UPK3A

Chr 22

uroplakin 3A

Also known as: UP3A, UPIII, UPIIIA, UPK3

NCBI Gene: 7380ENSG00000100373UniProt: O75631

This gene encodes a member of the uroplakin family, a group of transmembrane proteins that form complexes on the apical surface of the bladder epithelium. Mutations in this gene may be associated with renal adysplasia. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009]

178
ClinVar variants
70
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— UPK3A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
70 Pathogenic / Likely Pathogenic· 70 VUS of 178 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.78LOEUF
pLI 0.000
Z-score -0.61
OE 1.19 (0.78–1.78)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.41Z-score
OE missense 1.09 (0.96–1.23)
180 obs / 165.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.19 (0.78–1.78)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.09 (0.96–1.23)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 14 / 11.7Missense obs/exp: 180 / 165.2Syn Z: 0.56

ClinVar Variant Classifications

178 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68
Likely Pathogenic2
VUS70
Likely Benign17
Benign10
Conflicting2
68
Pathogenic
2
Likely Pathogenic
70
VUS
17
Likely Benign
10
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
68
0
68
Likely Pathogenic
1
0
1
0
2
VUS
1
56
10
3
70
Likely Benign
1
5
5
6
17
Benign
0
2
4
4
10
Conflicting
—2
Total3638813169

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

UPK3A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
UROPLAKIN 3A; UPK3A
MIM #611559 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
State of the Science for Kidney Disorders in Phelan-McDermid Syndrome: UPK3A, FBLN1, WNT7B, and CELSR1 as Candidate Genes.
McCoy MD et al.·Genes (Basel)
2022Review
Whole exome sequencing identifies KIF26B, LIFR and LAMC1 mutations in familial vesicoureteral reflux.
Bartik ZI et al.·PLoS One
2022
Genetics of kidney disorders in Phelan-McDermid syndrome: evidence from 357 registry participants.
McCoy MD et al.·Pediatr Nephrol
2024
Clinical and molecular characterization of an emerging chromosome 22q13.31 microdeletion syndrome.
Palumbo P et al.·Am J Med Genet A
2018Case report
Genes in the ureteric budding pathway: association study on vesico-ureteral reflux patients.
van Eerde AM et al.·PLoS One
2012Cohort
RPL29 as a radiotherapy-sensitive prognostic biomarker in multiple myeloma.
Wang Y et al.·World J Surg Oncol
2025
Uroplakin 3a(+) Cells Are a Distinctive Population of Epithelial Progenitors that Contribute to Airway Maintenance and Post-injury Repair.
Guha A et al.·Cell Rep
2017
Integrated analysis identifies a long non-coding RNAs-messenger RNAs signature for prediction of prognosis in hepatitis B virus-hepatocellular carcinoma patients.
Bai Z et al.·Medicine (Baltimore)
2020Cohort
Identification and validation of regulatory SNPs that modulate transcription factor chromatin binding and gene expression in prostate cancer.
Jin HJ et al.·Oncotarget
2016
Loss of the urothelial differentiation marker FOXA1 is associated with high grade, late stage bladder cancer and increased tumor proliferation.
DeGraff DJ et al.·PLoS One
2012Clinical trial
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools