Myopathy, centronuclear, 6, with fiber-type disproportion

Summary

Myopathy, centronuclear, 6, with fiber-type disproportion (MONDO:0054695) is a disease caused by MAP3K20 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: MAP3K20 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy, centronuclear, 6, with fiber-type disproportion
Mondo ID	MONDO:0054695
OMIM	617760
DOID	DOID:0111221
UMLS	C4540345
MedGen	1627492
GARD	0016250
Is cancer (heuristic)	no

Also known as: CNM6 · myopathy, centronuclear, 6, with fiber-type disproportion

Data availability: 9 ClinVar variants · 2 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 › centronuclear myopathy › myopathy, centronuclear, 6, with fiber-type disproportion

Related subtypes (4): autosomal dominant centronuclear myopathy, X-linked myotubular myopathy, congenital myopathy with internal nuclei and atypical cores, autosomal recessive centronuclear myopathy

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

9 retrieved; paginated sample, class counts are floors:

5 benign, 2 pathogenic, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
446158	NM_016653.3(MAP3K20):c.490_491del (p.Met164fs)	MAP3K20	Pathogenic	criteria provided, single submitter
446159	NM_016653.3(MAP3K20):c.515G>A (p.Trp172Ter)	MAP3K20	Pathogenic	criteria provided, single submitter
446160	NM_016653.3(MAP3K20):c.282dup (p.Asn95Ter)	MAP3K20	Pathogenic/Likely pathogenic	no assertion criteria provided
1263549	NM_016653.3(MAP3K20):c.445-37A>G	MAP3K20	Benign	criteria provided, multiple submitters, no conflicts
1268264	NM_016653.3(MAP3K20):c.1592C>T (p.Ser531Leu)	MAP3K20	Benign	criteria provided, multiple submitters, no conflicts
1269021	NM_016653.3(MAP3K20):c.1032+39G>A	MAP3K20	Benign	criteria provided, multiple submitters, no conflicts
1279579	NM_016653.3(MAP3K20):c.1360-28A>G	MAP3K20	Benign	criteria provided, multiple submitters, no conflicts
1178388	NM_016653.3(MAP3K20):c.670-11G>C	MAP3K20-AS1	Benign	criteria provided, multiple submitters, no conflicts
1229230	NM_016653.3(MAP3K20):c.1360-14_1360-9del	MAP3K20-AS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
MAP3K20	Strong	Autosomal recessive	myopathy, centronuclear, 6, with fiber-type disproportion	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAP3K20	Orphanet:2020	Congenital fiber-type disproportion myopathy
MAP3K20	Orphanet:488232	Split-foot malformation-mesoaxial polydactyly syndrome

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
MAP3K20	HGNC:17797	ENSG00000091436	Q9NYL2	Mitogen-activated protein kinase kinase kinase 20	gencc,clinvar
MAP3K20-AS1	HGNC:27935	ENSG00000238133		MAP3K20 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAP3K20	Mitogen-activated protein kinase kinase kinase 20	Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAP3K20	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, SAM
MAP3K20-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
heart right ventricle	1
skeletal muscle tissue of rectus abdominis	1
bone marrow cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAP3K20	267	ubiquitous	marker	heart right ventricle, skeletal muscle tissue of rectus abdominis, biceps brachii
MAP3K20-AS1	147	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAP3K20	1,615
MAP3K20-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAP3K20	Q9NYL2	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
negative regulation of stress-activated protein kinase signaling cascade	1	16852.0×	7e-04	MAP3K20
positive regulation of mitotic DNA damage checkpoint	1	16852.0×	7e-04	MAP3K20
negative regulation of translation in response to endoplasmic reticulum stress	1	5617.3×	0.001	MAP3K20
GCN2-mediated signaling	1	4213.0×	0.001	MAP3K20
stress-activated protein kinase signaling cascade	1	2407.4×	0.002	MAP3K20
cell death	1	2106.5×	0.002	MAP3K20
cellular response to UV-B	1	1404.3×	0.003	MAP3K20
positive regulation of programmed cell death	1	1123.5×	0.003	MAP3K20
p38MAPK cascade	1	887.0×	0.003	MAP3K20
stress-activated MAPK cascade	1	702.2×	0.004	MAP3K20
cellular response to gamma radiation	1	601.9×	0.004	MAP3K20
pyroptotic inflammatory response	1	510.7×	0.004	MAP3K20
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.004	MAP3K20
limb development	1	411.0×	0.004	MAP3K20
DNA damage checkpoint signaling	1	391.9×	0.004	MAP3K20
embryonic digit morphogenesis	1	300.9×	0.005	MAP3K20
JNK cascade	1	271.8×	0.005	MAP3K20
chromosome segregation	1	173.7×	0.008	MAP3K20
MAPK cascade	1	153.2×	0.009	MAP3K20
protein autophosphorylation	1	145.3×	0.009	MAP3K20
cytoskeleton organization	1	132.7×	0.009	MAP3K20
protein phosphorylation	1	68.0×	0.017	MAP3K20
positive regulation of apoptotic process	1	56.7×	0.019	MAP3K20
inflammatory response	1	37.7×	0.028	MAP3K20
cell differentiation	1	29.1×	0.034	MAP3K20

