MYO5B

protein-coding

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

Gene summary

The protein encoded by this gene, together with other proteins, may be involved in plasma membrane recycling. Mutations in this gene are associated with microvillous inclusion disease. [provided by RefSeq, Sep 2009]

MANE transcript

NM_001080467.3

Inheritance

ClinVar variants

P:124U:720B:471

Top phenotype

Diarrhea 2, with microvillus atrophy, with or without cholestasis; Cholestasis, progressive familial intrahepatic 10

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr18:49,822,789-50,195,164

External References & Databases

Ensembl (ENSG00000167306)

Transcript & Mutation Effects

hg38 • Region Span ~372.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

digestive system disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0004335

Submitter: PanelApp Australia

microvillus inclusion diseaseSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009635

Submitter: Orphanet

microvillus inclusion diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009635

Submitter: Labcorp Genetics (formerly Invitae)

microvillus inclusion diseaseDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009635

Submitter: G2P

progressive familial intrahepatic cholestasis type 1SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008892

Submitter: Orphanet

cholestasis, progressive familial intrahepatic, 10STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030810

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Diarrhea 2, with microvillus atrophy, with or without cholestasis; Cholestasis, progressive familial intrahepatic 10AR

Manifestation: Gastrointestinal; Renal

Intervention: Gastrointestinal; Renal

Rationale: 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

Refs: 16800870; 19006234; 18724368; 21199752; 20186687; 22030065; 21206382; 22441677; 27532546; 28027573; 32304554; 33525641

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYO5B variants in ClinVar

9 Conditions Cataloged

not providedTotal: 1328

MYO5B-related disorderTotal: 345

Inborn genetic diseasesTotal: 279

Congenital microvillous atrophyTotal: 212

not specifiedTotal: 93

Cholestasis, progressive familial intrahepatic, 10Total: 47

DIARRHEA 2, WITH MICROVILLUS ATROPHY AND CHOLESTASISTotal: 4

Inflammatory bowel disease 1Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080467.3. 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			10 clinvar	413 clinvar	8 clinvar	431
missense	10 clinvar	21 clinvar	696 clinvar	41 clinvar	9 clinvar	777
nonsense	21 clinvar	8 clinvar	1 clinvar			30
start loss						0
frameshift	26 clinvar	12 clinvar	1 clinvar			39
splice donor/acceptor (+/-2bp)	8 clinvar	18 clinvar	12 clinvar			38
Total	65	59	720	454	17	1315

Highest pathogenic variant AF is 0.000029752313

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080467.3	RefSeq	NP_001073936.1	40	MANE Select
ENST00000285039.12	Ensembl	ENSP00000285039.6	40	MANE Select
ENST00000324581.10	Ensembl	ENSP00000315531.7	19	Standard
ENST00000592688.1	Ensembl	ENSP00000466368.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
myo5b	Danio rerio	Structure: enterocyte Quality: columnar abnormal

Gene / Model

Organism

Observed Phenotype

myo5b

Danio rerio

Structure: enterocyte

Quality: columnar

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

renal water homeostasis
protein transport
vesicle-mediated transport
endosomal transport

Molecular Function

microfilament motor activity
protein binding
calmodulin binding
ATP binding
Rab GTPase binding

Cellular Component

myosin complex
cytoplasmic vesicle membrane
protein-containing complex
apical cortex
recycling endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000285039
Coding exons: 40
Length: 372281
Individuals with no LoFs: 124735
Homozygous LoFs: 0
Heterozygous LoFs: 112
Defined: 124847
p: 0.000449

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.616	1051	996	1.05	0.0000645	12201
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00084	0.00084	rare
Latino/Admixed American	0.00030	0.00029	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.0011	0.0011	notable
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00036	0.00036	rare
South Asian	0.00056	0.00056	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.668

Gene Damage Prediction

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