JTB

Summary

JTB (jumping translocation breakpoint, HGNC:6201) is a protein-coding gene on chromosome 1q21.3, encoding Protein JTB (O76095). Required for normal cytokinesis during mitosis. It is a selective cancer dependency (DepMap: 10.6% of cell lines).

Enables protein kinase binding activity. Involved in mitotic cytokinesis and positive regulation of protein kinase activity. Located in cytoplasm; microtubule cytoskeleton; and midbody.

Source: NCBI Gene 10899 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 38 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 10.6% of screened cell lines
• MANE Select transcript: NM_006694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6201
Approved symbol	JTB
Name	jumping translocation breakpoint
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	hJT, PAR
Ensembl gene	ENSG00000143543
Ensembl biotype	protein_coding
OMIM	604671
Entrez	10899

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000271843, ENST00000356648, ENST00000368589, ENST00000428469, ENST00000461365, ENST00000471173, ENST00000930486

RefSeq mRNA: 1 — MANE Select: NM_006694 NM_006694

CCDS: CCDS1057

Canonical transcript exons

ENST00000271843 — 5 exons

Exon	Start	End
ENSE00000960771	153975826	153975905
ENSE00001054082	153974269	153974835
ENSE00001361556	153977170	153977674
ENSE00003515468	153976693	153976775
ENSE00003547025	153976976	153977013

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 108.5340 / max 711.6513, expressed in 1828 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14759	92.1589	1827
14758	8.1035	1771
14760	7.7628	1767
14755	0.2736	109
14757	0.2353	101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.64	gold quality
ileal mucosa	UBERON:0000331	99.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.05	gold quality
colonic mucosa	UBERON:0000317	98.93	gold quality
tibia	UBERON:0000979	98.93	gold quality
pancreatic ductal cell	CL:0002079	98.90	gold quality
body of pancreas	UBERON:0001150	98.88	gold quality
upper leg skin	UBERON:0004262	98.85	gold quality
pituitary gland	UBERON:0000007	98.84	gold quality
adenohypophysis	UBERON:0002196	98.77	gold quality
choroid plexus epithelium	UBERON:0003911	98.64	gold quality
skin of hip	UBERON:0001554	98.59	gold quality
epithelial cell of pancreas	CL:0000083	98.58	silver quality
periodontal ligament	UBERON:0008266	98.55	gold quality
bronchial epithelial cell	CL:0002328	98.48	gold quality
palpebral conjunctiva	UBERON:0001812	98.47	gold quality
tibialis anterior	UBERON:0001385	98.46	gold quality
trabecular bone tissue	UBERON:0002483	98.46	gold quality
body of stomach	UBERON:0001161	98.39	gold quality
mucosa of transverse colon	UBERON:0004991	98.38	gold quality
epithelium of bronchus	UBERON:0002031	98.35	gold quality
saliva-secreting gland	UBERON:0001044	98.31	gold quality
granulocyte	CL:0000094	98.30	gold quality
bronchus	UBERON:0002185	98.29	gold quality
nasal cavity mucosa	UBERON:0001826	98.28	gold quality
nasal cavity epithelium	UBERON:0005384	98.27	gold quality
seminal vesicle	UBERON:0000998	98.25	gold quality
eye	UBERON:0000970	98.20	gold quality
visceral pleura	UBERON:0002401	98.20	gold quality
nephron tubule	UBERON:0001231	98.18	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6524	no	325.21
E-GEOD-124858	no	69.99
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DBP, HLF

miRNA regulators (miRDB)

40 targeting JTB, 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-3924	100.00	72.09	2394
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-562	97.66	65.63	698
HSA-MIR-3667-5P	97.16	64.87	591
HSA-MIR-1913	97.07	66.20	1417

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Among ten hepatocellular carcinoma cases with amplicon 1q21-q22, significant gene expression level of JTB, SHC1, CCT3 and COPA in the tumors than the paired adjacent non-malignant liver tissues. (PMID:12586295)
• Overexpression of JTB conferred resistance to apoptosis induced by ultraviolet radiation (PMID:19487072)
• Due to its involvement in cell cycle and its overexpression in several human cancers PAR could represent an attractive target for therapeutic intervention. (PMID:21225229)
• The JTB structure has a distant relationship to the midkine/pleiotrophin fold, particularly in the conservation of distinctive disulfide bridge patterns. (PMID:22079049)
• Downregulation of the PAR expression increases the Bax/Bcl-2 ratio and Bax expression, and thus induces the G2-M phase arrest and apoptosis of PC3 cells. (PMID:23297497)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	jtb	ENSDARG00000070150
mus_musculus	Jtb	ENSMUSG00000027937
rattus_norvegicus	Jtb	ENSRNOG00000016379
drosophila_melanogaster	JTBR	FBGN0025820
caenorhabditis_elegans		WBGENE00002180

Protein

Protein identifiers

Protein JTB — O76095 (reviewed: O76095)

Alternative names: Jumping translocation breakpoint protein, Prostate androgen-regulated protein

All UniProt accessions (1): O76095

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal cytokinesis during mitosis. Plays a role in the regulation of cell proliferation. May be a component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Increases AURKB activity. Inhibits apoptosis induced by TGFB1. Overexpression induces swelling of mitochondria and reduces mitochondrial membrane potential.

