MYO5B

Chr 18AR

myosin VB

Also known as: DIAR2, MVID1, PFIC10

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.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Cholestasis, progressive familial intrahepatic, 10MIM #619868
AR
Diarrhea 2, with microvillus atrophy, with or without cholestasisMIM #251850
AR
1
Active trials
27
Pubs (1 yr)
48
P/LP submissions
17%
P/LP missense
0.69
LOEUF
LOF
Mechanism· G2P
Clinical SummaryMYO5B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 175 VUS of 500 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — MYO5B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 4.13
OE 0.55 (0.440.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.62Z-score
OE missense 1.05 (1.001.11)
1051 obs / 996.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.55 (0.440.69)
00.351.4
Missense OE1.05 (1.001.11)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 53 / 96.9Missense obs/exp: 1051 / 996.3Syn Z: -1.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMYO5B-related microvillus inclusion diseaseLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7327th %ile
GOF
0.6638th %ile
LOF
0.2775th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic19
VUS175
Likely Benign240
Benign3
Conflicting1
27
Pathogenic
19
Likely Pathogenic
175
VUS
240
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
10
0
27
Likely Pathogenic
10
7
2
0
19
VUS
0
166
7
2
175
Likely Benign
0
3
101
136
240
Benign
0
0
2
1
3
Conflicting
1
Total26177122139465

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MYO5B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC