Myofibrillar myopathy 11

Summary

Myofibrillar myopathy 11 (MONDO:0030927) is a disease caused by UNC45B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: UNC45B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myofibrillar myopathy 11
Mondo ID	MONDO:0030927
OMIM	619178
DOID	DOID:0081338
UMLS	C5543038
MedGen	1782465
GARD	0025664
Is cancer (heuristic)	no

Also known as: MFM11 · myopathy, congenital, with eccentric cores

Data availability: 14 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › congenital structural myopathy › myofibrillar myopathy › myofibrillar myopathy 11

Related subtypes (12): central core myopathy, myofibrillar myopathy 1, myofibrillar myopathy 3, myofibrillar myopathy 4, myofibrillar myopathy 5, myofibrillar myopathy 6, fatal infantile hypertonic myofibrillar myopathy, myofibrillar myopathy 7, myofibrillar myopathy 8, myofibrillar myopathy 10, myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy, myopathy, myofibrillar, 13, with rimmed vacuoles

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

14 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 2 pathogenic, 2 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
834072	NM_001267052.2(UNC45B):c.2255G>A (p.Arg752Gln)	UNC45B	Pathogenic	criteria provided, multiple submitters, no conflicts
996756	NM_001267052.2(UNC45B):c.1540T>C (p.Cys514Arg)	UNC45B	Pathogenic	no assertion criteria provided
996754	NM_001267052.2(UNC45B):c.2326C>T (p.Arg776Trp)	UNC45B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
996755	NM_001267052.2(UNC45B):c.2255+5G>C	UNC45B	Likely pathogenic	criteria provided, single submitter
2441785	NM_001267052.2(UNC45B):c.73G>A (p.Ala25Thr)	UNC45B	Uncertain significance	criteria provided, single submitter
2683907	NM_001267052.2(UNC45B):c.2293G>A (p.Glu765Lys)	UNC45B	Uncertain significance	criteria provided, single submitter
3186553	NM_001267052.2(UNC45B):c.1487A>T (p.Asp496Val)	UNC45B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3775861	NM_001267052.2(UNC45B):c.2374G>A (p.Val792Ile)	UNC45B	Uncertain significance	criteria provided, single submitter
3892816	NM_001267052.2(UNC45B):c.135T>G (p.Leu45=)	UNC45B	Uncertain significance	criteria provided, single submitter
3892817	NM_001267052.2(UNC45B):c.2408G>A (p.Arg803Gln)	UNC45B	Uncertain significance	criteria provided, single submitter
3892818	NM_001267052.2(UNC45B):c.2558G>A (p.Arg853Gln)	UNC45B	Uncertain significance	criteria provided, single submitter
3892819	NM_001267052.2(UNC45B):c.442_443del (p.Glu148fs)	UNC45B	Uncertain significance	criteria provided, single submitter
996753	NM_001267052.2(UNC45B):c.1207T>C (p.Ser403Pro)	UNC45B	Uncertain significance	criteria provided, single submitter
1220664	NM_001267052.2(UNC45B):c.808+39G>A	UNC45B	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
UNC45B	Strong	Autosomal recessive	myofibrillar myopathy 11	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UNC45B	Orphanet:441447	Early-onset posterior subcapsular cataract
UNC45B	Orphanet:98991	Early-onset nuclear 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
UNC45B	HGNC:14304	ENSG00000141161	Q8IWX7	Protein unc-45 homolog B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UNC45B	Protein unc-45 homolog B	Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UNC45B	Other/Unknown	no		Armadillo, ARM-like, TPR-like_helical_dom_sf

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac muscle of right atrium	1
left ventricle myocardium	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UNC45B	111	tissue_specific	yes	left ventricle myocardium, cardiac muscle of right atrium, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UNC45B	1,273

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UNC45B	Q8IWX7	88.38

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
lens development in camera-type eye	1	374.5×	0.011	UNC45B
muscle organ development	1	166.8×	0.012	UNC45B
protein folding	1	103.4×	0.013	UNC45B
cell differentiation	1	29.1×	0.034	UNC45B

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
UNC45B	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	UNC45B

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)
UNC45B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.