HLF

Summary

HLF (HLF transcription factor, PAR bZIP family member, HGNC:4977) is a protein-coding gene on chromosome 17q22, encoding Hepatic leukemia factor (Q16534).

This gene encodes a member of the proline and acidic-rich (PAR) protein family, a subset of the bZIP transcription factors. The encoded protein forms homodimers or heterodimers with other PAR family members and binds sequence-specific promoter elements to activate transcription. Chromosomal translocations fusing portions of this gene with the E2A gene cause a subset of childhood B-lineage acute lymphoid leukemias. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Source: NCBI Gene 3131 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 28 total
• Transcription factor: yes — 18 downstream targets (CollecTRI)
• MANE Select transcript: NM_002126

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4977
Approved symbol	HLF
Name	HLF transcription factor, PAR bZIP family member
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	MGC33822
Ensembl gene	ENSG00000108924
Ensembl biotype	protein_coding
OMIM	142385
Entrez	3131

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000226067, ENST00000430986, ENST00000570962, ENST00000572002, ENST00000572234, ENST00000573020, ENST00000573422, ENST00000573945, ENST00000575307, ENST00000575345, ENST00000575868

RefSeq mRNA: 2 — MANE Select: NM_002126 NM_001330375, NM_002126

CCDS: CCDS11585, CCDS82164

Canonical transcript exons

ENST00000226067 — 4 exons

Exon	Start	End
ENSE00001013153	55320664	55325187
ENSE00002269744	55264960	55265599
ENSE00003633330	55267751	55268086
ENSE00003679396	55315227	55315447

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 95.15.

FANTOM5 (CAGE): breadth broad, TPM avg 8.2388 / max 395.4212, expressed in 471 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161766	6.4077	459
161773	0.7363	134
161774	0.5588	129
161772	0.2117	86
161767	0.1483	75
161768	0.0636	39
161778	0.0415	4
161769	0.0316	13
161770	0.0256	6
161771	0.0137	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.15	gold quality
orbitofrontal cortex	UBERON:0004167	95.08	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.01	gold quality
superior frontal gyrus	UBERON:0002661	94.95	gold quality
prefrontal cortex	UBERON:0000451	94.51	gold quality
middle temporal gyrus	UBERON:0002771	94.41	gold quality
postcentral gyrus	UBERON:0002581	94.13	gold quality
parietal lobe	UBERON:0001872	94.07	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.96	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.93	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.82	gold quality
lower esophagus	UBERON:0013473	93.76	gold quality
tongue squamous epithelium	UBERON:0006919	93.38	gold quality
frontal cortex	UBERON:0001870	93.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.58	gold quality
occipital lobe	UBERON:0002021	92.53	gold quality
left ovary	UBERON:0002119	92.17	gold quality
primary visual cortex	UBERON:0002436	92.13	gold quality
liver	UBERON:0002107	91.83	gold quality
neocortex	UBERON:0001950	91.66	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.23	gold quality
right lobe of liver	UBERON:0001114	90.72	gold quality
parotid gland	UBERON:0001831	90.71	gold quality
entorhinal cortex	UBERON:0002728	90.51	gold quality
cerebral cortex	UBERON:0000956	90.44	gold quality
right frontal lobe	UBERON:0002810	90.15	gold quality
cingulate cortex	UBERON:0003027	90.04	gold quality
Brodmann (1909) area 10	UBERON:0013541	90.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	26.26
E-ANND-3	yes	14.83
E-MTAB-7316	yes	13.99

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

18 targets.

Target	Regulation
ABCB1	Unknown
BIRC5	Unknown
CD33
CYP7A1
DBP	Activation
EPO
F8	Activation
FGF2
HLA-E
JTB
LMO2	Activation
PER2
RUNX1	Repression
TLE2	Activation
TLE6	Activation
TNF
TSHB
VEGFA	Activation

JASPAR motifs

Motif	Name	Family
MA0043.1	HLF	CEBP-related
MA0043.2	HLF	CEBP-related
MA0043.3	HLF	CEBP-related
MA0043.4	HLF	CEBP-related

JASPAR matrix evidence (PMIDs): PMID:8065331

Upstream regulators (CollecTRI, top): BMAL1

miRNA regulators (miRDB)

245 targeting HLF, 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-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6867-5P	100.00	82.21	3464
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-4692	100.00	67.32	2066
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559

Literature-anchored findings (GeneRIF, showing 26)