Subunit / interactions. Interacts with AURKA, AURKB, BIRC5 and INCENP. May be a component of the CPC at least composed of BIRC5/survivin, CDCA8/borealin, INCENP and AURKB/Aurora-B.

Subcellular location. Membrane. Mitochondrion. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle.

Tissue specificity. Ubiquitous. Expressed in all normal human tissues studied but overexpressed or underexpressed in many of their malignant counterparts.

Induction. Protein levels increase during the S phase of the cell cycle, are highest during G2 and mitosis, and decrease to low levels at G1. Levels are lowest at the transition from G1 to S phase.

Similarity. Belongs to the JTB family.

Isoforms (2)

UniProt ID	Names	Canonical?
O76095-1	1	yes
O76095-2	2

RefSeq proteins (1): NP_006685* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008657	JTB	Family

Pfam: PF05439

UniProt features (16 total): helix 3, turn 3, strand 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KJX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76095-F1	79.14	0.25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 176 (showing top): GOBP_MITOTIC_CYTOKINESIS, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_HDAC1, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, MORF_SKP1A, MORF_RAF1, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_CYTOKINESIS

GO Biological Process (7): mitotic cell cycle (GO:0000278), mitotic cytokinesis (GO:0000281), apoptotic mitochondrial changes (GO:0008637), regulation of cell population proliferation (GO:0042127), positive regulation of protein kinase activity (GO:0045860), apoptotic process (GO:0006915), cell division (GO:0051301)

GO Molecular Function (1): protein kinase binding (GO:0019901)

GO Cellular Component (8): cytoplasm (GO:0005737), mitochondrion (GO:0005739), centrosome (GO:0005813), spindle (GO:0005819), plasma membrane (GO:0005886), membrane (GO:0016020), midbody (GO:0030496), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membraneless organelle	2
cell cycle	1
mitotic nuclear division	1
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
apoptotic process	1
mitochondrion organization	1
cell population proliferation	1
regulation of cellular process	1
positive regulation of protein phosphorylation	1
protein kinase activity	1
positive regulation of kinase activity	1
regulation of protein kinase activity	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
kinase binding	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
JTB	PARD3	Q8TEW0	595
JTB	SCRIB	Q14160	573
JTB	CDC42	P21181	507
JTB	NR1I2	O75469	506
JTB	EPRS1	P07814	476
JTB	PALS1	Q8N3R9	447
JTB	TMEM47	Q9BQJ4	441
JTB	MSN	P26038	439
JTB	EZR	P15311	437
JTB	TP53	P04637	431
JTB	PARG	Q86W56	431
JTB	RDX	P35241	425
JTB	MARK2	Q7KZI7	377
JTB	PATJ	Q8NI35	372
JTB	NUMB	P49757	370

IntAct

10 interactions, top by confidence:

A	B	Type	Score
JTB	AURKA	psi-mi:“MI:0915”(physical association)	0.400
BIRC5	JTB	psi-mi:“MI:0915”(physical association)	0.400
JTB	UBE2S	psi-mi:“MI:0915”(physical association)	0.370
JTB	ELOC	psi-mi:“MI:0915”(physical association)	0.370
JTB	ZXDC	psi-mi:“MI:0915”(physical association)	0.370
GPR107	JTB	psi-mi:“MI:0914”(association)	0.350
TMED10	PGRMC1	psi-mi:“MI:0914”(association)	0.350
JTB	TMEM120B	psi-mi:“MI:0914”(association)	0.350
JTB	bipA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): JTB (Synthetic Lethality), JTB (Synthetic Lethality), LOX (Co-fractionation), JTB (Affinity Capture-RNA), JTB (Negative Genetic), XPO4 (Affinity Capture-MS), INTS12 (Affinity Capture-MS), MIPEP (Affinity Capture-MS), UTP20 (Affinity Capture-MS), TMEM120A (Affinity Capture-MS), NDC1 (Affinity Capture-MS), PIGQ (Affinity Capture-MS), SACM1L (Affinity Capture-MS), DCUN1D5 (Affinity Capture-MS), ATRIP (Affinity Capture-MS)

ESM2 similar proteins: A0A5F4BST2, A2A8U2, A5PLA0, A8MWV9, O76095, P15382, P15383, P23299, Q01114, Q08CB3, Q1RMB5, Q1RMT2, Q28705, Q2T9K0, Q3TS39, Q3URD2, Q502I1, Q5BJN9, Q5R8Q2, Q5SNT2, Q5T1S8, Q5T848, Q5XI52, Q60409, Q60943, Q810F0, Q86XR5, Q8BX43, Q8CJ26, Q8HYZ0, Q8JZL1, Q8K2Y3, Q8K5A9, Q8N112, Q8N4K4, Q8NFM7, Q91WM6, Q969Z4, Q96F46, Q96MH2

Diamond homologs: O76095, O77049, O88823, O88824

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	20
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625770	GRCh37/hg19 1q21.3(chr1:153701504-154218584)	Pathogenic