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MAP3K20	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAP3K20	53	4
MAP3K20-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	MAP3K20
VEMURAFENIB	4	MAP3K20
FEDRATINIB	4	MAP3K20
AXITINIB	4	MAP3K20
SORAFENIB	4	MAP3K20
DASATINIB ANHYDROUS	4	MAP3K20
NERATINIB	4	MAP3K20
IBRUTINIB	4	MAP3K20
REGORAFENIB	4	MAP3K20
DABRAFENIB	4	MAP3K20
PACRITINIB	4	MAP3K20
VANDETANIB	4	MAP3K20
NILOTINIB	4	MAP3K20
BOSUTINIB	4	MAP3K20
ENCORAFENIB	4	MAP3K20
TOVORAFENIB	4	MAP3K20
DASATINIB	4	MAP3K20
QUIZARTINIB	4	MAP3K20
IMATINIB	4	MAP3K20
VATALANIB	3	MAP3K20
MASITINIB	3	MAP3K20
SARACATINIB	3	MAP3K20
LINIFANIB	3	MAP3K20
RIVOCERANIB	3	MAP3K20
CANERTINIB	3	MAP3K20
DOVITINIB	3	MAP3K20
MOTESANIB	3	MAP3K20
LESTAURTINIB	3	MAP3K20
DORAMAPIMOD	2	MAP3K20
FORETINIB	2	MAP3K20

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MAP3K20	245	Binding:244, Functional:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MAP3K20	245

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

30 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.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	MAP3K20
VEMURAFENIB	4	MAP3K20
FEDRATINIB	4	MAP3K20
AXITINIB	4	MAP3K20
SORAFENIB	4	MAP3K20
DASATINIB ANHYDROUS	4	MAP3K20
NERATINIB	4	MAP3K20
IBRUTINIB	4	MAP3K20
REGORAFENIB	4	MAP3K20
DABRAFENIB	4	MAP3K20
PACRITINIB	4	MAP3K20
VANDETANIB	4	MAP3K20
NILOTINIB	4	MAP3K20
BOSUTINIB	4	MAP3K20
ENCORAFENIB	4	MAP3K20
TOVORAFENIB	4	MAP3K20
DASATINIB	4	MAP3K20
QUIZARTINIB	4	MAP3K20
IMATINIB	4	MAP3K20
VATALANIB	3	MAP3K20
MASITINIB	3	MAP3K20
SARACATINIB	3	MAP3K20
LINIFANIB	3	MAP3K20
RIVOCERANIB	3	MAP3K20
CANERTINIB	3	MAP3K20
DOVITINIB	3	MAP3K20
MOTESANIB	3	MAP3K20
LESTAURTINIB	3	MAP3K20
DORAMAPIMOD	2	MAP3K20
FORETINIB	2	MAP3K20

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MAP3K20
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	MAP3K20-AS1

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)
MAP3K20-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.