MYH8

protein-coding

myosin heavy chain 8, the group of Myosin heavy chains, class II

Gene summary

Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

MANE transcript

NM_002472.3

Inheritance

ClinVar variants

P:3U:345B:118

Top phenotype

Carney complex variant; Arthrogryposis, distal, type 7 (Trismus-pseudocamptodactyly syndrome)

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr17:10,390,322-10,421,950

External References & Databases

Ensembl (ENSG00000133020)

Transcript & Mutation Effects

hg38 • Region Span ~31.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

trismus-pseudocamptodactyly syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008016

Submitter: Ambry Genetics

trismus-pseudocamptodactyly syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008016

Submitter: PanelApp Australia

trismus-pseudocamptodactyly syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008016

Submitter: G2P

trismus-pseudocamptodactyly syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008016

Submitter: Labcorp Genetics (formerly Invitae)

trismus-pseudocamptodactyly syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008016

Submitter: Orphanet

Carney complex - trismus - pseudocamptodactyly syndromeNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0012137

Submitter: G2P

Clinical Genomic Database (CGD)

Carney complex variant; Arthrogryposis, distal, type 7 (Trismus-pseudocamptodactyly syndrome)AD

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

Comments: In one family, cardiac and dermatologic findings appeared to co-segregate with the disease

Refs: 4443857; 4837286; 12800911; 15590965; 15282353; 17041932; 18049072; 20949528

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYH8 variants in ClinVar

12 Conditions Cataloged

not specifiedTotal: 327

not providedTotal: 168

Hecht syndromeTotal: 108

MYH8-related disorderTotal: 36

Carney complex - trismus - pseudocamptodactyly syndromeTotal: 13

Neuromuscular diseaseTotal: 2

Arthrogryposis, distal, type 1ATotal: 2

Inborn genetic diseasesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002472.3. 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			18 clinvar	58 clinvar	4 clinvar	80
missense	1 clinvar		307 clinvar	42 clinvar	5 clinvar	355
nonsense		1 clinvar	7 clinvar	3 clinvar		11
start loss						0
frameshift			7 clinvar	3 clinvar		10
splice donor/acceptor (+/-2bp)		1 clinvar	6 clinvar	3 clinvar		10
Total	1	2	345	109	9	466

Highest pathogenic variant AF is 0.000022308315

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002472.3	RefSeq	NP_002463.2	38	MANE Select
ENST00000403437.2	Ensembl	ENSP00000384330.2	38	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)
Striated Muscle Contraction
Striated Muscle Contraction
Muscle contraction

Biological Process

skeletal muscle contraction
protein dephosphorylation
muscle contraction
muscle filament sliding
ATP metabolic process

Molecular Function

microfilament motor activity
calmodulin binding
ATP binding
structural constituent of muscle
ATPase activity

Cellular Component

cytoplasm
cytosol
muscle myosin complex
sarcomere
myosin filament

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403437
Coding exons: 38
Length: 31629
Individuals with no LoFs: 124610
Homozygous LoFs: 4
Heterozygous LoFs: 1134
Defined: 125748
p: 0.00454

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.350	965	996	0.969	0.0000595	12871
Missense (PolyPhen)		357	361.73	0.98692		4950
Synonymous	-0.682	399	382	1.04	0.0000228	3509
Loss of Function	1.30	86	100	0.860	0.00000532	1282

Population LoF Frequency

Population	CAF	p-value	Status
African	0.012	0.012	notable
Latino/Admixed American	0.0023	0.0023	notable
Ashkenazi Jewish	0.0037	0.0037	notable
East Asian	0.012	0.012	notable
Finnish	0.0026	0.0026	notable
European (Non-Finnish)	0.0037	0.0037	notable
South Asian	0.0034	0.0033	notable
Other	0.0039	0.0039	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Muscle contraction.;
Disease: DISEASE: Carney complex variant (CACOV) [MIM:608837]: Carney complex is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas. Familial cardiac myxomas are associated with spotty pigmentation of the skin and other phenotypes, including primary pigmented nodular adrenocortical dysplasia, extracardiac (frequently cutaneous) myxomas, schwannomas, and pituitary, thyroid, testicular, bone, ovarian, and breast tumors. Cardiac myxomas do not develop in all patients with the Carney complex, but affected patients have at least two features of the complex or one feature and a clinically significant family history. {ECO:0000269|PubMed:15282353}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Arthrogryposis, distal, 7 (DA7) [MIM:158300]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA7 is characterized by an inability to open the mouth fully (trismus) and pseudocamptodactyly in which wrist dorsiflexion, but not volarflexion, produces involuntary flexion contracture of distal and proximal interphalangeal joints. Additional features include shortened hamstring muscles and short stature. {ECO:0000269|PubMed:15282353, ECO:0000269|PubMed:20949528}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.187

Intolerance Scores

LoFtool: 0.139
RVIS EVS: -0.69
RVIS percentile EVS: 15.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.214

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High