MYPN-related myopathy

Summary

MYPN-related myopathy (MONDO:0015023) is a disease caused by MYPN (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: MYPN (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 148

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	MYPN-related myopathy
Mondo ID	MONDO:0015023
OMIM	617336
DOID	DOID:0110933
UMLS	C4479186
MedGen	1384302
GARD	0016222
Is cancer (heuristic)	no

Also known as: MYPN nemaline myopathy · MYPN-related myopathy · NEM11 · nemaline myopathy 11 · nemaline myopathy 11, autosomal recessive · nemaline myopathy caused by mutation in MYPN · nemaline myopathy type 11

Data availability: 148 ClinVar variants · 3 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 › nemaline myopathy › MYPN-related myopathy

Related subtypes (7): nemaline myopathy 5, severe congenital nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, nemaline myopathy 5B, autosomal recessive, childhood-onset, nemaline myopathy 5C, autosomal dominant

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

148 retrieved; paginated sample, class counts are floors:

88 uncertain significance, 22 conflicting classifications of pathogenicity, 12 benign/likely benign, 8 benign, 7 pathogenic, 6 likely benign, 4 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1878937	NM_032578.4(MYPN):c.1722dup (p.Lys575fs)	MYPN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2177807	NM_032578.4(MYPN):c.1465C>T (p.Arg489Ter)	MYPN	Pathogenic	criteria provided, multiple submitters, no conflicts
2574646	NM_032578.4(MYPN):c.1973+1G>C	MYPN	Pathogenic	no assertion criteria provided
2574647	NM_032578.4(MYPN):c.1974-2A>C	MYPN	Pathogenic	no assertion criteria provided
375564	NM_032578.4(MYPN):c.2003del (p.Asn668fs)	MYPN	Pathogenic	no assertion criteria provided
375565	NM_032578.4(MYPN):c.3076-2A>C	MYPN	Pathogenic	no assertion criteria provided
375566	NM_032578.4(MYPN):c.1129C>T (p.Arg377Ter)	MYPN	Pathogenic	criteria provided, single submitter
375568	NM_032578.4(MYPN):c.3214C>T (p.Arg1072Ter)	MYPN	Pathogenic	criteria provided, multiple submitters, no conflicts
1804878	NM_032578.4(MYPN):c.55_56del (p.Ser19fs)	MYPN	Likely pathogenic	criteria provided, single submitter
3391086	NM_032578.4(MYPN):c.1903C>T (p.Gln635Ter)	MYPN	Likely pathogenic	criteria provided, single submitter
3896927	NM_032578.4(MYPN):c.2603_2613del (p.Pro868fs)	MYPN	Likely pathogenic	criteria provided, single submitter
3896928	NM_032578.4(MYPN):c.3265del (p.Leu1089fs)	MYPN	Likely pathogenic	criteria provided, single submitter
373730	NM_032578.4(MYPN):c.3073dup (p.Gln1025fs)	LOC132089829	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1063051	NM_032578.4(MYPN):c.650C>T (p.Ala217Val)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1312356	NM_032578.4(MYPN):c.325C>T (p.Pro109Ser)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1766860	NM_032578.4(MYPN):c.94_95del (p.Arg32fs)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180453	NM_032578.4(MYPN):c.3913A>G (p.Met1305Val)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191754	NM_032578.4(MYPN):c.2560T>A (p.Ser854Thr)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191759	NM_032578.4(MYPN):c.3833G>A (p.Arg1278Gln)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
192124	NM_032578.4(MYPN):c.952G>A (p.Val318Ile)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
192126	NM_032578.4(MYPN):c.2863C>T (p.Arg955Trp)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
222748	NM_032578.4(MYPN):c.757G>C (p.Gly253Arg)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
31792	NM_032578.4(MYPN):c.3583G>A (p.Val1195Met)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
31811	NM_032578.4(MYPN):c.59A>G (p.Tyr20Cys)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
31818	NM_032578.4(MYPN):c.2653C>T (p.Arg885Ter)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
431886	NM_032578.4(MYPN):c.3103A>G (p.Met1035Val)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
477747	NM_032578.4(MYPN):c.2165G>A (p.Arg722Gln)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522312	NM_032578.4(MYPN):c.251A>G (p.Asn84Ser)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
544043	NM_032578.4(MYPN):c.3301C>A (p.Pro1101Thr)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
544044	NM_032578.4(MYPN):c.3818C>T (p.Pro1273Leu)	MYPN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · 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
MYPN	Definitive	Autosomal recessive	MYPN-related myopathy	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYPN	Orphanet:154	Familial isolated dilated cardiomyopathy
MYPN	Orphanet:171439	Childhood-onset nemaline myopathy
MYPN	Orphanet:171881	Cap myopathy
MYPN	Orphanet:75249	Familial isolated restrictive cardiomyopathy

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
MYPN	HGNC:23246	ENSG00000138347	Q86TC9	Myopalladin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYPN	Myopalladin	Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYPN	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
hindlimb stylopod muscle	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYPN	116	broad	marker	hindlimb stylopod muscle, gastrocnemius, vastus lateralis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYPN	1,764

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MYPN	Q86TC9	52.71

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
dendrite self-avoidance	1	1053.2×	0.004	MYPN
sarcomere organization	1	383.0×	0.005	MYPN
homophilic cell-cell adhesion	1	140.4×	0.009	MYPN
axon guidance	1	90.6×	0.011	MYPN

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
MYPN	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	1	MYPN
E	Difficult family or no structure, no drug	0

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)
MYPN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.