dilated cardiomyopathy 1II

Summary

dilated cardiomyopathy 1II (MONDO:0014073) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 269

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dilated cardiomyopathy 1II
Mondo ID	MONDO:0014073
OMIM	615184
DOID	DOID:0110450
UMLS	C3554649
MedGen	767563
GARD	0015916
Is cancer (heuristic)	no

Also known as: cardiomyopathy, dilated, 1II · cardiomyopathy, dilated, type 1II · CMD1II · CRYAB familial isolated dilated cardiomyopathy · dilated cardiomyopathy type 1II · familial isolated dilated cardiomyopathy caused by mutation in CRYAB

Data availability: 269 ClinVar variants · 1 GenCC gene-disease record · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › dilated cardiomyopathy › familial dilated cardiomyopathy › familial isolated dilated cardiomyopathy › dilated cardiomyopathy 1II

Related subtypes (44): dilated cardiomyopathy 1A, dilated cardiomyopathy 3B, dilated cardiomyopathy 1B, dilated cardiomyopathy 1E, dilated cardiomyopathy 1C, dilated cardiomyopathy 1D, dilated cardiomyopathy 1G, dilated cardiomyopathy 1H, dilated cardiomyopathy 1I, dilated cardiomyopathy 1K, dilated cardiomyopathy 1L, dilated cardiomyopathy 1M, dilated cardiomyopathy 1O, dilated cardiomyopathy 1P, dilated cardiomyopathy 1Q, dilated cardiomyopathy 1W, dilated cardiomyopathy 1X, dilated cardiomyopathy 1Y, dilated cardiomyopathy 1Z, dilated cardiomyopathy 2A, dilated cardiomyopathy 1AA, dilated cardiomyopathy 1BB, dilated cardiomyopathy 1CC, dilated cardiomyopathy 1DD, dilated cardiomyopathy 1EE, dilated cardiomyopathy 1FF, dilated cardiomyopathy 1R, dilated cardiomyopathy 1S, dilated cardiomyopathy 1GG, dilated cardiomyopathy 1U, dilated cardiomyopathy 1V, dilated cardiomyopathy 1HH, dilated cardiomyopathy 2B, dilated cardiomyopathy 1JJ, dilated cardiomyopathy 1KK, left ventricular noncompaction 8, left ventricular noncompaction 10, dilated cardiomyopathy 1NN, cardiomyopathy, dilated, 2D, cardiomyopathy, dilated, 2E, cardiomyopathy, dilated, 2F, cardiomyopathy, dilated, 2G, cardiomyopathy, dilated, 2c, cardiomyopathy, dilated, 2H

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

269 retrieved; paginated sample, class counts are floors:

161 uncertain significance, 75 likely benign, 15 conflicting classifications of pathogenicity, 8 pathogenic, 6 benign, 2 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070020	NC_000011.9:g.(?111779478)(111782458_?)del	CRYAB	Pathogenic	criteria provided, single submitter
1322163	NM_001289808.2(CRYAB):c.76C>T (p.Gln26Ter)	CRYAB	Pathogenic	criteria provided, single submitter
1392460	NM_001289808.2(CRYAB):c.145del (p.Leu49fs)	CRYAB	Pathogenic	criteria provided, single submitter
1455522	NC_000011.9:g.(?111779488)(111780026_?)del	CRYAB	Pathogenic	criteria provided, single submitter
2424297	NC_000011.9:g.(?111779488)(111782448_?)del	CRYAB	Pathogenic	criteria provided, single submitter
4709887	NM_001289808.2(CRYAB):c.59C>G (p.Pro20Arg)	CRYAB	Pathogenic	criteria provided, single submitter
4721629	NM_001289808.2(CRYAB):c.32_33del (p.Arg11fs)	CRYAB	Pathogenic	criteria provided, single submitter
4736669	NM_001289808.2(CRYAB):c.101del (p.Glu34fs)	CRYAB	Pathogenic	criteria provided, single submitter
265829	NM_001289808.2(CRYAB):c.326A>G (p.Asp109Gly)	CRYAB	Likely pathogenic	criteria provided, single submitter
4687943	NM_001289808.2(CRYAB):c.527A>G (p.Ter176Trp)	CRYAB	Likely pathogenic	criteria provided, single submitter
1069484	NM_001289808.2(CRYAB):c.34C>T (p.Arg12Cys)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1074961	NM_001289808.2(CRYAB):c.295G>T (p.Glu99Ter)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1677811	NM_001289808.2(CRYAB):c.2T>C (p.Met1Thr)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1731612	NM_001289808.2(CRYAB):c.345C>T (p.Ser115=)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178013	NM_001289808.2(CRYAB):c.116C>T (p.Pro39Leu)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
217346	NM_001289808.2(CRYAB):c.320G>T (p.Arg107Leu)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
302431	NM_001289808.2(CRYAB):c.375A>C (p.Pro125=)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3221864	NM_001289808.2(CRYAB):c.69C>G (p.Leu23=)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
380736	NM_001289808.2(CRYAB):c.324+3A>G	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
38963	NM_001289808.2(CRYAB):c.343del (p.Ser115fs)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41926	NM_001289808.2(CRYAB):c.460G>A (p.Gly154Ser)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41929	NM_001289808.2(CRYAB):c.166C>T (p.Arg56Trp)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44232	NM_001289808.2(CRYAB):c.152C>T (p.Pro51Leu)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44236	NM_001289808.2(CRYAB):c.3G>A (p.Met1Ile)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44238	NM_001289808.2(CRYAB):c.487C>T (p.Arg163Cys)	CRYAB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1410524	NC_000011.9:g.(?111779478)(111961866_?)dup	C11orf52	Uncertain significance	criteria provided, single submitter
1007325	NM_001289808.2(CRYAB):c.302A>T (p.His101Leu)	CRYAB	Uncertain significance	criteria provided, single submitter
1007609	NM_001289808.2(CRYAB):c.433G>C (p.Val145Leu)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1014222	NM_001289808.2(CRYAB):c.202A>T (p.Met68Leu)	CRYAB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1018839	NM_001289808.2(CRYAB):c.373C>G (p.Pro125Ala)	CRYAB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 6 · 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
CRYAB	Supportive	Autosomal dominant	familial isolated dilated cardiomyopathy	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRYAB	Orphanet:154	Familial isolated dilated cardiomyopathy
CRYAB	Orphanet:280553	Fatal infantile hypertonic myofibrillar myopathy
CRYAB	Orphanet:399058	Alpha-B crystallin-related late-onset myopathy
CRYAB	Orphanet:441452	Early-onset lamellar cataract
CRYAB	Orphanet:98991	Early-onset nuclear cataract
CRYAB	Orphanet:98993	Early-onset posterior polar 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
CRYAB	HGNC:2389	ENSG00000109846	P02511	Alpha-crystallin B chain	gencc,clinvar
C11orf52	HGNC:30531	ENSG00000149300	Q96A22	Uncharacterized protein C11orf52	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRYAB	Alpha-crystallin B chain	May contribute to the transparency and refractive index of the lens.

