MYMK

Summary

MYMK (myomaker, myoblast fusion factor, HGNC:33778) is a protein-coding gene on chromosome 9q34.2, encoding Protein myomaker (A6NI61). Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers.

Involved in myoblast fusion. Located in plasma membrane. Implicated in Carey-Fineman-Ziter syndrome.

Source: NCBI Gene 389827 — RefSeq curated summary.

At a glance

• Gene–disease (curated): obsolete Carey-Fineman-Ziter syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 81 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 79
• MANE Select transcript: NM_001080483

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33778
Approved symbol	MYMK
Name	myomaker, myoblast fusion factor
Location	9q34.2
Locus type	gene with protein product
Status	Approved
Aliases	TMEM226, MYOMAKER
Ensembl gene	ENSG00000187616
Ensembl biotype	protein_coding
OMIM	615345
Entrez	389827

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000339996, ENST00000413714

RefSeq mRNA: 1 — MANE Select: NM_001080483 NM_001080483

CCDS: CCDS35170

Canonical transcript exons

ENST00000339996 — 5 exons

Exon	Start	End
ENSE00001379793	133514586	133514785
ENSE00001382418	133515491	133515607
ENSE00001390271	133524710	133524959
ENSE00003549107	133518874	133519022
ENSE00003562716	133520174	133520288

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 55.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7982 / max 133.7261, expressed in 69 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103014	0.7982	69

Top tissues by expression

111 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	55.93	gold quality
metanephros cortex	UBERON:0010533	49.78	gold quality
putamen	UBERON:0001874	47.86	gold quality
placenta	UBERON:0001987	47.48	gold quality
right lung	UBERON:0002167	47.26	gold quality
bone marrow cell	CL:0002092	45.99	silver quality
adult mammalian kidney	UBERON:0000082	45.64	gold quality
substantia nigra	UBERON:0002038	43.94	gold quality
sural nerve	UBERON:0015488	43.34	silver quality
cortex of kidney	UBERON:0001225	43.31	gold quality
kidney	UBERON:0002113	43.05	gold quality
gastrocnemius	UBERON:0001388	42.48	gold quality
colonic epithelium	UBERON:0000397	41.60	gold quality
muscle of leg	UBERON:0001383	41.33	gold quality
skeletal muscle tissue	UBERON:0001134	40.86	silver quality
prefrontal cortex	UBERON:0000451	39.57	gold quality
islet of Langerhans	UBERON:0000006	39.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	39.06	gold quality
right atrium auricular region	UBERON:0006631	38.49	gold quality
right uterine tube	UBERON:0001302	38.32	silver quality
bone marrow	UBERON:0002371	38.06	silver quality
Ammon’s horn	UBERON:0001954	38.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	37.90	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	36.04	gold quality
frontal cortex	UBERON:0001870	35.86	gold quality
caudate nucleus	UBERON:0001873	35.77	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
superior frontal gyrus	UBERON:0002661	34.92	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• The data establish that MYMK activity is necessary for normal muscle development and maintenance in humans and zebrafish, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits. (PMID:28681861)
• This articles reviews and discusses the latest studies related to Myomaker and Myomixer-Myomerger-Minion, including the discovery, structure, expression pattern, functions of the two proteins. [review] (PMID:31642939)
• Can we talk about myoblast fusion? (PMID:34288723)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mymk	ENSDARG00000103988
mus_musculus	Mymk	ENSMUSG00000009214
rattus_norvegicus	Mymk	ENSRNOG00000006142

Paralogs (2): PGAP6 (ENSG00000129925), TMEM8B (ENSG00000137103)

Protein

Protein identifiers

Protein myomaker — A6NI61 (reviewed: A6NI61)

Alternative names: Myoblast fusion maker, Transmembrane protein 226, Transmembrane protein 8C

All UniProt accessions (1): A6NI61

UniProt curated annotations — full annotation on UniProt →

Function. Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers. Actively participates in the membrane fusion reaction by mediating the mixing of cell membrane lipids (hemifusion) upstream of MYMX. Acts independently of MYMX. Involved in skeletal muscle regeneration in response to injury by mediating the fusion of satellite cells, a population of muscle stem cells, with injured myofibers. Also involved in skeletal muscle hypertrophy, probably by mediating the fusion of satellite cells with myofibers.

Subunit / interactions. Interacts with MYMX.

Subcellular location. Cell membrane. Golgi apparatus membrane.

Post-translational modifications. Palmitoylated at the C-terminus; palmitoylation promotes localization to the Golgi apparatus.

Disease relevance. Carey-Fineman-Ziter syndrome 1 (CFZS1) [MIM:254940] An autosomal recessive multisystem disorder characterized by hypotonia, bilateral congenital facial palsy with impairment of ocular abduction (Moebius sequence), micrognathia, glossoptosis and high-arched or cleft palate (Pierre Robin complex), delayed motor milestones, and failure to thrive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TMEM8 family.

