UPK1B

Summary

UPK1B (uroplakin 1B, HGNC:12578) is a protein-coding gene on chromosome 3q13.32, encoding Uroplakin-1b (O75841). Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells.

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 form a 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 use of alternate polyadenylation sites has been found for this gene.

Source: NCBI Gene 7348 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_006952

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12578
Approved symbol	UPK1B
Name	uroplakin 1B
Location	3q13.32
Locus type	gene with protein product
Status	Approved
Aliases	TSPAN20
Ensembl gene	ENSG00000114638
Ensembl biotype	protein_coding
OMIM	602380
Entrez	7348

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000264234, ENST00000460625, ENST00000479520, ENST00000494855, ENST00000497685, ENST00000863543, ENST00000863544, ENST00000863545, ENST00000863546

RefSeq mRNA: 1 — MANE Select: NM_006952 NM_006952

CCDS: CCDS2985

Canonical transcript exons

ENST00000264234 — 8 exons

Exon	Start	End
ENSE00000823592	119190245	119190319
ENSE00001012106	119190982	119191104
ENSE00001012107	119186714	119186810
ENSE00001012108	119199057	119199140
ENSE00001012110	119203917	119205143
ENSE00001012111	119194219	119194398
ENSE00001866550	119173598	119173638
ENSE00003572343	119187775	119187975

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 99.24.

FANTOM5 (CAGE): breadth broad, TPM avg 7.6861 / max 2948.0752, expressed in 239 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38076	7.2249	197
38074	0.1958	51
38075	0.1864	49
38077	0.0791	35

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.24	gold quality
epithelium of nasopharynx	UBERON:0001951	98.86	gold quality
nasopharynx	UBERON:0001728	98.85	gold quality
nasal cavity epithelium	UBERON:0005384	97.00	gold quality
amniotic fluid	UBERON:0000173	94.82	gold quality
parietal pleura	UBERON:0002400	91.72	gold quality
mucosa of urinary bladder	UBERON:0001259	91.39	gold quality
trachea	UBERON:0003126	89.49	gold quality
pancreatic ductal cell	CL:0002079	89.20	silver quality
germinal epithelium of ovary	UBERON:0001304	89.02	gold quality
nasal cavity mucosa	UBERON:0001826	88.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.00	gold quality
eye	UBERON:0000970	86.82	gold quality
urinary bladder	UBERON:0001255	86.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.88	gold quality
bronchus	UBERON:0002185	83.27	gold quality
epithelium of bronchus	UBERON:0002031	83.09	gold quality
pleura	UBERON:0000977	83.08	gold quality
nephron tubule	UBERON:0001231	81.33	gold quality
bronchial epithelial cell	CL:0002328	80.67	gold quality
epithelial cell of pancreas	CL:0000083	80.63	silver quality
gall bladder	UBERON:0002110	79.79	gold quality
pericardium	UBERON:0002407	78.66	gold quality
islet of Langerhans	UBERON:0000006	78.45	gold quality
pharyngeal mucosa	UBERON:0000355	78.33	gold quality
oral cavity	UBERON:0000167	78.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.06	gold quality
endometrium	UBERON:0001295	75.48	gold quality
renal glomerulus	UBERON:0000074	75.07	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	314.17
E-CURD-114	yes	70.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, SP1

miRNA regulators (miRDB)

62 targeting UPK1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-488-3P	99.61	68.79	1731

Literature-anchored findings (GeneRIF, showing 8)

• established the genomic organization of the UPIb gene (PMID:12031497)
• Loss of uroplakin Ib expression is associated with bladder carcinomas (PMID:15140401)
• Loss of uroplakin Ib expression by CpG methylation of Sp1/NFkappaB-binding motifs within the proximal promoter is associated with urothelial tumors (PMID:16354592)
• The biopsy-induced increase in the expression of UPIb and other genes encoding membrane proteins supports the possible importance of the membrane structure and stability during implantation. (PMID:18355812)
• Urine UPIb levels may be useful for predicting the risk of recurrent urinary tract infections in patients diagnosed with their first UTI and may also be considered as a noninvasive screening test for vesicoureteral reflux. (PMID:24559587)
• UPK1B is up-regulated in bladder cancer and is significantly correlated with tumor stage, lymph node metastasis and poor prognosis. (PMID:30229818)
• NAA10 promotes proliferation of renal cell carcinoma by upregulating UPK1B. (PMID:33275221)
• KRT13 and UPK1B for differential diagnosis between metastatic lung carcinoma from oral squamous cell carcinoma and lung squamous cell carcinoma. (PMID:38114532)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Upk1b	ENSMUSG00000049436
rattus_norvegicus	Upk1b	ENSRNOG00000027380

