MYH14

myosin heavy chain 14, the group of Myosin heavy chains, class II

Basic information

Region (hg38): 19:50188186-50310542

Previous symbols: [ "DFNA4" ]

Links

ENSG00000105357

∙ NCBI:79784 ∙ OMIM:608568 ∙ HGNC:23212 ∙ Uniprot:Q7Z406 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal dominant nonsyndromic hearing loss 4A (Strong), mode of inheritance: AD
autosomal dominant nonsyndromic hearing loss 4A (Definitive), mode of inheritance: AD
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (Moderate), mode of inheritance: AD
autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (Supportive), mode of inheritance: AD
autosomal dominant nonsyndromic hearing loss 4A (Strong), mode of inheritance: AD
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (Strong), mode of inheritance: AD
nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 4A; Deafness, autosomal dominant 4B; Peripheral neuropathy, myopathy, hoarseness, and hearing loss	AD	General	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	Audiologic/Otolaryngologic; Musculoskeletal; Neurologic	7655461; 11938438; 15015131; 16222661; 21480433; 21368133
The onset of deafness has been described as postlingual

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYH14 gene.

not_provided (957 variants)
Inborn_genetic_diseases (249 variants)
not_specified (220 variants)
Autosomal_dominant_nonsyndromic_hearing_loss_4A (218 variants)
MYH14-related_disorder (82 variants)
Peripheral_neuropathy-myopathy-hoarseness-hearing_loss_syndrome (55 variants)
Hearing_impairment (8 variants)
Meniere_disease (6 variants)
Nonsyndromic_Hearing_Loss,_Dominant (4 variants)
Autosomal_dominant_nonsyndromic_hearing_loss (2 variants)
See_cases (2 variants)
Nonsyndromic_genetic_hearing_loss (2 variants)
Progressive_sensorineural_hearing_impairment (1 variants)
Peripheral_neuropathy (1 variants)
Peripheral_axonal_neuropathy (1 variants)
Impaired_vibration_sensation_in_the_lower_limbs (1 variants)
Primary_dilated_cardiomyopathy (1 variants)
VATER_association (1 variants)
Motor_polyneuropathy (1 variants)
EMG:_axonal_abnormality (1 variants)
EMG_abnormality (1 variants)
Sensorineural_hearing_loss_disorder (1 variants)
Charcot-Marie-Tooth_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYH14 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001145809.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			32 clinvar	202 clinvar	15 clinvar	249
missense	2 clinvar	8 clinvar	671 clinvar	85 clinvar	11 clinvar	777
nonsense	5 clinvar		4 clinvar			9
start loss						0
frameshift	7 clinvar	4 clinvar	6 clinvar	2 clinvar		19
splice donor/acceptor (+/-2bp)		5 clinvar	6 clinvar			11
Total	14	17	719	289	26

Highest pathogenic variant AF is 0.00003592461

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYH14	protein_coding	protein_coding	ENST00000601313	42	122360

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0422	0.958	125714	0	33	125747	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	1069	1.30e+3	0.822	0.0000951	12845
Missense in Polyphen		381	501.56	0.75963		4787
Synonymous	1.87	476	531	0.897	0.0000352	4160
Loss of Function	7.46	27	112	0.241	0.00000620	1204

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000159	0.000152
Ashkenazi Jewish	0.000305	0.000298
East Asian	0.000171	0.000163
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000181	0.000176
Middle Eastern	0.000171	0.000163
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. {ECO:0000250}.;
Disease: DISEASE: Deafness, autosomal dominant, 4A (DFNA4A) [MIM:600652]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:15015131, ECO:0000269|PubMed:16222661}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peripheral neuropathy, myopathy, hoarseness, and hearing loss (PNMHH) [MIM:614369]: A complex phenotype of progressive peripheral neuropathy and distal myopathy, with later onset of hoarseness and hearing loss. Affected individuals develop distal muscle weakness at a mean age of 10.6 years, followed by progressive atrophy of these muscles. The lower limbs are more severely affected than the upper limbs, and the muscle weakness first affects anterior leg muscles and later posterior leg muscles. {ECO:0000269|PubMed:21480433}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Salmonella infection - Homo sapiens (human);Tight junction - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Developmental Biology;Signal Transduction;EPH-Ephrin signaling;EPHA-mediated growth cone collapse;RHO GTPases Activate ROCKs;RHO GTPases activate PAKs;RHO GTPases activate PKNs;RHO GTPases activate CIT;RHO GTPase Effectors;Signaling by Rho GTPases;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;Semaphorin interactions;Axon guidance (Consensus)

Recessive Scores

pRec: 0.145

Intolerance Scores

loftool: 0.0292
rvis_EVS: -2.24
rvis_percentile_EVS: 1.31

Haploinsufficiency Scores

pHI: 0.225
hipred: Y
hipred_score: 0.595
ghis: 0.606

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.428

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Myh14
Phenotype: neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; muscle phenotype; cellular phenotype;

Gene ontology

Biological process: skeletal muscle contraction;skeletal muscle tissue development;sensory perception of sound;regulation of cell shape;neuronal action potential;actin filament-based movement;actomyosin structure organization;mitochondrion morphogenesis;vocalization behavior
Cellular component: stress fiber;cytosol;brush border;membrane;myosin II complex;growth cone;actomyosin;myelin sheath;extracellular exosome;myosin II filament
Molecular function: microfilament motor activity;calmodulin binding;ATP binding;ATPase activity;actin-dependent ATPase activity;actin filament binding