RefSeq proteins (1): NP_001073952* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021910	NGX6/PGAP6/MYMK	Family

Pfam: PF12036

UniProt features (23 total): topological domain 8, transmembrane region 7, sequence variant 5, lipid moiety-binding region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NI61-F1	91.14	0.80

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 217, 218

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 211 (showing top): GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_SKELETAL_MUSCLE_ADAPTATION, GOBP_MEMBRANE_FUSION, GOBP_GROWTH, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGENERATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_MUSCLE_HYPERTROPHY, GOBP_MUSCLE_ADAPTATION, GOBP_REGULATION_OF_MUSCLE_HYPERTROPHY, GOBP_TISSUE_REGENERATION, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_REGULATION_OF_SKELETAL_MUSCLE_ADAPTATION, GOBP_REGULATION_OF_SYSTEM_PROCESS

GO Biological Process (6): muscle organ development (GO:0007517), myoblast fusion (GO:0007520), myoblast fusion involved in skeletal muscle regeneration (GO:0014905), obsolete plasma membrane fusion (GO:0045026), positive regulation of skeletal muscle hypertrophy (GO:1904206), skeletal muscle tissue regeneration (GO:0043403)

GO Molecular Function (0):

GO Cellular Component (4): Golgi membrane (GO:0000139), plasma membrane (GO:0005886), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	1
muscle structure development	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
myoblast fusion	1
myotube differentiation involved in skeletal muscle regeneration	1
skeletal muscle tissue regeneration	1
skeletal muscle hypertrophy	1
positive regulation of muscle hypertrophy	1
positive regulation of muscle adaptation	1
regulation of skeletal muscle hypertrophy	1
tissue regeneration	1
Golgi apparatus	1
bounding membrane of organelle	1
membrane	1
cell periphery	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

420 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYMK	MYMX	A0A1B0GTQ4	961
MYMK	MYOG	P15173	743
MYMK	MYOD1	P15172	672
MYMK	MYF6	P23409	632
MYMK	MYF5	P13349	614
MYMK	PAX7	P23759	594
MYMK	MYH8	P13535	575
MYMK	MYH3	P11055	570
MYMK	ADGRB3	O60242	493
MYMK	MYH6	P13533	483
MYMK	COL6A3	P12111	449
MYMK	MYH4	Q9Y623	423
MYMK	ADGRB1	O14514	423
MYMK	DOCK1	Q14185	418
MYMK	MYH1	P12882	405

IntAct

0 interactions, top by confidence:

BioGRID (1): GSTO1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GVZ9, A4IFN5, A5PK40, A6NH52, A6NI61, B2LYG4, B2RZC9, B6ID01, D2HKB0, D3ZG27, P86229, Q0VDI3, Q15012, Q15546, Q17QJ2, Q1RLT2, Q2TA01, Q4R4I5, Q4R6E8, Q5H8A4, Q5R7Q1, Q5RAH0, Q5RL79, Q5U3C3, Q5VTY9, Q5ZML7, Q64232, Q6PHN7, Q6QRN8, Q719N3, Q71SV0, Q8BWB6, Q8IY49, Q8N6M3, Q8NFT2, Q8R189, Q8VD53, Q8VDI9, Q8VDR5, Q9CQC4

Diamond homologs: A6NDV4, A6NI61, A6QLK4, B1AWJ5, Q6IQ69, Q9D1N4, Q9ESN3, Q9HCN3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

81 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	44
Likely benign	10
Benign	17

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
430840	NM_001080483.3(MYMK):c.553T>C (p.Cys185Arg)	Pathogenic
430842	NM_001080483.3(MYMK):c.2T>A (p.Met1Lys)	Pathogenic
430843	NM_001080483.3(MYMK):c.461T>C (p.Ile154Thr)	Pathogenic
4759237	NM_001080483.3(MYMK):c.457C>T (p.Gln153Ter)	Pathogenic
4532817	NM_001080483.3(MYMK):c.586C>T (p.Pro196Ser)	Likely pathogenic
870390	NM_001080483.3(MYMK):c.305T>C (p.Leu102Pro)	Likely pathogenic

SpliceAI

1181 predictions. Top by Δscore:

Variant	Effect	Δscore
9:133515485:TGGTA:T	donor_loss	1.0000
9:133515486:GGTAC:G	donor_loss	1.0000
9:133515487:GTACC:G	donor_loss	1.0000
9:133515488:TACCT:T	donor_loss	1.0000
9:133515489:A:C	donor_loss	1.0000
9:133515490:C:CG	donor_loss	1.0000
9:133515605:TAG:T	acceptor_gain	1.0000
9:133515606:AG:A	acceptor_gain	1.0000
9:133515607:GC:G	acceptor_loss	1.0000
9:133515608:C:CA	acceptor_loss	1.0000
9:133515608:C:CC	acceptor_gain	1.0000
9:133515617:C:CT	acceptor_gain	1.0000
9:133515618:A:T	acceptor_gain	1.0000
9:133518871:CACC:C	donor_loss	1.0000
9:133518872:A:C	donor_loss	1.0000
9:133518873:CCCA:C	donor_gain	1.0000
9:133518876:A:AC	donor_gain	1.0000
9:133518877:C:CC	donor_gain	1.0000
9:133519018:CAGTG:C	acceptor_gain	1.0000
9:133519019:AGTG:A	acceptor_gain	1.0000
9:133519020:GTG:G	acceptor_gain	1.0000
9:133519021:TG:T	acceptor_gain	1.0000
9:133519023:C:CC	acceptor_gain	1.0000
9:133519023:CT:C	acceptor_loss	1.0000
9:133519024:T:G	acceptor_loss	1.0000
9:133519033:C:CT	acceptor_gain	1.0000
9:133519033:C:T	acceptor_gain	1.0000
9:133519034:A:T	acceptor_gain	1.0000
9:133524705:CT:C	donor_loss	1.0000
9:133524706:TCA:T	donor_loss	1.0000

AlphaMissense

1439 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:133514759:G:C	S181R	0.998
9:133514759:G:T	S181R	0.998
9:133514761:T:G	S181R	0.998
9:133520193:G:C	S77R	0.997
9:133520193:G:T	S77R	0.997
9:133520195:T:G	S77R	0.997
9:133524803:G:C	S14R	0.997
9:133524803:G:T	S14R	0.997
9:133524805:T:G	S14R	0.997
9:133520189:A:G	W79R	0.994
9:133520189:A:T	W79R	0.994
9:133515537:C:T	G157D	0.990
9:133518974:C:T	G100D	0.990
9:133520207:C:A	G73W	0.987
9:133524771:G:T	A25E	0.987
9:133524800:G:C	S15R	0.987
9:133524800:G:T	S15R	0.987
9:133524802:T:G	S15R	0.987
9:133515543:C:T	G155D	0.986
9:133518975:C:G	G100R	0.985
9:133520207:C:G	G73R	0.985
9:133520207:C:T	G73R	0.985
9:133515532:A:G	C159R	0.984
9:133515538:C:G	G157R	0.982
9:133524745:C:G	A34P	0.982
9:133524756:A:G	F30S	0.982
9:133518905:C:T	G123D	0.980
9:133524804:C:T	S14N	0.979
9:133520206:C:T	G73E	0.978
9:133515526:C:G	G161R	0.977

dbSNP variants (sampled 300 via entrez): RS1000010646 (9:133522872 G>C), RS1000130584 (9:133517858 C>T), RS1000327716 (9:133520025 C>A,T), RS1000436247 (9:133525221 T>A), RS1000481285 (9:133517580 C>T), RS1000969274 (9:133515336 C>T), RS1001998479 (9:133521163 T>C), RS1002162512 (9:133526239 C>A), RS1002231350 (9:133516296 A>G), RS1002252190 (9:133517961 C>T), RS1002492912 (9:133522988 C>G,T), RS1002513533 (9:133526512 C>A), RS1002527341 (9:133524332 G>A,T), RS1002583787 (9:133516560 C>T), RS1003093171 (9:133514490 A>C,G)

Disease associations

OMIM: gene MIM:615345 | disease phenotypes: MIM:254940

GenCC curated gene-disease

Disease	Classification	Inheritance
Carey-Fineman-Ziter syndrome	Definitive	Autosomal recessive
Carey-Fineman-Ziter syndrome 1	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
obsolete Carey-Fineman-Ziter syndrome	Definitive	AR

Mondo (3): Carey-Fineman-Ziter syndrome (MONDO:0031415), Carey-Fineman-Ziter syndrome 1 (MONDO:0800437), (MONDO:0009700)

Orphanet (1): Carey-Fineman-Ziter syndrome (Orphanet:1358)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000126	Hydronephrosis
HP:0000162	Glossoptosis
HP:0000171	Microglossia
HP:0000175	Cleft palate
HP:0000201	Pierre-Robin sequence
HP:0000211	Trismus
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000602	Ophthalmoplegia
HP:0000634	Impaired ocular abduction
HP:0000807	Glanular hypospadias
HP:0001156	Brachydactyly
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008839_234	Height	2.000000e-10
GCST012521_2	ABO blood group (A vs non-A)	5.000000e-08
GCST90000025_384	Appendicular lean mass	8.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0600060	blood group A
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536102	Myopathy, congenital nonprogressive with Moebius and Robin sequences (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.