MYMK

protein-coding

myomaker, myoblast fusion factor, the group of TMEM8 family

Gene summary

Involved in myoblast fusion. Located in plasma membrane. Implicated in Carey-Fineman-Ziter syndrome 1. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

TMEM8C

MANE transcript

NM_001080483.3

Inheritance

ClinVar variants

P:9U:45B:13

Top phenotype

Carey-Fineman-Ziter syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr9:133,514,586-133,528,612

External References & Databases

Ensembl (ENSG00000187616)

Transcript & Mutation Effects

hg38 • Region Span ~14.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Carey-Fineman-Ziter syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0800437

Submitter: PanelApp Australia

Carey-Fineman-Ziter syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009700

Submitter: Illumina

The MYMK gene, previously referred to as TMEM8C, is located on chromosome 9 at 9q34.2 and encodes the transmembrane Myomaker protein, which is required for myoblast fusion and the formation of multinucleated myofibers during skeletal muscle development and regeneration. The MYMK gene was first reported in relation to autosomal recessive Carey-Fineman-Ziter syndrome in 2017 (28681861: Di Gioia et al. 2017). At least six unique variants, all missense, have been reported in humans. A majority of individuals carry one copy of the p.Pro91Thr variant. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in seven unrelated probands in three publications (28681861: Di Gioia et al. 2017; 29560417: Alrohaif et al. 2018; 30065953: Hedberg-Oldfors et al. 2018). Variants in this gene segregated with disease in five additional family members, but none of the families met criteria for scoring segregation. Homozygous loss of function is implicated as the mechanism of disease. This gene-disease relationship is also supported by expression data, in vitro functional analyses of reported variants, mouse and zebrafish models, and rescue in the zebrafish model (23868259: Millay et al. 2013; 28681861: Di Gioia et al. 2017). In summary, there is strong evidence to support the relationship between MYMK and Carey-Fineman-Ziter syndrome, autosomal recessive. An additional report in humans published three years from the first proposal of the association is needed to reach a definitive classification.

Carey-Fineman-Ziter syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009700

Submitter: ClinGen

The MYMK gene, previously referred to as TMEM8C, is located on chromosome 9 at 9q34.2 and encodes the transmembrane Myomaker protein, which is required for myoblast fusion and the formation of multinucleated myofibers during skeletal muscle development and regeneration. The MYMK gene was first reported in relation to autosomal recessive Carey-Fineman-Ziter syndrome in 2017 (Di Gioia et al., PMID: 28681861). One initiation codon, one non-canonical splice site, and six unique missense alleles have been reported in humans. A majority of individuals carry one copy of the p.Pro91Thr variant. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in nine unrelated probands in five publications (PMID: 28681861; Alrohaif et al., 2018, PMID:29560417; Hedberg-Oldfors et al., 2018, PMID:30065953; Camacho et al., 2020, PMID:32333597; Lunke et al., 2020, PMID:32573669). Variants in this gene segregated with disease in five additional family members, but none of the families met criteria for scoring segregation. Homozygous loss of function is implicated as the mechanism of disease. This gene-disease relationship is also supported by expression data, in vitro functional analyses of reported variants, mouse and zebrafish models, and rescue in the zebrafish model (Millay et al., 2013, PMID:23868259; PMID: 28681861). In summary, MYMK is definitively associated with autosomal recessive Carey-Fineman-Ziter syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Syndromic Disorders Gene Curation Expert Panel on the meeting date 03.02.2022 (SOP Version 8).

Carey-Fineman-Ziter syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009700

Submitter: Orphanet

Carey-Fineman-Ziter syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0800437

Submitter: Labcorp Genetics (formerly Invitae)

Carey-Fineman-Ziter syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009700

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Carey-Fineman-Ziter syndrome 1AR

Manifestation: Craniofacial; Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28681861; 29560417

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYMK variants in ClinVar

9 Conditions Cataloged

Inborn genetic diseasesTotal: 34

not providedTotal: 25

Congenital nonprogressive myopathy with Moebius and Robin sequencesTotal: 10

Carey-Fineman-Ziter syndrome 1Total: 7

MYMK-related disorderTotal: 5

TMEM8C-related disordersTotal: 2

not specifiedTotal: 2

Fetal anomalies with a likely genetic causeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080483.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				11 clinvar	2 clinvar	13
missense	3 clinvar	4 clinvar	43 clinvar			50
nonsense	1 clinvar					1
start loss	1 clinvar					1
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	5	4	45	11	2	67

Highest pathogenic variant AF is 0.001917043

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080483.3	RefSeq	NP_001073952.1	5	MANE Select
ENST00000339996.4	Ensembl	ENSP00000419712.2	5	MANE Select
ENST00001139478.1	Ensembl	ENSP00000813429.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mymk	Danio rerio	Structure: fast muscle myoblast Quality: nucleate quality abnormal

Gene / Model

Organism

Observed Phenotype

mymk

Danio rerio

Structure: fast muscle myoblast

Quality: nucleate quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

muscle organ development
myoblast fusion
myoblast fusion involved in skeletal muscle regeneration
plasma membrane fusion

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339996
Coding exons: 5
Length: 14027
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.761	119	145	0.822	0.00000895	1434
Missense (PolyPhen)		40	53.917	0.74188		498
Synonymous	0.204	64	66.1	0.968	0.00000481	454
Loss of Function	0.936	7	10.2	0.684	5.24e-7	106

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. Associates with MYMX to promote myoblast fusion. {ECO:0000269|PubMed:28681861}.;
Disease: DISEASE: Carey-Fineman-Ziter syndrome (CFZS) [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. {ECO:0000269|PubMed:28681861}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: -0.29
RVIS percentile EVS: 32.94

Essentials

Essential (gene trap): N