UPK1A
protein-codinguroplakin 1A, the group of Tetraspanins
Gene summary
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is found in the asymmetrical unit membrane (AUM) where it can complex with other transmembrane 4 superfamily proteins. It may play a role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells or in stabilizing the apical membrane through AUM/cytoskeletal interactions. The protein may also play a role in tumor suppression. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.0 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 UPK1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007000.4. 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 | 0 | |||||
| missense | 59 | 1 | 60 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 60 | 1 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008931.1 | 7 | MANE Select | |
| Ensembl | ENSP00000222275.2 | 7 | MANE Select | |
| RefSeq | NP_001268372.1 | 7 | Standard | |
| Ensembl | ENSP00000368298.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell surface receptor signaling pathway
- epithelial cell differentiation
- protein complex oligomerization
Molecular Function
- protein binding
- protein homodimerization activity
Cellular Component
- endoplasmic reticulum
- plasma membrane
- integral component of plasma membrane
- cell surface
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000222275
- Coding exons
- 7
- Length
- 11653
- Individuals with no LoFs
- 125674
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 73
- Defined
- 125748
- p
- 0.000294
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0531 | 176 | 174 | 1.01 | 0.0000106 | 1673 |
| Missense (PolyPhen) | 53 | 57.664 | 0.91912 | 569 | ||
| Synonymous | 0.358 | 66 | 69.8 | 0.946 | 0.00000467 | 517 |
| Loss of Function | -0.254 | 15 | 14.0 | 1.07 | 6.07e-7 | 144 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.0013 | 0.0013 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells or in stabilizing the apical membrane through AUM/cytoskeletal interactions (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0946
Intolerance Scores
- LoFtool
- 0.506
- RVIS EVS
- 0.93
- RVIS percentile EVS
- 89.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.586
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |