UACA
protein-codinguveal autoantigen with coiled-coil domains and ankyrin repeats, the group of Ankyrin repeat domain containing
Gene summary
This gene encodes a protein that contains ankyrin repeats and coiled coil domains and likely plays a role in apoptosis. Studies in rodents have implicated the encoded protein in the stimulation of apoptosis and the regulation of mammary gland involution, in which the mammary gland returns to its pre-pregnant state. This protein has also been proposed to negatively regulate apoptosis based on experiments in human cell lines in which the protein was shown to interact with PRKC apoptosis WT1 regulator protein, also known as PAR-4, and inhibit translocation of the PAR-4 receptor. Autoantibodies to this protein have been identified in human patients with panuveitis and Graves' disease. Differential expression of this gene has been observed in various human cancers. [provided by RefSeq, May 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~109.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UACA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018003.4. 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 | 1 | 10 | 5 | 16 | ||
| missense | 186 | 10 | 8 | 204 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 194 | 20 | 13 | 227 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060473.2 | 19 | MANE Select | |
| Ensembl | ENSP00000314556.6 | 19 | MANE Select | |
| RefSeq | NP_001008225.1 | 19 | Standard | |
| Ensembl | ENSP00000369319.2 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- biological_process
- apoptotic signaling pathway
- regulation of NIK/NF-kappaB signaling
Molecular Function
- molecular_function
- protein binding
Cellular Component
- extracellular region
- nucleus
- cytosol
- cytoskeleton
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000322954
- Coding exons
- 19
- Length
- 109040
- Individuals with no LoFs
- 125490
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 256
- Defined
- 125747
- p
- 0.00102
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.471 | 641 | 675 | 0.949 | 0.0000318 | 9405 |
| Missense (PolyPhen) | 191 | 210.23 | 0.90854 | 2872 | ||
| Synonymous | -0.136 | 255 | 252 | 1.01 | 0.0000128 | 2460 |
| Loss of Function | 1.74 | 53 | 68.5 | 0.774 | 0.00000365 | 934 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.0010 | 0.00093 | notable |
| Ashkenazi Jewish | 0.00082 | 0.00079 | rare |
| East Asian | 0.00041 | 0.00038 | rare |
| Finnish | 0.0026 | 0.0026 | notable |
| European (Non-Finnish) | 0.00099 | 0.00097 | rare |
| South Asian | 0.00094 | 0.00088 | rare |
| Other | 0.0015 | 0.0015 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulates APAF1 expression and plays an important role in the regulation of stress-induced apoptosis. Promotes apoptosis by regulating three pathways, apoptosome up-regulation, LGALS3/galectin-3 down-regulation and NF-kappa-B inactivation. Regulates the redistribution of APAF1 into the nucleus after proapoptotic stress. Down-regulates the expression of LGALS3 by inhibiting NFKB1 (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.992
- RVIS EVS
- -0.52
- RVIS percentile EVS
- 20.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.182
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |