UNC45A

Chr 15

unc-45 myosin chaperone A

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

NCBI Gene: 55898 ENSG00000140553 UniProt: Q9H3U1

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

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtOsteootohepatoenteric syndrome

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.74

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 3.00

OE 0.53 (0.39–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.19Z-score

OE missense 0.98 (0.91–1.05)

562 obs / 575.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.39–0.74)

0≤0.351.4

Missense OE?0.98 (0.91–1.05)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 25 / 47.2Missense obs/exp: 562 / 575.0Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in UNC45A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 28

1,403 rare PASS variants

Rare truncating (LoF)

1 in 580

190 rare PASS variants

Rare synonymous (reference)

1 in 53

574 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UNC45A. 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 43	1 in 550
South Asian	~43k	1 in 29	1 in 730
Remaining (unassigned)	~30k	1 in 28	1 in 490
European (Finnish)	~27k	1 in 100	1 in 930
Admixed American	~22k	1 in 29	1 in 350
African / African American	~21k	1 in 29	1 in 600
East Asian	~20k	1 in 40	1 in 740
Ashkenazi Jewish	~13k	1 in 150	1 in 1,300
Middle Eastern	~2,884	1 in 33	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 20 coding exons well covered in gnomAD exomes and genomes.? see exons ↓