UNC45A
protein-codingunc-45 myosin chaperone A, the group of Armadillo like helical domain containing
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~23.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859164
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0859164
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0859164
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Gastrointestinal; Musculoskeletal
Intervention: Audiologic/Otolaryngologic; Gastrointestinal
Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition may include intractable secretory diarrhea. which may require parenteral nutrition
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UNC45A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018671.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 191 | 10 | 203 | ||
| missense | 4 | 1 | 328 | 14 | 4 | 351 |
| nonsense | 2 | 12 | 14 | |||
| start loss | 0 | |||||
| frameshift | 1 | 3 | 5 | 9 | ||
| splice donor/acceptor (+/-2bp) | 5 | 11 | 1 | 17 | ||
| Total | 7 | 9 | 358 | 206 | 14 | 594 |
Highest pathogenic variant AF is 0.000028498642
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061141.2 | 20 | MANE Select | |
| Ensembl | ENSP00000407487.2 | 20 | MANE Select | |
| RefSeq | NP_001034764.1 | 20 | Standard | |
| RefSeq | NP_001310548.1 | 20 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| unc45a | Danio rerio | Structure: primary head sinus Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- muscle organ development
- cell differentiation
- chaperone-mediated protein folding
Molecular Function
- protein binding
- cadherin binding
- Hsp90 protein binding
Cellular Component
- Golgi apparatus
- cytosol
- nuclear speck
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000418476
- Coding exons
- 20
- Length
- 23914
- Individuals with no LoFs
- 125397
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 350
- Defined
- 125748
- p
- 0.00140
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.192 | 562 | 575 | 0.977 | 0.0000347 | 6082 |
| Missense (PolyPhen) | 181 | 188.73 | 0.95904 | 1916 | ||
| Synonymous | -0.296 | 248 | 242 | 1.02 | 0.0000148 | 1952 |
| Loss of Function | 3.00 | 25 | 47.2 | 0.529 | 0.00000259 | 517 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00081 | 0.00074 | rare |
| Latino/Admixed American | 0.0010 | 0.0010 | notable |
| Ashkenazi Jewish | 0.0060 | 0.0060 | notable |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00032 | 0.00032 | rare |
| European (Non-Finnish) | 0.0019 | 0.0018 | notable |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as co-chaperone for HSP90. Prevents the stimulation of HSP90AB1 ATPase activity by AHSA1. Positive factor in promoting PGR function in the cell. May be necessary for proper folding of myosin (Potential). Necessary for normal cell proliferation. Necessary for normal myotube formation and myosin accumulation during muscle cell development. May play a role in erythropoiesis in stroma cells in the spleen (By similarity). {ECO:0000250, ECO:0000269|PubMed:12119110, ECO:0000269|PubMed:16478993, ECO:0000305}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.891
- RVIS EVS
- -1.1
- RVIS percentile EVS
- 6.95
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.913
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |