MYH10

protein-coding

myosin heavy chain 10, the group of Myosin heavy chains, class II

Gene summary

This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-10 (MYO10). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene have been associated with May-Hegglin anomaly and developmental defects in brain and heart. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MANE transcript

NM_001256012.3

Inheritance

ClinVar variants

P:20U:335B:53

Top phenotype

complex neurodevelopmental disorder with or without congenital anomalies

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr17:8,474,207-8,631,376

External References & Databases

Ensembl (ENSG00000133026)

Transcript & Mutation Effects

hg38 • Region Span ~157.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

colobomaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0001476

Submitter: Ambry Genetics

complex neurodevelopmental disorder with or without congenital anomaliesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100465

Submitter: PanelApp Australia

complex neurodevelopmental disorder with or without congenital anomaliesDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0100465

Submitter: ClinGen

The *MYH10* gene is located on chromosome 17 at 17p13.1 and encodes myosin heavy chain 10, a member of the conventional non-muscle myosin family that plays a role in cytokinesis, cell shape and other specialized functions. *MYH10* was first reported in relation to an autosomal dominant complex neurodevelopmental disorder with or without congenital anomalies in 2013 (Tuzovic et al., PMID: 25003005). AD complex neurodevelopmental disorder with or without congenital anomalies is characterized by delayed language and motor development, abnormalities of the corpus callosum, cardiac malformations, and gastrointestinal defects. Seventeen variants (missense, nonsense, and frameshift) that have been reported in 19 probands across 4 publications are included in this curation (PMIDs: 25003005, 25356899, 30712878, 35980381). More evidence is available in the literature, but the maximum score for genetic evidence (12 pts) has been reached.The mechanism of pathogenicity is reported to include both loss of function and dominant negative. This gene-disease relationship is further supported by multiple mouse models and in vitro functional assays (PMIDs: 9356462, 15034141, 35980381). In summary, there is definitive evidence supporting the relationship between *MYH10* and autosomal dominant complex neurodevelopmental disorder with or without congenital anomalies. 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 GCEP on the meeting date June 21, 2024 (SOP Version 10).

MYH10-related neurodevelopmental disorder with congenital anomaliesMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700281

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYH10 variants in ClinVar

23 Conditions Cataloged

not providedTotal: 173

Inborn genetic diseasesTotal: 167

not specifiedTotal: 54

MYH10-related disorderTotal: 47

Complex neurodevelopmental disorder with or without congenital anomaliesTotal: 6

See casesTotal: 4

Jaw-winking syndromeTotal: 3

Congenital fibrosis of extraocular musclesTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001256012.3. 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			1 clinvar	37 clinvar	5 clinvar	43
missense	3 clinvar	6 clinvar	302 clinvar	9 clinvar	2 clinvar	322
nonsense	3 clinvar	3 clinvar	8 clinvar			14
start loss			1 clinvar			1
frameshift	1 clinvar	2 clinvar	9 clinvar			12
splice donor/acceptor (+/-2bp)		2 clinvar	14 clinvar			16
Total	7	13	335	46	7	408

Highest pathogenic variant AF is 6.8428284e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 89 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001256012.3	RefSeq	NP_001242941.1	42	MANE Select
ENST00000360416.8	Ensembl	ENSP00000353590.4	42	MANE Select
NM_001256095.2	RefSeq	NP_001243024.1	41	Standard
NM_001375266.1	RefSeq	NP_001362195.1	41	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
myh10	Danio rerio	Structure: post-vent region Quality: curved abnormal

Gene / Model

Organism

Observed Phenotype

myh10

Danio rerio

Structure: post-vent region

Quality: curved

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Salmonella infection - Homo sapiens (human)
Tight junction - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Regulation of Actin Cytoskeleton
Developmental Biology

Biological Process

mitotic cytokinesis
in utero embryonic development
neuron migration
plasma membrane repair
cardiac septum development

Molecular Function

microfilament motor activity
actin binding
protein binding
calmodulin binding
ATP binding

Cellular Component

stress fiber
nucleus
cytoplasm
spindle
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360416
Coding exons: 42
Length: 156557
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125748
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	5.01	671	1.15e+3	0.584	0.0000717	13235
Missense (PolyPhen)		256	531.13	0.48199		6267
Synonymous	1.19	408	440	0.928	0.0000272	3701
Loss of Function	8.96	12	116	0.103	0.00000629	1366

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000034	0.000029	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the central part but not the margins of spreading cells), and lamellipodial extension; this function is mechanically antagonized by MYH9. {ECO:0000269|PubMed:20052411, ECO:0000269|PubMed:20603131}.;
Disease: DISEASE: Note=Associated with severe intellectual disability, microcephaly, and feeding difficulties as well as cerebral atrophy. {ECO:0000269|PubMed:25003005, ECO:0000269|PubMed:25356899}.;

Intolerance Scores

RVIS EVS: -2.08
RVIS percentile EVS: 1.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.946

Gene Damage Prediction

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