UNC45A

Chr 15AR

unc-45 myosin chaperone A

Also known as: GC-UNC45, GCUNC-45, GCUNC45, IRO039700, OOHE, SMAP-1, SMAP1, UNC-45A

NCBI Gene: 55898ENSG00000140553UniProt: Q9H3U1

This gene encodes a regulatory component of the progesterone receptor/heat shock protein 90 chaperoning complex, which functions in the assembly and folding of the progesterone receptor. The encoded protein is thought to be essential for normal cell proliferation, and for the accumulation of myosin during development of muscle cells. [provided by RefSeq, Sep 2018]

Primary Disease Associations & Inheritance

Osteootohepatoenteric syndromeMIM #619377
AR
570
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UNC45A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 318 VUS of 570 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.74LOEUF
pLI 0.000
Z-score 3.00
OE 0.53 (0.39–0.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.19Z-score
OE missense 0.98 (0.91–1.05)
562 obs / 575.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.53 (0.39–0.74)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 25 / 47.2Missense obs/exp: 562 / 575.0Syn Z: -0.30

ClinVar Variant Classifications

570 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic7
VUS318
Likely Benign228
Benign2
Conflicting6
9
Pathogenic
7
Likely Pathogenic
318
VUS
228
Likely Benign
2
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
3
5
0
9
Likely Pathogenic
5
0
2
0
7
VUS
7
283
27
1
318
Likely Benign
0
3
88
137
228
Benign
0
1
0
1
2
Conflicting
—6
Total13290122139570

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

View in ClinVar →

Protein Context — Lollipop Plot

UNC45A · protein map & ClinVar variants

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

Gene2Phenotype Curations

UNC45A-related osteootohepatoenteric syndrome

strong
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Osteootohepatoenteric syndrome

MIM #619377

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
UNC45A deficiency causes microvillus inclusion disease-like phenotype by impairing myosin VB-dependent apical trafficking.
Duclaux-Loras R et al.·J Clin Invest
2022
A Functional Relationship Between UNC45A and MYO5B Connects Two Rare Diseases With Shared Enteropathy.
Li Q et al.·Cell Mol Gastroenterol Hepatol
2022Functional
Uncovering the Relationship Between Genes and Phenotypes Beyond the Gut in Microvillus Inclusion Disease.
Sun M et al.·Cell Mol Gastroenterol Hepatol
2024Review
Altered chaperone-nonmuscle myosin II interactions drive pathogenicity of the UNC45A c.710T>C variant in osteo-oto-hepato-enteric syndrome.
Waich S et al.·JCI Insight
2025
A New Unc45a 5'utr Variant In Patients With Aagenaes Syndrome.
Tan TT et al.·Am J Med Genet A
2025Case report
UNC45A-related osteo-oto-hepato-enteric syndrome in a Chinese neonate.
Kong Y et al.·Eur J Med Genet
2023
Modeling the cell biology of monogenetic intestinal epithelial disorders.
Kaji I et al.·J Cell Biol
2024Review
A Case Report and Literature Review on Osteo-Oto-Hepato-Enteric Syndrome in Premature Infants Caused by UNC45A Deficiency.
Sun Z et al.·Mol Genet Genomic Med
2025Review
Aagenaes syndrome/lymphedema cholestasis syndrome 1 is caused by a founder variant in the 5'-untranslated region of UNC45A.
Almaas R et al.·J Hepatol
2023
Pain/Stress, Mitochondrial Dysfunction, and Neurodevelopment in Preterm Infants.
Zhao T et al.·Dev Neurosci
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools