MYO5B

myosin VB, the group of Myosin heavy chains, class V|MicroRNA protein coding host genes

Basic information

Region (hg38): 18:49822788-50195164

Links

ENSG00000167306 ∙ NCBI:4645 ∙ OMIM:606540 ∙ HGNC:7603 ∙ Uniprot:Q9ULV0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microvillus inclusion disease (Definitive), mode of inheritance: AR
• microvillus inclusion disease (Strong), mode of inheritance: AR
• microvillus inclusion disease (Supportive), mode of inheritance: AR
• progressive familial intrahepatic cholestasis type 1 (Supportive), mode of inheritance: AR
• microvillus inclusion disease (Strong), mode of inheritance: AR
• cholestasis, progressive familial intrahepatic, 10 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diarrhea 2, with microvillus atrophy, with or without cholestasis; Cholestasis, progressive familial intrahepatic 10	AR	Gastrointestinal; Renal	Individuals with Diarrhea 2, with microvillus atrophy, with or without cholestasis may require nutritional support with parenteral nutrition; Renal fanconi syndrome has been described, and appropriate care of related sequelae may be beneficial; Individuals with progressive familial intrahepatic cholestasis 10 or with cholestasis as part of Diarrhea 2, with microvillus atrophy. with or without cholestasis may benefit from medical management (eg, with ursodeoxycholic acid), but may require surgical intervention (eg, with biliary diversion); Liver transplant has been described	Gastrointestinal; Renal	16800870; 19006234; 18724368; 21199752; 20186687; 22030065; 21206382; 22441677; 27532546; 28027573; 32304554; 33525641

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYO5B gene.

• not provided (1052 variants)
• Congenital microvillous atrophy (348 variants)
• Inborn genetic diseases (76 variants)
• Diarrhea with Microvillus Atrophy (18 variants)
• not specified (16 variants)
• MYO5B-related condition (13 variants)
• Congenital microvillous atrophy;Cholestasis, progressive familial intrahepatic, 10 (6 variants)
• Cholestasis, progressive familial intrahepatic, 10 (5 variants)
• Cholestasis, progressive familial intrahepatic, 10;Congenital microvillous atrophy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYO5B 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			11	211	15	237
missense	2	4	465	19	17	507
nonsense	16	1	2			19
start loss						0
frameshift	10	3				13
inframe indel			5		1	6
splice donor/acceptor (+/-2bp)	1	5	1			7
splice region		1	28	27	3	59
non coding			153	118	145	416
Total	29	13	637	348	178

Highest pathogenic variant AF is 0.0000263

Variants in MYO5B

This is a list of pathogenic ClinVar variants found in the MYO5B region.

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

Position	Type	Phenotype	Significance	ClinVar
18-49822831-T-C		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)
18-49822927-G-A		Congenital microvillous atrophy	Uncertain significance (Mar 30, 2018)
18-49823043-A-G		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823048-C-A		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)
18-49823080-T-C		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823090-C-G		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)
18-49823092-T-G		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823103-C-G		Congenital microvillous atrophy	Benign (Jan 13, 2018)
18-49823106-A-G		Congenital microvillous atrophy	Uncertain significance (Jan 15, 2018)
18-49823107-T-C		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823114-C-T		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823120-T-G		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)
18-49823129-G-C		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)
18-49823130-A-G		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823132-A-ACTTT		Diarrhea with Microvillus Atrophy	Uncertain significance (Jun 14, 2016)
18-49823154-G-A		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)
18-49823156-A-G		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823171-T-C		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)
18-49823176-A-AT		Diarrhea with Microvillus Atrophy	Uncertain significance (Jun 14, 2016)
18-49823179-A-G		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823189-C-T		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823198-C-G		Congenital microvillous atrophy	Uncertain significance (Jan 12, 2018)
18-49823198-C-T		Congenital microvillous atrophy	Benign (Jan 12, 2018)
18-49823232-T-C		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)
18-49823251-G-A		Congenital microvillous atrophy	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYO5B	protein_coding	protein_coding	ENST00000285039	40	372281

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.38e-23	1.00	124735	0	112	124847	0.000449

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.616	1051	996	1.05	0.0000645	12201
Missense in Polyphen		353	385.14	0.91655		4693
Synonymous	-1.68	440	397	1.11	0.0000253	3415
Loss of Function	4.13	53	96.9	0.547	0.00000483	1186

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00114	0.00113
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.00111	0.00106
Finnish	0.000233	0.000232
European (Non-Finnish)	0.000362	0.000362
Middle Eastern	0.00111	0.00106
South Asian	0.000556	0.000556
Other	0.000495	0.000494

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. Required in a complex with RAB11A and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Together with RAB11A participates in CFTR trafficking to the plasma membrane and TF (transferrin) recycling in nonpolarized cells. Together with RAB11A and RAB8A participates in epithelial cell polarization. Together with RAB25 regulates transcytosis. {ECO:0000269|PubMed:21206382, ECO:0000269|PubMed:21282656}.
• Disease: DISEASE: Diarrhea 2, with microvillus atrophy (DIAR2) [MIM:251850]: A disease characterized by onset of intractable life-threatening watery diarrhea during infancy. Two forms are recognized: early-onset microvillus inclusion disease with diarrhea beginning in the neonatal period, and late-onset, with first symptoms appearing after 3 or 4 months of life. {ECO:0000269|PubMed:18724368, ECO:0000269|PubMed:19006234, ECO:0000269|PubMed:20186687, ECO:0000269|PubMed:21206382, ECO:0000269|PubMed:24138727, ECO:0000269|PubMed:24892806}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.180

Intolerance Scores

• loftool: 0.0862
• rvis_EVS: -0.37
• rvis_percentile_EVS: 28.21

Haploinsufficiency Scores

• pHI: 0.247
• hipred: Y
• hipred_score: 0.706
• ghis: 0.501

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.668

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myo5b
• Phenotype: homeostasis/metabolism 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); 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); growth/size/body region phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: myo5b
• Affected structure: enterocyte
• Phenotype tag: abnormal
• Phenotype quality: columnar

Gene ontology

• Biological process: renal water homeostasis;protein transport;vesicle-mediated transport;endosomal transport
• Cellular component: myosin complex;cytoplasmic vesicle membrane;protein-containing complex;apical cortex;recycling endosome;extracellular exosome
• Molecular function: microfilament motor activity;protein binding;calmodulin binding;ATP binding;Rab GTPase binding;actin filament binding