UPK3B

Summary

UPK3B (uroplakin 3B, HGNC:21444) is a protein-coding gene on chromosome 7q11.23, encoding Uroplakin-3b (Q9BT76). Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells.

UPK3B is a minor component of the apical plaques of mammalian urothelium that binds and dimerizes with uroplakin-1b (UPK1B; MIM 602380), one of the major conserved urothelium membrane proteins. The other major conserved integral membrane proteins of urothelial plaques are UPK1A (MIM 611557), UPK2 (MIM 611558), and UPK3A (MIM 611559) (Deng et al., 2002 [PubMed 12446744]).

Source: NCBI Gene 105375355 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 93 total
• MANE Select transcript: NM_001347684

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21444
Approved symbol	UPK3B
Name	uroplakin 3B
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	MGC10902, p35, UPIIIb, FLJ32198
Ensembl gene	ENSG00000243566
Ensembl biotype	protein_coding
OMIM	611887
Entrez	105375355

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 retained_intron

ENST00000257632, ENST00000334348, ENST00000394849, ENST00000469114, ENST00000490360, ENST00000911147

RefSeq mRNA: 1 — MANE Select: NM_001347684 NM_001347684

CCDS: CCDS87512

Canonical transcript exons

ENST00000334348 — 6 exons

Exon	Start	End
ENSE00001127602	76510903	76511052
ENSE00001519794	76510552	76510737
ENSE00003587310	76513947	76514076
ENSE00003620406	76511657	76511882
ENSE00003634115	76513084	76513163
ENSE00003635875	76515045	76516522

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 99.40.

FANTOM5 (CAGE): breadth broad, TPM avg 7.7535 / max 926.8590, expressed in 445 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79180	4.6989	387
79182	1.3252	206
79181	0.6256	188
79177	0.6185	208
79179	0.3188	139
79176	0.1013	47
79178	0.0651	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.40	gold quality
right lung	UBERON:0002167	95.06	gold quality
upper lobe of left lung	UBERON:0008952	92.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.74	gold quality
esophagus mucosa	UBERON:0002469	89.39	gold quality
omental fat pad	UBERON:0010414	87.96	gold quality
lung	UBERON:0002048	87.93	gold quality
urinary bladder	UBERON:0001255	79.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	77.57	gold quality
right uterine tube	UBERON:0001302	76.53	gold quality
esophagus	UBERON:0001043	75.89	gold quality
skin of leg	UBERON:0001511	74.91	gold quality
adipose tissue	UBERON:0001013	74.88	gold quality
zone of skin	UBERON:0000014	74.59	gold quality
vagina	UBERON:0000996	74.36	gold quality
minor salivary gland	UBERON:0001830	74.36	gold quality
skin of abdomen	UBERON:0001416	74.24	gold quality
sural nerve	UBERON:0015488	73.98	gold quality
blood	UBERON:0000178	73.52	gold quality
left uterine tube	UBERON:0001303	73.24	gold quality
saliva-secreting gland	UBERON:0001044	73.14	gold quality
fallopian tube	UBERON:0003889	71.25	gold quality
right coronary artery	UBERON:0001625	69.56	gold quality
uterine cervix	UBERON:0000002	69.40	gold quality
mucosa of stomach	UBERON:0001199	69.31	gold quality
mucosa of transverse colon	UBERON:0004991	69.15	gold quality
ectocervix	UBERON:0012249	68.94	gold quality
tonsil	UBERON:0002372	68.45	gold quality
left ovary	UBERON:0002119	67.84	gold quality
spleen	UBERON:0002106	67.80	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• LRRN4 was only detected in primary mesothelial cells, but MSLN and UPK3B were also detected in other cell types. (PMID:21984916)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	upk3b	ENSDARG00000092872
mus_musculus	Upk3b	ENSMUSG00000042985
rattus_norvegicus	Upk3b	ENSRNOG00000023686

Paralogs (3): UPK3A (ENSG00000100373), UPK3BL1 (ENSG00000267368), UPK3BL2 (ENSG00000284981)

Protein

Protein identifiers

Uroplakin-3b — Q9BT76 (reviewed: Q9BT76)

Alternative names: Uroplakin IIIb, p35

All UniProt accessions (1): Q9BT76

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 AUM-cytoskeleton interaction in terminally differentiated urothelial cells. It also contributes to the formation of urothelial glycocalyx which may play an important role in preventing bacterial adherence.