Paralogs (32): TSPAN6 (ENSG00000000003), CD9 (ENSG00000010278), TSPAN9 (ENSG00000011105), TSPAN17 (ENSG00000048140), TSPAN32 (ENSG00000064201), CD82 (ENSG00000085117), TSPAN15 (ENSG00000099282), CD37 (ENSG00000104894), UPK1A (ENSG00000105668), TSPAN12 (ENSG00000106025), TSPAN13 (ENSG00000106537), TSPAN14 (ENSG00000108219), CD81 (ENSG00000110651), TSPAN11 (ENSG00000110900), PRPH2 (ENSG00000112619), TSPAN1 (ENSG00000117472), TSPAN8 (ENSG00000127324), TSPAN16 (ENSG00000130167), TSPAN2 (ENSG00000134198), CD63 (ENSG00000135404), TSPAN31 (ENSG00000135452), TSPAN3 (ENSG00000140391), CD53 (ENSG00000143119), ROM1 (ENSG00000149489), TSPAN7 (ENSG00000156298), TSPAN18 (ENSG00000157570), TSPAN33 (ENSG00000158457), TSPAN5 (ENSG00000168785), CD151 (ENSG00000177697), TSPAN10 (ENSG00000182612), TSPAN4 (ENSG00000214063), TSPAN19 (ENSG00000231738)

Protein

Protein identifiers

Uroplakin-1b — O75841 (reviewed: O75841)

Alternative names: Tetraspanin-20, Uroplakin Ib

All UniProt accessions (5): C9J027, C9J6N2, C9J9M7, E7ETN9, O75841

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Heterodimer with uroplakin-3A (UPK3A) or uroplakin-3B (UPK3B).

Subcellular location. Membrane.

Tissue specificity. Bladder epithelium.

Post-translational modifications. N-glycosylated with high-mannose oligosaccharides.

Similarity. Belongs to the tetraspanin (TM4SF) family.

RefSeq proteins (1): NP_008883* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008952	Tetraspanin_EC2_sf	Homologous_superfamily
IPR018499	Tetraspanin/Peripherin	Family

Pfam: PF00335

UniProt features (12 total): topological domain 5, transmembrane region 4, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75841-F1	86.32	0.46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (2): response to bacterium (GO:0009617), epithelial cell differentiation (GO:0030855)

GO Molecular Function (2): structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (4): membrane (GO:0016020), extracellular exosome (GO:0070062), apical plasma membrane urothelial plaque (GO:0120001), apical plasma membrane (GO:0016324)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane region	2
response to other organism	1
cell differentiation	1
epithelium development	1
molecular_function	1
binding	1
cellular anatomical structure	1
extracellular vesicle	1
plasma membrane	1
apical plasma membrane	1
apical part of cell	1

Protein interactions and networks

STRING

723 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UPK1B	UPK3A	O75631	999
UPK1B	UPK2	O00526	999
UPK1B	PMS2P11	Q13670	965
UPK1B	UPK1A	O00322	939
UPK1B	CD53	P19397	714
UPK1B	CD37	P11049	697
UPK1B	B4E171	B4E171	636
UPK1B	ANXA10	Q9UJ72	620
UPK1B	KRT20	P35900	531
UPK1B	GPM6A	P51674	530
UPK1B	PTGFRN	Q9P2B2	481
UPK1B	PSEN2	P49810	464
UPK1B	SCARB2	Q14108	456
UPK1B	PTPRH	Q9HD43	451
UPK1B	GSAP	A4D1B5	450

IntAct

153 interactions, top by confidence:

A	B	Type	Score
UPK1B	NEMP1	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	STX1A	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	MFF	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	KASH5	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	CD69	psi-mi:“MI:0915”(physical association)	0.560
	UPK1B	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	TMEM91	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	KLRC1	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	SYT9	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	GJA8	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	SLC10A2	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
GPR37L1	UPK1B	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	TMEM139	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	PLPP4	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	CERS4	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	SIT1	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	TMUB2	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	GPX8	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	VSIG1	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	TMEM54	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
TMEM262	UPK1B	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	RHCG	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (63): UPK1B (Two-hybrid), BCL2L13 (Two-hybrid), CCDC155 (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), UPK1B (Two-hybrid), GJA8 (Two-hybrid)

ESM2 similar proteins: A0A8M2B5N2, A0A8V0ZLT4, A1L157, O00322, O60637, O75841, P11049, P19075, P21926, P30409, P30413, P30932, P31053, P38572, P38573, P40239, P40240, P40241, Q0D289, Q2KHY8, Q2MJQ7, Q3SZR9, Q4R4Z3, Q4R7W6, Q566D0, Q568Y5, Q58CY8, Q5RDV7, Q5RE11, Q5RH71, Q61470, Q6AYR9, Q6GQF5, Q6P0C6, Q6ZUX7, Q80WR1, Q8WMQ3, Q91Y55, Q925N4, Q96FX8

