MYO5A

myosin VA, the group of Myosin heavy chains, class V

Basic information

Region (hg38): 15:52307281-52529132

Previous symbols: [ "MYH12" ]

Links

ENSG00000197535 ∙ NCBI:4644 ∙ OMIM:160777 ∙ HGNC:7602 ∙ Uniprot:Q9Y4I1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Griscelli syndrome type 3 (Definitive), mode of inheritance: AR
• Griscelli syndrome type 1 (Moderate), mode of inheritance: AR
• Griscelli syndrome type 3 (Supportive), mode of inheritance: AR
• Griscelli syndrome type 1 (Strong), mode of inheritance: AR
• Griscelli syndrome type 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Griscelli syndrome, type 1	AR	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	Dermatologic; Neurologic	9207796; 10704277; 12452176

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYO5A gene.

• Griscelli syndrome type 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYO5A gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	53	13	68
missense			104	7	4	115
nonsense		1	1			2
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)	1		1			2
splice region			4	17	3	24
non coding				27	101	128
Total	1	2	108	87	118

Variants in MYO5A

This is a list of pathogenic ClinVar variants found in the MYO5A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-52313664-A-G			Benign (Jun 20, 2021)
15-52313693-C-G		not specified	Likely benign (Jun 27, 2016)
15-52313703-C-G		Inborn genetic diseases	Uncertain significance (May 27, 2021)
15-52313720-G-A		not specified	Uncertain significance (Feb 04, 2015)
15-52313727-C-G		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
15-52313728-T-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
15-52313744-G-C			Benign (Jun 04, 2023)
15-52313755-C-T			Uncertain significance (Oct 17, 2022)
15-52313765-T-C			Likely benign (Jul 01, 2024)
15-52313816-C-G		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
15-52313839-G-A			Uncertain significance (Mar 29, 2022)
15-52313844-C-T		Inborn genetic diseases	Uncertain significance (Jun 02, 2024)
15-52313863-A-G			Benign (Dec 03, 2021)
15-52314106-A-T			Likely benign (Jul 15, 2022)
15-52314142-G-A		MYO5A-related disorder	Benign (Aug 28, 2018)
15-52317032-G-A		not specified	Benign/Likely benign (Jan 24, 2024)
15-52317044-C-T		not specified • Inborn genetic diseases • Griscelli syndrome type 1	Benign/Likely benign (Aug 01, 2024)
15-52317084-G-A			Likely benign (Sep 14, 2021)
15-52317141-G-A			Likely benign (Dec 31, 2019)
15-52317228-A-G		Inborn genetic diseases	Uncertain significance (Dec 23, 2021)
15-52317229-A-G			Likely benign (Sep 19, 2022)
15-52319042-G-A			Likely benign (Jun 26, 2022)
15-52319048-G-A		not specified	Benign (Jan 09, 2024)
15-52319065-C-T			Likely benign (Jul 31, 2018)
15-52319127-C-A		Inborn genetic diseases	Uncertain significance (May 02, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYO5A	protein_coding	protein_coding	ENST00000399231	41	221768

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.944	0.0560	124765	0	36	124801	0.000144

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.10	723	998	0.724	0.0000584	12252
Missense in Polyphen		217	382.35	0.56754		4880
Synonymous	1.06	331	356	0.928	0.0000188	3412
Loss of Function	7.71	23	111	0.208	0.00000662	1278

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000191	0.000180
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000278	0.000278
Finnish	0.0000466	0.0000464
European (Non-Finnish)	0.000160	0.000159
Middle Eastern	0.000278	0.000278
South Asian	0.000131	0.000131
Other	0.000331	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. Involved in melanosome transport. Also mediates the transport of vesicles to the plasma membrane. May also be required for some polarization process involved in dendrite formation. {ECO:0000269|PubMed:10448864}.
• Disease: DISEASE: Griscelli syndrome 3 (GS3) [MIM:609227]: Rare autosomal recessive disorder characterized by pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes, without other clinical manifestations. {ECO:0000269|PubMed:12897212}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Elejalde syndrome (ELEJAS) [MIM:256710]: Autosomal recessive condition characterized by skin hypopigmentation, the presence of large clumps of pigment in hair shafts, silvery-gray hair, accumulation of melanosomes in melanocytes and primary neurological abnormalities. Elejalde syndrome may be the same entity as Griscelli syndrome type I. {ECO:0000269|PubMed:12058346}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Translocation of GLUT4 to the plasma membrane (Consensus)

Recessive Scores

• pRec: 0.388

Intolerance Scores

• loftool: 0.143
• rvis_EVS: -1.41
• rvis_percentile_EVS: 4.15

Haploinsufficiency Scores

• pHI: 0.524
• hipred: Y
• hipred_score: 0.648
• ghis: 0.615

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.797

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myo5a
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; craniofacial phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype

Gene ontology

• Biological process: exocytosis;post-Golgi vesicle-mediated transport;chemical synaptic transmission;visual perception;vesicle-mediated transport;actin filament-based movement;vesicle transport along actin filament;insulin secretion;melanocyte differentiation;regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity;locomotion involved in locomotory behavior;secretory granule localization;melanosome transport;cellular response to insulin stimulus;melanin biosynthetic process;odontogenesis;myelination;long-chain fatty acid biosynthetic process;hair follicle maturation;synapse organization;protein localization to plasma membrane;establishment of endoplasmic reticulum localization to postsynapse;regulation of postsynaptic cytosolic calcium ion concentration;regulation of Golgi organization
• Cellular component: ruffle;photoreceptor outer segment;cytoplasm;lysosome;early endosome;late endosome;peroxisome;endoplasmic reticulum;smooth endoplasmic reticulum;Golgi apparatus;cytosol;intermediate filament;actin filament;membrane;unconventional myosin complex;growth cone;vesicle;filopodium tip;insulin-responsive compartment;microtubule plus-end;melanosome;actomyosin;neuron projection;neuronal cell body;recycling endosome;extracellular exosome;postsynapse;glutamatergic synapse
• Molecular function: microfilament motor activity;RNA binding;calcium ion binding;protein binding;calmodulin binding;ATP binding;Rab GTPase binding;identical protein binding;actin filament binding;disordered domain specific binding