• Evidence pertaining to leukemogenesis by the well-characterized oncogenic fusion protein E2A-HLF is reviewed and its mechanistic implications are considered. (PMID:12700034)
• E2A-HLF induces annexin II by substituting for cytokines that activate downstream pathways of Ras (PMID:15070701)
• The E2A-HLF-mediated over-expression of ABCB1 may play a role in the clinical phenotype of ALLs with a t(17;19), suggesting pharmacologic modulation of ABCB1 activity as a rational therapeutic strategy for this chemotherapy resistant subtype of ALL. (PMID:16206189)
• The patients with immunophenotype of Pre-B-acute lymphoblastic leukemia were found to carry: E2A/PBX1 and E2A/HLF. (PMID:16215946)
• In childhood acute lymphoblastic leukemia and hypercalcemia, translocation was observed in E2A-HLF fusion protein. (PMID:17183364)
• Activation of the thyroid hormone receptor beta/retinoid X receptor alpha heterodimer by T(3) stimulated expression of the hepatic leukemia factor, which increases HIF-1alpha gene expression. (PMID:18239067)
• E2A-HLF promotes cell survival of t(17;19)- acute lymphoblastic leukemia cells by aberrantly up-regulating LMO2 expression (PMID:20519628)
• both Lmo2 and Bcl-2 are required for the action of E2A-HLF in leukemogenesis (PMID:21072044)
• ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. (PMID:23415677)
• Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids. (PMID:26214592)
• HLF-mediated miR-132 directly suppresses TTK expression, thus exerting inhibitory effects on cancer cell proliferation, metastasis and radioresistance. (PMID:27522003)
• Poly (ADP-ribose) polymerase inhibitors selectively induce cytotoxicity in TCF3-HLF-positive leukemic cells. (PMID:27894958)
• our data establish HLF as a crucial transcription factor in triple-mutated AML, which modulates cell cycle dynamics and maintains the CD34+GPR56+ LSC-enriched compartment in this high-risk genetic subgroup. (PMID:31076446)
• Our findings uncovered HLF as a novel oncofetal protein and revealed the crucial role of the HLF/c-Jun axis in HCC development and sorafenib response, rendering HLF as an optimal target for the prevention and intervention of HCC (PMID:31118247)
• Downregulation of the circadian rhythm regulator HLF promotes multiple-organ distant metastases in non-small cell lung cancer through PPAR/NF-kappab signaling. (PMID:32289442)
• Genetic Analysis Identifies the Role of HLF in Renal Cell Carcinoma. (PMID:33099483)
• Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma. (PMID:33979320)
• HLF expression defines the human hematopoietic stem cell state. (PMID:34499717)
• FLT3-ITD allelic ratio and HLF expression predict FLT3 inhibitor efficacy in adult AML. (PMID:34876631)
• Integrative Molecular Analyses of an Individual Transcription Factor-Based Genomic Model for Lung Cancer Prognosis. (PMID:34925645)
• HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk. (PMID:34991659)
• CircCHD2/miR-200b-3p/HLF Axis Promotes Liver Cirrhosis. (PMID:36374958)
• m6A RNA methylation-mediated upregulation of HLF promotes intrahepatic cholangiocarcinoma progression by regulating the FZD4/beta-catenin signaling pathway. (PMID:36958694)
• HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway. (PMID:37709768)
• Tensin 1 regulated by hepatic leukemia factor represses the progression of prostate cancer. (PMID:37712764)
• The authors characterize variants of rat HLF, including use of two alternative promoters and a non-AUG translation initiation site that has not been confirmed in human. (PMID:7556072)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	hlfb	ENSDARG00000061011
danio_rerio	hlfa	ENSDARG00000074752
mus_musculus	Hlf	ENSMUSG00000003949
rattus_norvegicus	Hlf	ENSRNOG00000074026
drosophila_melanogaster	Pdp1	FBGN0016694
drosophila_melanogaster	CG7786	FBGN0034096
caenorhabditis_elegans		WBGENE00011130
caenorhabditis_elegans		WBGENE00017535

Paralogs (2): DBP (ENSG00000105516), TEF (ENSG00000167074)

Protein

Protein identifiers

Hepatic leukemia factor — Q16534 (reviewed: Q16534)

All UniProt accessions (3): Q16534, I3L386, I3L4R4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Binds DNA specifically as homodimer or heterodimer with other PAR factors.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in liver; lower levels in lung and kidney.

Disease relevance. A chromosomal aberration involving HLF is a cause of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(17;19)(q22;p13.3) with TCF3.

Induction. Accumulates according to a robust circadian rhythm.

Similarity. Belongs to the bZIP family. PAR subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16534-1	1	yes
Q16534-2	2

RefSeq proteins (2): NP_001317304, NP_002117* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR040223	PAR_bZIP	Family
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF07716

UniProt features (9 total): region of interest 4, chain 1, domain 1, compositionally biased region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16534-F1	72.55	0.41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, AAGCAAT_MIR137, GOBP_MUSCLE_TISSUE_DEVELOPMENT, JAEGER_METASTASIS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TATTATA_MIR374, GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_DN, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_4NM_UP, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_5, BOYAULT_LIVER_CANCER_SUBCLASS_G12_DN, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, DELYS_THYROID_CANCER_DN, AAAGACA_MIR511, CHIANG_LIVER_CANCER_SUBCLASS_INTERFERON_DN

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), skeletal muscle cell differentiation (GO:0035914), positive regulation of transcription by RNA polymerase II (GO:0045944), rhythmic process (GO:0048511), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
DNA binding	2
cellular anatomical structure	2
skeletal muscle tissue development	1
cell differentiation	1
positive regulation of DNA-templated transcription	1
biological_process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HLF	TLE6	Q9H808	788
HLF	SRPX2	O60687	760
HLF	TLE2	Q04725	755
HLF	TCF3	P15883	747
HLF	A0A087WTN9	A0A087WTN9	712
HLF	TFPT	P0C1Z6	698
HLF	BMAL1	O00327	655
HLF	PRCC	Q92733	649
HLF	CRY1	Q16526	622
HLF	CRY2	Q49AN0	576
HLF	NR1D1	P20393	547
HLF	NFIL3	Q16649	545
HLF	TFEB	P19484	535
HLF	TFE3	P19532	529
HLF	RUNX1	Q01196	522

IntAct

45 interactions, top by confidence:

A	B	Type	Score
HLF	DDIT3	psi-mi:“MI:0407”(direct interaction)	0.620
HLF	BATF	psi-mi:“MI:0407”(direct interaction)	0.620
HLF	BATF3	psi-mi:“MI:0407”(direct interaction)	0.620
DDIT3	HLF	psi-mi:“MI:0407”(direct interaction)	0.620
HLF	DBP	psi-mi:“MI:0407”(direct interaction)	0.590
DBP	HLF	psi-mi:“MI:0407”(direct interaction)	0.590
HLF	DBP	psi-mi:“MI:0915”(physical association)	0.590
HLF	HLF	psi-mi:“MI:0407”(direct interaction)	0.440
NFIL3	HLF	psi-mi:“MI:0407”(direct interaction)	0.440
HLF	JUN	psi-mi:“MI:0407”(direct interaction)	0.440
HLF	BATF2	psi-mi:“MI:0407”(direct interaction)	0.440
HLF	TLK1	psi-mi:“MI:0915”(physical association)	0.400
	HLF	psi-mi:“MI:0915”(physical association)	0.400
HLF	HNF4G	psi-mi:“MI:0915”(physical association)	0.370
HLF	MYB	psi-mi:“MI:0915”(physical association)	0.370
CBX8	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
HLF	gatA	psi-mi:“MI:0915”(physical association)	0.000
pheS	HLF	psi-mi:“MI:0915”(physical association)	0.000
recJ	HLF	psi-mi:“MI:0915”(physical association)	0.000
sbcB	HLF	psi-mi:“MI:0915”(physical association)	0.000
HLF		psi-mi:“MI:0915”(physical association)	0.000
HLF	rsmI	psi-mi:“MI:0915”(physical association)	0.000
rpoB	HLF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): TLK1 (Affinity Capture-MS), CREBBP (Two-hybrid), CREBBP (Reconstituted Complex), HLF (Two-hybrid), TET2 (Affinity Capture-Western), TLK1 (Affinity Capture-MS), HLF (Cross-Linking-MS (XL-MS)), HNF4G (Two-hybrid), MYB (Two-hybrid), HLF (Two-hybrid)

ESM2 similar proteins: A0A179H0U5, A0A1R3RGK4, A0A1U8QIH0, A0A348HAZ0, A2R6G8, A2T713, A2T7L8, A2X0Q0, A4IFU7, B3FWS0, B8ANX9, B8N0E6, G0LEU0, G5ECU7, G5EF15, I1S2J8, I1S491, O14948, O42261, O88368, P15315, P20945, P24813, P26798, P80073, Q01663, Q09771, Q10LZ1, Q16534, Q22835, Q23359, Q2U9L6, Q2UJJ4, Q4W9W8, Q4WVQ7, Q5RFT9, Q5XFQ6, Q63302, Q6NVN3, Q6Q877

