UPK2
protein-codinguroplakin 2
Gene summary
This gene encodes one of the proteins of the highly conserved urothelium-specific integral membrane proteins of the asymmetric unit membrane which forms urothelium apical plaques in mammals. The asymmetric unit membrane is believed to strengthen the urothelium by preventing cell rupture during bladder distention. The encoded protein is expressed in the peripheral blood of bladder cancer patients with transitional cell carcinomas.[provided by RefSeq, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.4 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 UPK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006760.4. 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 | 24 | 1 | 25 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | 2 | |||
| Total | 0 | 0 | 25 | 1 | 1 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006751.1 | 5 | MANE Select | |
| Ensembl | ENSP00000264031.2 | 5 | MANE Select | |
| Ensembl | ENSP00000769187.1 | 4 | Standard | |
| Ensembl | ENSP00000769188.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- multicellular organism development
- epithelial cell differentiation
Molecular Function
- protein binding
Cellular Component
- integral component of plasma membrane
- apical plasma membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264031
- Coding exons
- 5
- Length
- 33397
- Individuals with no LoFs
- 125295
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 448
- Defined
- 125746
- p
- 0.00179
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.237 | 118 | 111 | 1.06 | 0.00000622 | 1147 |
| Missense (PolyPhen) | 55 | 51.947 | 1.0588 | 528 | ||
| Synonymous | -0.187 | 48 | 46.4 | 1.03 | 0.00000232 | 439 |
| Loss of Function | -0.916 | 10 | 7.32 | 1.37 | 4.75e-7 | 75 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0028 | 0.0028 | notable |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.0031 | 0.0031 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0020 | 0.0020 | notable |
| South Asian | 0.0033 | 0.0032 | notable |
| Other | 0.00049 | 0.00049 | 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 regulating the assembly of the AUM (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.157
Intolerance Scores
- LoFtool
- 0.827
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 60.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.751
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |