UPK2

Chr 11

uroplakin 2

Also known as: UP2, UPII

NCBI Gene: 7379 ENSG00000110375 UniProt: O00526 OMIM: 611558

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.90

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.90LOEUF

pLI 0.000

Z-score -0.92

OE 1.37 (0.82–1.90)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.24Z-score

OE missense 1.06 (0.92–1.24)

118 obs / 111.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.37 (0.82–1.90)

0≤0.351.4

Missense OE?1.06 (0.92–1.24)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 10 / 7.3Missense obs/exp: 118 / 111.0Syn Z: -0.19

Background carrier burden — how many people carry a rare variant somewhere in UPK2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

244 rare PASS variants

Rare truncating (LoF)

1 in 490

53 rare PASS variants

Rare synonymous (reference)

1 in 350

105 rare PASS variants

Rare missense and truncating variants are carried at similar rates in UPK2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 500
South Asian	~43k	1 in 180	1 in 5,400
Remaining (unassigned)	~30k	1 in 110	1 in 440
European (Finnish)	~27k	1 in 790	1 in 3,200
Admixed American	~22k	1 in 150	1 in 720
African / African American	~21k	1 in 110	1 in 890
East Asian	~20k	1 in 190	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 1,300	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 170	1 in 260

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