SpliceAI

599 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153975901:GTTTT:G	acceptor_gain	1.0000
1:153975902:TTTT:T	acceptor_gain	1.0000
1:153975903:TTT:T	acceptor_gain	1.0000
1:153975903:TTTC:T	acceptor_loss	1.0000
1:153975904:TT:T	acceptor_gain	1.0000
1:153975904:TTC:T	acceptor_loss	1.0000
1:153975905:TCTGC:T	acceptor_loss	1.0000
1:153975906:C:CA	acceptor_loss	1.0000
1:153975906:C:CC	acceptor_gain	1.0000
1:153975907:T:A	acceptor_loss	1.0000
1:153975910:C:CT	acceptor_gain	1.0000
1:153975910:C:T	acceptor_gain	1.0000
1:153975911:A:T	acceptor_gain	1.0000
1:153976691:A:AC	donor_gain	1.0000
1:153976692:C:CC	donor_gain	1.0000
1:153976692:CAG:C	donor_gain	1.0000
1:153974831:GGCAG:G	acceptor_gain	0.9900
1:153974832:GCAG:G	acceptor_gain	0.9900
1:153974833:CAG:C	acceptor_gain	0.9900
1:153974833:CAGC:C	acceptor_gain	0.9900
1:153974834:AG:A	acceptor_gain	0.9900
1:153974834:AGC:A	acceptor_loss	0.9900
1:153974835:GC:G	acceptor_loss	0.9900
1:153974836:C:CA	acceptor_loss	0.9900
1:153974836:C:CC	acceptor_gain	0.9900
1:153975821:CTCA:C	donor_loss	0.9900
1:153975822:TCACC:T	donor_loss	0.9900
1:153975823:CACC:C	donor_loss	0.9900
1:153975824:ACCT:A	donor_loss	0.9900
1:153975825:C:CG	donor_loss	0.9900

AlphaMissense

936 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153974701:C:G	R140P	0.984
1:153976735:A:C	F54L	0.981
1:153976735:A:T	F54L	0.981
1:153976737:A:G	F54L	0.981
1:153974802:A:C	F106L	0.978
1:153974802:A:T	F106L	0.978
1:153974804:A:G	F106L	0.978
1:153976750:C:A	W49C	0.972
1:153976750:C:G	W49C	0.972
1:153974803:A:C	F106C	0.971
1:153974694:T:A	Q142H	0.969
1:153974694:T:G	Q142H	0.969
1:153974793:G:C	F109L	0.969
1:153974793:G:T	F109L	0.969
1:153974795:A:G	F109L	0.969
1:153975889:C:G	C74S	0.967
1:153975890:A:T	C74S	0.967
1:153974734:C:G	R129P	0.965
1:153974833:C:G	C96S	0.964
1:153974834:A:T	C96S	0.964
1:153974687:A:G	S145P	0.963
1:153974741:G:T	R127S	0.963
1:153974740:C:G	R127P	0.962
1:153975890:A:G	C74R	0.962
1:153974706:C:A	K138N	0.960
1:153974706:C:G	K138N	0.960
1:153975856:C:G	C85S	0.960
1:153975857:A:T	C85S	0.960
1:153974790:T:A	E110D	0.958
1:153974790:T:G	E110D	0.958

dbSNP variants (sampled 300 via entrez): RS1001417388 (1:153975162 C>G), RS1002434171 (1:153974501 A>C,G), RS1002740228 (1:153975607 A>G), RS1002811548 (1:153974044 G>A), RS1003180750 (1:153975876 T>A), RS1003933237 (1:153976240 G>C), RS1003965762 (1:153976393 G>A,C), RS1005645058 (1:153978107 T>C,G), RS1005660229 (1:153974701 C>T), RS1005939528 (1:153979443 G>A,C), RS1006094545 (1:153979108 C>T), RS1006123968 (1:153979451 G>A), RS1006840430 (1:153978609 A>C), RS1008091717 (1:153976293 T>C), RS1008963064 (1:153974872 C>T)

Disease associations

OMIM: gene MIM:604671 | disease phenotypes: MIM:615074

GenCC curated gene-disease

Mondo (1): severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome (MONDO:0014034)

Orphanet (1): Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome (Orphanet:363686)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST010136_18	Fruit consumption	3.000000e-08
GCST010137_3	Cooked vegetable consumption	3.000000e-09
GCST010142_60	Fish- and plant-related diet	4.000000e-09
GCST010142_92	Fish- and plant-related diet	6.000000e-14
GCST010696_22	Cortical thickness (min-P)	4.000000e-10
GCST010697_50	Cortical surface area (min-P)	1.000000e-12
GCST010698_81	Subcortical volume (min-P)	1.000000e-23
GCST010699_7	Brain morphology (min-P)	1.000000e-10
GCST010700_11	Cortical thickness (MOSTest)	4.000000e-13
GCST010701_73	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_45	Subcortical volume (MOSTest)	4.000000e-10
GCST010703_276	Brain morphology (MOSTest)	2.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
chloropicrin	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	affects response to substance	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Metribolone	increases expression	1
Cyclosporine	increases expression	1
Sodium Selenite	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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