UNC45A

Chr 15

unc-45 myosin chaperone A

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

The protein acts as a co-chaperone for HSP90 and is necessary for normal cell proliferation, myotube formation, and myosin accumulation during muscle cell development. Mutations cause osteootohepatoenteric syndrome, a multisystem disorder affecting bone, ear, liver, and gastrointestinal systems, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein disruption.

ResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismLOEUF 0.74
Clinical SummaryUNC45A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 281 VUS of 598 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.000
Z-score 3.00
OE 0.53 (0.390.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.19Z-score
OE missense 0.98 (0.911.05)
562 obs / 575.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.390.74)
00.351.4
Missense OE0.98 (0.911.05)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 25 / 47.2Missense obs/exp: 562 / 575.0Syn Z: -0.30
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongUNC45A-related osteootohepatoenteric syndromeOTHERAR

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

DN
0.74top 25%
GOF
0.72top 25%
LOF
0.2874th %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

598 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic7
VUS281
Likely Benign236
Benign21
Conflicting5
20
Pathogenic
7
Likely Pathogenic
281
VUS
236
Likely Benign
21
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
5
12
0
20
Likely Pathogenic
5
0
2
0
7
VUS
13
249
19
0
281
Likely Benign
2
6
90
138
236
Benign
0
4
8
9
21
Conflicting
5
Total23264131147570

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC