomal dominant	cataract 21 multiple types	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAF	Orphanet:1272	Aymé-Gripp syndrome
MAF	Orphanet:1377	Cataract-microcornea syndrome
MAF	Orphanet:98984	Pulverulent cataract
MAF	Orphanet:98989	Cerulean cataract

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MAF	HGNC:6776	ENSG00000178573	O75444	Transcription factor Maf	gencc,clinvar
DYNLRB2	HGNC:15467	ENSG00000168589	Q8TF09	Dynein light chain roadblock-type 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAF	Transcription factor Maf	Acts as a transcriptional activator or repressor.
DYNLRB2	Dynein light chain roadblock-type 2	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function.

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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAF	Transcription factor	no		bZIP_Maf, bZIP, TF_DNA-bd_sf
DYNLRB2	Other/Unknown	no		Roadblock/LAMTOR2_dom, DYNLRB1/2

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
germinal epithelium of ovary	1
gingiva	1
jejunal mucosa	1
bronchial epithelial cell	1
bronchus	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAF	290	ubiquitous	marker	jejunal mucosa, germinal epithelium of ovary, gingiva
DYNLRB2	182	broad	marker	bronchial epithelial cell, right uterine tube, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAF	4,111
DYNLRB2	1,444

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYNLRB2	Q8TF09	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAF	O75444	62.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX2 regulates bone development	1	407.9×	0.017	MAF
RUNX2 regulates osteoblast differentiation	1	228.4×	0.017	MAF
Transcriptional regulation by RUNX2	1	126.9×	0.020	MAF
Intraflagellar transport	1	100.2×	0.020	DYNLRB2
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	73.2×	0.022	MAF
RNA Polymerase II Transcription	1	11.3×	0.116	MAF
Gene expression (Transcription)	1	8.9×	0.125	MAF
Generic Transcription Pathway	1	7.5×	0.128	MAF

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
regulation of chondrocyte differentiation	1	702.2×	0.008	MAF
megakaryocyte differentiation	1	601.9×	0.008	MAF
lens fiber cell differentiation	1	526.6×	0.008	MAF
integrated stress response signaling	1	351.1×	0.009	MAF
inner ear development	1	187.2×	0.012	MAF
microtubule-based movement	1	147.8×	0.012	DYNLRB2
response to nutrient	1	147.8×	0.012	MAF
in utero embryonic development	1	36.0×	0.038	MAF
transcription by RNA polymerase II	1	35.3×	0.038	MAF
positive regulation of gene expression	1	19.4×	0.061	MAF
negative regulation of transcription by RNA polymerase II	1	8.9×	0.120	MAF
regulation of transcription by RNA polymerase II	1	5.8×	0.164	MAF

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
MAF	0	0
DYNLRB2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	MAF, DYNLRB2

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)
MAF	0	—
DYNLRB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.