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)
CRYAB	Other/Unknown	no		Alpha-crystallin/sHSP_animal, A-crystallin/Hsp20_dom, Alpha-crystallin_N
C11orf52	Other/Unknown	no		DUF4578

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
cardiac ventricle	1
left ventricle myocardium	1
middle frontal gyrus	1
adult mammalian kidney	1
kidney	1
metanephros cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRYAB	289	ubiquitous	marker	middle frontal gyrus, left ventricle myocardium, cardiac ventricle
C11orf52	125	broad	marker	adult mammalian kidney, metanephros cortex, kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRYAB	3,368
C11orf52	574

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRYAB	P02511	21

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C11orf52	Q96A22	61.42

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
HSF1-dependent transactivation	1	317.2×	0.003	CRYAB

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
microtubule polymerization or depolymerization	1	16852.0×	0.001	CRYAB
negative regulation of intracellular transport	1	5617.3×	0.002	CRYAB
regulation of programmed cell death	1	2808.7×	0.002	CRYAB
apoptotic process involved in morphogenesis	1	2808.7×	0.002	CRYAB
tubulin complex assembly	1	1685.2×	0.003	CRYAB
negative regulation of amyloid fibril formation	1	1296.3×	0.003	CRYAB
negative regulation of reactive oxygen species metabolic process	1	936.2×	0.004	CRYAB
stress-activated MAPK cascade	1	702.2×	0.004	CRYAB
protein refolding	1	624.1×	0.004	CRYAB
cellular response to gamma radiation	1	601.9×	0.004	CRYAB
response to hydrogen peroxide	1	468.1×	0.005	CRYAB
negative regulation of protein-containing complex assembly	1	455.5×	0.005	CRYAB
response to heat	1	421.3×	0.005	CRYAB
lens development in camera-type eye	1	374.5×	0.005	CRYAB
glutathione metabolic process	1	351.1×	0.005	CRYAB
muscle contraction	1	208.1×	0.007	CRYAB
response to estradiol	1	198.3×	0.007	CRYAB
muscle organ development	1	166.8×	0.008	CRYAB
negative regulation of cell growth	1	144.0×	0.009	CRYAB
protein folding	1	103.4×	0.012	CRYAB
response to hypoxia	1	95.8×	0.012	CRYAB
negative regulation of gene expression	1	69.1×	0.016	CRYAB
protein stabilization	1	66.9×	0.016	CRYAB
negative regulation of apoptotic process	1	34.8×	0.030	CRYAB
negative regulation of DNA-templated transcription	1	31.6×	0.032	CRYAB

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
CRYAB	0	0
C11orf52	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
CRYAB	13	Binding:13

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	CRYAB, C11orf52

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)
CRYAB	13	—
C11orf52	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.