Diamond homologs: O00322, O75841, P30413, P38572, P38573, Q566D0, Q9D132, Q9Z2C6, O35566, P48509, P61170, P61171, Q9QZA6, Q9XVM9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

41 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1316 predictions. Top by Δscore:

Variant	Effect	Δscore
3:119173631:G:GT	donor_gain	1.0000
3:119173634:GCGCT:G	donor_gain	1.0000
3:119173636:GCT:G	donor_gain	1.0000
3:119173639:G:GG	donor_gain	1.0000
3:119187773:A:AG	acceptor_gain	1.0000
3:119187774:G:GG	acceptor_gain	1.0000
3:119187774:GT:G	acceptor_gain	1.0000
3:119187972:GGCG:G	donor_gain	1.0000
3:119187973:GCGG:G	donor_gain	1.0000
3:119187976:G:GG	donor_gain	1.0000
3:119187976:GTA:G	donor_loss	1.0000
3:119187977:TAAGA:T	donor_loss	1.0000
3:119190243:A:AG	acceptor_gain	1.0000
3:119190244:G:GG	acceptor_gain	1.0000
3:119190244:GT:G	acceptor_gain	1.0000
3:119190320:G:GG	donor_gain	1.0000
3:119190980:A:AG	acceptor_gain	1.0000
3:119190981:G:GG	acceptor_gain	1.0000
3:119190981:GTTC:G	acceptor_gain	1.0000
3:119190981:GTTCA:G	acceptor_gain	1.0000
3:119191101:CCAGG:C	donor_loss	1.0000
3:119191102:CAGGT:C	donor_loss	1.0000
3:119191103:AGGT:A	donor_loss	1.0000
3:119191104:GGTA:G	donor_loss	1.0000
3:119191105:GTA:G	donor_loss	1.0000
3:119191106:T:G	donor_loss	1.0000
3:119173637:CT:C	donor_gain	0.9900
3:119173637:CTGT:C	donor_loss	0.9900
3:119173638:TGTG:T	donor_loss	0.9900
3:119173639:G:GC	donor_loss	0.9900

AlphaMissense

1739 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:119194254:G:C	W168C	1.000
3:119194254:G:T	W168C	1.000
3:119191084:T:A	W150R	0.999
3:119191084:T:C	W150R	0.999
3:119191086:G:C	W150C	0.999
3:119191086:G:T	W150C	0.999
3:119194228:T:A	C160S	0.999
3:119194229:G:A	C160Y	0.999
3:119194229:G:C	C160S	0.999
3:119194252:T:A	W168R	0.999
3:119194252:T:C	W168R	0.999
3:119194318:T:A	C190S	0.999
3:119194318:T:C	C190R	0.999
3:119194319:G:C	C190S	0.999
3:119194321:T:A	C191S	0.999
3:119194322:G:C	C191S	0.999
3:119194363:T:A	C205S	0.999
3:119194364:G:C	C205S	0.999
3:119187901:G:C	G66R	0.998
3:119194225:T:A	C159S	0.998
3:119194225:T:C	C159R	0.998
3:119194226:G:C	C159S	0.998
3:119194227:C:G	C159W	0.998
3:119194228:T:C	C160R	0.998
3:119194229:G:T	C160F	0.998
3:119194230:T:G	C160W	0.998
3:119194253:G:C	W168S	0.998
3:119194306:T:A	W186R	0.998
3:119194306:T:C	W186R	0.998
3:119194319:G:A	C190Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000106750 (3:119180406 C>A), RS1000195042 (3:119191666 C>T), RS1000215704 (3:119192242 A>G), RS1000285347 (3:119188275 C>T), RS1000347193 (3:119204892 G>A), RS1000421020 (3:119204633 T>C,G), RS1000509139 (3:119177814 A>G), RS1000538964 (3:119178116 G>A), RS1000718166 (3:119173951 C>T), RS1000725476 (3:119192043 C>G), RS1000746294 (3:119173700 T>A), RS1000885119 (3:119195645 A>C), RS1001104633 (3:119203417 T>C), RS1001260634 (3:119205020 A>G), RS1001273040 (3:119193806 A>T)

Disease associations

OMIM: gene MIM:602380 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007643_2	Gemcitabine-induced early high-grade neutropenia in pancreatic cancer	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression, decreases expression	3
Benzo(a)pyrene	decreases methylation, increases methylation, affects methylation	2
Tobacco Smoke Pollution	affects expression, increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Allergens	increases expression	1
Atrazine	increases expression	1
Cadmium	increases expression	1
Cisplatin	affects response to substance	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	increases expression	1
Mustard Gas	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.