Diamond homologs: A0A5F9ZHS7, O08750, P16443, P41224, P97516, Q08D88, Q10586, Q10587, Q16534, Q16649, Q32PF6, Q5FW38, Q60925, Q64709, Q66J36, Q68EL6, Q6IMZ0, Q8BW74, Q90Z72, Q92172, Q94126, Q9JLC6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HLF	down-regulates	Apoptosis
HLF	down-regulates	Cell_death

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	5	292.6×	5e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:55267843:T:A	W70R	1.000
17:55267843:T:C	W70R	1.000
17:55267845:G:C	W70C	1.000
17:55267845:G:T	W70C	1.000
17:55267883:T:C	L83S	1.000
17:55267898:T:A	L88Q	1.000
17:55267898:T:C	L88P	1.000
17:55267906:T:C	F91L	1.000
17:55267907:T:C	F91S	1.000
17:55267907:T:G	F91C	1.000
17:55267908:T:A	F91L	1.000
17:55267908:T:G	F91L	1.000
17:55267910:T:C	L92S	1.000
17:55315320:T:C	L182P	1.000
17:55315352:T:C	F193L	1.000
17:55315353:T:C	F193S	1.000
17:55315353:T:G	F193C	1.000
17:55315354:T:A	F193L	1.000
17:55315354:T:G	F193L	1.000
17:55315358:C:T	P195S	1.000
17:55315359:C:A	P195H	1.000
17:55315359:C:G	P195R	1.000
17:55315373:T:C	F200L	1.000
17:55315374:T:C	F200S	1.000
17:55315374:T:G	F200C	1.000
17:55315375:C:A	F200L	1.000
17:55315375:C:G	F200L	1.000
17:55315389:T:C	L205P	1.000
17:55315394:C:T	P207S	1.000
17:55315395:C:A	P207Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000024666 (17:55274669 C>A), RS1000051616 (17:55282193 G>A), RS1000089084 (17:55296349 A>G), RS1000135236 (17:55322745 G>A,T), RS1000276980 (17:55289475 C>T), RS1000286790 (17:55283067 G>A), RS1000302267 (17:55287793 C>T), RS1000334527 (17:55325642 G>A), RS1000395986 (17:55293746 T>C), RS1000402219 (17:55323020 A>G), RS1000402587 (17:55283419 G>A), RS1000431752 (17:55302168 G>C), RS1000560312 (17:55291486 C>T), RS1000612769 (17:55291152 A>G), RS1000711109 (17:55265331 A>C,G)

Disease associations

OMIM: gene MIM:142385 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001791_37	Urate levels	5.000000e-17
GCST002263_6	Acute urticaria and angioedema (non-steroidal anti-inflammatory drug-induced)	4.000000e-06
GCST002828_3	Urate levels in obese individuals	6.000000e-06
GCST002934_5	Zinc levels	9.000000e-07
GCST003542_23	Night sleep phenotypes	4.000000e-06
GCST007733_52	Serum uric acid levels	3.000000e-12
GCST008103_45	Bipolar disorder	2.000000e-07
GCST008103_54	Bipolar disorder	4.000000e-07
GCST008151_91	Waist circumference	7.000000e-07
GCST008152_140	Weight	6.000000e-06
GCST008160_91	Waist circumference	7.000000e-07
GCST008971_134	Urate levels	1.000000e-21
GCST008972_135	Urate levels	9.000000e-23
GCST009391_1551	Metabolite levels	4.000000e-07
GCST010242_270	HDL cholesterol levels	2.000000e-09
GCST010637_24	Urate levels	2.000000e-12
GCST011102_20	Bipolar disorder	6.000000e-10
GCST90002383_73	Hematocrit	3.000000e-09
GCST90002384_419	Hemoglobin	7.000000e-11
GCST90002401_552	Platelet distribution width	3.000000e-09
GCST90002403_364	Red blood cell count	2.000000e-09

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0005533	response to non-steroidal anti-inflammatory
EFO:0004761	uric acid measurement
EFO:0004338	body weight
EFO:0009776	ornithine measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007984	platelet component distribution width
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, decreases methylation, affects expression	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Valproic Acid	affects expression, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
Estradiol	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
geraniol	decreases expression	1
kojic acid	decreases expression	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Arbutin	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1
Demecolcine	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1242	HAL-01	Cancer cell line	Female
CVCL_A082	YCUB-2	Cancer cell line	Male
CVCL_A296	UoC-B1	Cancer cell line	Female
CVCL_A2BM	Endo-kun	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer