MYO5B

Chr 18AR

myosin VB

Also known as: DIAR2, MVID1, PFIC10

NCBI Gene: 4645 ENSG00000167306 UniProt: Q9ULV0 OMIM: 606540

MYO5B encodes a motor protein that transports vesicles and is required for proper trafficking of proteins to the plasma membrane, including the bile salt export pump ABCB11 in hepatocytes and transferrin receptors in epithelial cells. Autosomal recessive mutations cause microvillous inclusion disease presenting with severe diarrhea and malabsorption in infancy, often accompanied by progressive familial intrahepatic cholestasis. The gene shows low constraint against loss-of-function variants (LOEUF 0.688), consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cholestasis, progressive familial intrahepatic, 10MIM #619868

Diarrhea 2, with microvillus atrophy, with or without cholestasisMIM #251850

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cholestasis, progressive familial intrahepatic; Diarrhea 2, with microvillus atrophy, with or without cholestasis; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.69

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — MYO5B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.69LOEUF

pLI 0.000

Z-score 4.13

OE 0.55 (0.44–0.69)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.62Z-score

OE missense 1.05 (1.00–1.11)

1051 obs / 996.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.55 (0.44–0.69)

0≤0.351.4

Missense OE?1.05 (1.00–1.11)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 53 / 96.9Missense obs/exp: 1051 / 996.3Syn Z: -1.68

Background carrier burden — how many people carry a rare variant somewhere in MYO5B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 20

2,466 rare PASS variants

Rare truncating (LoF)

1 in 740

278 rare PASS variants

Rare synonymous (reference)

1 in 54

977 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MYO5B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 26	1 in 760
South Asian	~43k	1 in 22	1 in 480
Remaining (unassigned)	~30k	1 in 18	1 in 510
European (Finnish)	~27k	1 in 88	1 in 1,200
Admixed American	~22k	1 in 23	1 in 1,100
African / African American	~21k	1 in 21	1 in 780
East Asian	~20k	1 in 27	1 in 530
Ashkenazi Jewish	~13k	1 in 94	1 in 1,900
Middle Eastern	~2,884	1 in 18	1 in 570

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 39 of 40 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 39 of 40 (exon 17 below).? see exons ↓