Subunit / interactions. Heterodimer with uroplakin-1B (UPK1B).

Subcellular location. Cell membrane.

Similarity. Belongs to the uroplakin-3 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BT76-1	1	yes
Q9BT76-2	2
Q9BT76-3	3

RefSeq proteins (1): NP_001334613* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024831	Uroplakin-3	Family

UniProt features (11 total): sequence variant 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT76-F1	52.61	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 133

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_TRANS, chr7q11, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_9, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, MIKKELSEN_ES_ICP_WITH_H3K4ME3, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, ERBB2_UP.V1_UP, GCNP_SHH_UP_EARLY.V1_DN, MEK_UP.V1_UP, PRC2_SUZ12_UP.V1_UP, KRAS.600.LUNG.BREAST_UP.V1_DN, KRAS.LUNG_UP.V1_DN, KRAS.LUNG.BREAST_UP.V1_DN, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_DN

GO Biological Process (1): negative regulation of gene expression (GO:0010629)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

9 interactions, top by confidence:

A	B	Type	Score
UPK3B	AP1G2	psi-mi:“MI:0914”(association)	0.560
AP1G2	UPK3B	psi-mi:“MI:0915”(physical association)	0.560
UPK3B	rep	psi-mi:“MI:0915”(physical association)	0.550
UPK3B		psi-mi:“MI:0915”(physical association)	0.370
CFTR	UPK3B	psi-mi:“MI:0915”(physical association)	0.370
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
UPK3B	HSPA5	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): HSPA5 (Affinity Capture-MS), MYO18A (Affinity Capture-MS), MYO18A (Affinity Capture-MS), UPK3B (Affinity Capture-MS), UPK3B (Affinity Capture-MS), MYO18A (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), DDX19B (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), SLC25A15 (Affinity Capture-MS), TRMT2A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), FAM136A (Affinity Capture-MS), AP1G2 (Affinity Capture-MS), UPK3B (Two-hybrid)

ESM2 similar proteins: C9JLR9, D3YZZ2, E1BDF2, E7ERA6, O00110, P0DH78, P29590, P51172, P70225, Q01113, Q02833, Q0VCS0, Q13477, Q13505, Q14626, Q32KV8, Q3UIW8, Q3UV31, Q4R7H0, Q4VA45, Q5R866, Q5RF19, Q5U4P2, Q5VTJ3, Q64385, Q6BAA4, Q6ISU1, Q6ZVT0, Q70EL4, Q7L591, Q86UR1, Q8IYG6, Q8N1F8, Q8N554, Q8NFT6, Q969Z4, Q96G42, Q96HA4, Q96IQ9, Q99640

Diamond homologs: A6QQ85, B0FP48, E5RIL1, Q13670, Q80YF6, Q864V4, Q9BT76, Q9D701, A0B977, A1AJ76, A4D2B8, A4TRP1, A4W5R1, A5F3L5, A5UFN4, A6SV55, A7FMY1, A7HNR3, A7ZV39, A8A7R4, A8AMN1, A8FRD3, A9BJB9, A9M0G1, A9MFP2, A9N4Y4, A9QYN3, B0K1A3, B0K9L6, B0TB10, B1IT36, B1JMP1, B1LQJ0, B1XDS1, B2II71, B2K202, B2TY45, B2VCU8, B3PDC3, B4T2R5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	16
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

741 predictions. Top by Δscore:

Variant	Effect	Δscore
7:76510901:A:AG	acceptor_gain	1.0000
7:76510902:G:GG	acceptor_gain	1.0000
7:76511050:ATG:A	donor_gain	1.0000
7:76511053:G:GG	donor_gain	1.0000
7:76511053:GTAC:G	donor_loss	1.0000
7:76511054:T:A	donor_loss	1.0000
7:76514077:G:GG	donor_gain	1.0000
7:76510894:T:TA	acceptor_gain	0.9900
7:76510902:GA:G	acceptor_gain	0.9900
7:76510902:GAGCT:G	acceptor_gain	0.9900
7:76511051:TG:T	donor_gain	0.9900
7:76511052:GG:G	donor_gain	0.9900
7:76511655:A:AG	acceptor_gain	0.9900
7:76511656:G:GC	acceptor_gain	0.9900
7:76511656:GC:G	acceptor_gain	0.9900
7:76511881:CGGTG:C	donor_loss	0.9900
7:76511884:T:G	donor_loss	0.9900
7:76511889:G:GA	donor_gain	0.9900
7:76514073:GCTT:G	donor_gain	0.9900
7:76515038:C:A	acceptor_gain	0.9900
7:76510736:GG:G	donor_gain	0.9800
7:76510737:GG:G	donor_gain	0.9800
7:76510895:G:A	acceptor_gain	0.9800
7:76511652:T:A	acceptor_gain	0.9800
7:76511652:TGCA:T	acceptor_loss	0.9800
7:76511652:TGCAG:T	acceptor_gain	0.9800
7:76511655:A:AC	acceptor_loss	0.9800
7:76511656:GCC:G	acceptor_gain	0.9800
7:76511656:GCCT:G	acceptor_gain	0.9800
7:76511656:GCCTC:G	acceptor_gain	0.9800

AlphaMissense

1776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:76510968:T:C	F106L	0.989
7:76510970:C:A	F106L	0.989
7:76510970:C:G	F106L	0.989
7:76511668:T:C	F138L	0.988
7:76511670:C:A	F138L	0.988
7:76511670:C:G	F138L	0.988
7:76510969:T:C	F106S	0.979
7:76511669:T:G	F138C	0.979
7:76510969:T:G	F106C	0.974
7:76511030:G:C	W126C	0.969
7:76511030:G:T	W126C	0.969
7:76511669:T:C	F138S	0.966
7:76511028:T:A	W126R	0.963
7:76511028:T:C	W126R	0.963
7:76510927:T:C	I92T	0.946
7:76511032:T:C	L127P	0.940
7:76511043:T:C	F131L	0.939
7:76511045:C:A	F131L	0.939
7:76511045:C:G	F131L	0.939
7:76511853:C:A	N199K	0.935
7:76511853:C:G	N199K	0.935
7:76511736:G:A	M160I	0.933
7:76511736:G:C	M160I	0.933
7:76511736:G:T	M160I	0.933
7:76511849:G:A	C198Y	0.931
7:76511032:T:A	L127H	0.928
7:76510947:G:T	G99W	0.926
7:76510963:C:T	T104I	0.924
7:76510947:G:A	G99R	0.923
7:76510947:G:C	G99R	0.923

dbSNP variants (sampled 300 via entrez): RS1000519632 (7:76513798 CG>C,CGG), RS1000529514 (7:76513627 A>T), RS1001518402 (7:76514829 C>T), RS1001877179 (7:76508892 A>G), RS1002477699 (7:76510103 T>C), RS1002837605 (7:76510341 G>A,C), RS1003041929 (7:76515742 T>C), RS1003425617 (7:76511820 TG>T), RS1006440540 (7:76515339 G>A,T), RS1008327118 (7:76512883 G>A), RS1008843148 (7:76512503 G>A), RS1009383811 (7:76513663 C>T), RS1010222116 (7:76509471 C>T), RS1010288152 (7:76514861 A>T), RS1010383070 (7:76514494 T>C)

Disease associations

OMIM: gene MIM:611887 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002333_8	Bone properties (heel)	1.000000e-07
GCST004557_196	Body mass index	5.000000e-06
GCST004557_225	Body mass index	7.000000e-09
GCST004558_145	Body mass index (joint analysis main effects and physical activity interaction)	5.000000e-09
GCST004558_93	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-06
GCST004559_88	Body mass index in physically active individuals	5.000000e-06
GCST004560_41	Body mass index in physically inactive individuals	6.000000e-06
GCST010988_160	Adult body size	1.000000e-19
GCST010989_119	Body size at age 10	5.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005654	velocity of sound measurement
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression	3
Air Pollutants	affects expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
sotorasib	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
abrine	decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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