HDGF

Summary

HDGF (heparin binding growth factor, HGNC:4856) is a protein-coding gene on chromosome 1q23.1, encoding Hepatoma-derived growth factor (P51858). Acts as a transcriptional repressor.

This gene encodes a member of the hepatoma-derived growth factor family. The encoded protein has mitogenic and DNA-binding activity and may play a role in cellular proliferation and differentiation. High levels of expression of this gene enhance the growth of many tumors. This gene was thought initially to be located on chromosome X; however, that location has been determined to correspond to a related pseudogene. Alternatively spliced transcript variants encoding distinct isoforms have been described.

Source: NCBI Gene 3068 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 42 total
• Druggable target: yes
• MANE Select transcript: NM_004494

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4856
Approved symbol	HDGF
Name	heparin binding growth factor
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Aliases	HMG1L2
Ensembl gene	ENSG00000143321
Ensembl biotype	protein_coding
OMIM	600339
Entrez	3068

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000357325, ENST00000368206, ENST00000368209, ENST00000465180, ENST00000469145, ENST00000471377, ENST00000477306, ENST00000482651, ENST00000495212, ENST00000710272

RefSeq mRNA: 6 — MANE Select: NM_004494 NM_001126050, NM_001126051, NM_001319186, NM_001319187, NM_001319188, NM_004494

CCDS: CCDS1156, CCDS44247, CCDS44248

Canonical transcript exons

ENST00000357325 — 6 exons

Exon	Start	End
ENSE00001425593	156751343	156751675
ENSE00001922574	156742109	156743455
ENSE00003510666	156744163	156744348
ENSE00003530257	156743652	156743878
ENSE00003587600	156745008	156745146
ENSE00003591248	156745297	156745373

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 186.0566 / max 1415.8164, expressed in 1828 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15212	155.3059	1828
15211	8.0529	1733
15213	5.2482	1718
15210	3.1834	1411
201759	2.6746	1367
15208	2.6245	1428
15209	2.3497	1302
15218	1.5223	757
15215	1.4206	997
15203	1.4137	836

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	99.47	gold quality
ventricular zone	UBERON:0003053	98.98	gold quality
ganglionic eminence	UBERON:0004023	98.69	gold quality
ileal mucosa	UBERON:0000331	98.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.64	gold quality
mucosa of transverse colon	UBERON:0004991	98.62	gold quality
right uterine tube	UBERON:0001302	98.60	gold quality
tongue squamous epithelium	UBERON:0006919	98.60	gold quality
lower esophagus mucosa	UBERON:0035834	98.58	gold quality
rectum	UBERON:0001052	98.49	gold quality
skin of leg	UBERON:0001511	98.42	gold quality
esophagus mucosa	UBERON:0002469	98.41	gold quality
gastrocnemius	UBERON:0001388	98.37	gold quality
skin of abdomen	UBERON:0001416	98.37	gold quality
metanephros cortex	UBERON:0010533	98.36	gold quality
monocyte	CL:0000576	98.31	gold quality
pancreatic ductal cell	CL:0002079	98.28	gold quality
muscle of leg	UBERON:0001383	98.27	gold quality
mononuclear cell	CL:0000842	98.18	gold quality
embryo	UBERON:0000922	98.15	gold quality
leukocyte	CL:0000738	98.12	gold quality
right lobe of liver	UBERON:0001114	98.05	gold quality
esophagus	UBERON:0001043	98.01	gold quality
zone of skin	UBERON:0000014	97.99	gold quality
gall bladder	UBERON:0002110	97.98	gold quality
duodenum	UBERON:0002114	97.95	gold quality
nasal cavity epithelium	UBERON:0005384	97.93	gold quality
nipple	UBERON:0002030	97.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.90	gold quality
stromal cell of endometrium	CL:0002255	97.84	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	158.03
E-GEOD-76312	yes	155.93
E-ANND-3	yes	11.77
E-MTAB-8271	yes	6.54

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CDH1	Repression
FAS	Activation
SMYD1	Repression
TP53
VEGFA	Activation
VEGFB	Activation
VIM	Activation

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

70 targeting HDGF, 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-4481	100.00	66.42	1669
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-6871-3P	99.43	68.85	741
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-5100	99.11	67.52	1098

Literature-anchored findings (GeneRIF, showing 40)

• Hepatoma-derived growth factor stimulates cell growth after translocation to the nucleus (PMID:11751870)
• may be involved in lung remodeling after injury (PMID:12972397)
• HDGF is a highly expressed vascular endothelial cell protein in vivo and is a potent endothelial mitogen and regulator of endothelial cell migration by mechanisms distinct from VEGF. (PMID:14751852)
• NMR analysis of the hath-domain of human hepatoma-derived growth factor (PMID:15017145)
• HDGF may be a novel prognostic factor for pancreatic ductal carcinoma. (PMID:17062679)
• Hepatoma-derived growth factor expression level was shown to be associated with recurrence and prognosis of squamous cell carcinoma of the esophagus. (PMID:17473954)
• The N-terminal PWWP domain of HDGF is required for DNA binding. HDGF exerts its transcription repressive effect through binding to a conserved DNA element in the promoter of target genes. (PMID:17974029)
• HDGF serves as a template for small ubiquitin-related modifier 1 (SUMO-1) conjugation, although it does not contain a suitable consensus site for SUMOylation. (PMID:18331345)
• HDGF expression is upgraded in postoperative stage I non-small cell lung cancer patients, and is a significantly independent predictive factor. (PMID:18478933)
• HDGF knock-down was found to induce the expression of the pro-apoptotic protein Bad and also inactivate ERK and Akt, which in turn led to dephosphorylation of Bad at Ser-112, Ser-136, and activation of the intrinsic apoptotic pathway. (PMID:18651222)
• Quantitative RT-PCR to study the expression levels of the most interesting gene, HDGF, confirmed that its expression was higher in Ewing sarcoma than in control samples. (PMID:19144156)
• HDGF functions as a transcriptional repressor of the SMYD1 gene through interaction with the transcriptional corepressor CtBP. (PMID:19162039)
• The present study is aimed at examining the role of HDGF in keloid pathogenesis. (PMID:19432814)
• Mechanistic study on growth suppression and apoptosis induction by targeting HDGF in human hepatocellular carcinoma HepG2 cells is reported. (PMID:19710540)
• High hepatoma-derived growth factor is associated with colorectal carcinoma. (PMID:19924574)
• High HDGF expression is associated with poor overall survival in patients with hepatocellular carcinoma. Down-regulation of HDGF inhibits the growth, anchorage-independent growth, migration and invasion of HepG2 cells. (PMID:20846397)
• High HDGF is associated with hilar cholangiocarcinoma. (PMID:20848225)
• Increased nuclear expression of HDGF is a potential unfavourable prognostic factor for patients with hepatoma-derived growth factor (PMID:21255068)
• results suggest that HDGF is involved in cell growth, cell invasion, and apoptosis (PMID:21302807)
• HDGF was highly expressed in 158 non-small cell lung cancer tissues compared with normal control. (PMID:21426662)
• The interactome suggests that HDGF is a multifunctional protein and participates in many cellular events, including ribosome biogenesis, RNA processing, DNA damage repair and transcriptional regulation. (PMID:21907836)
• found that HDGF was overexpressed also in primary gastric, breast, and lung cancer tissues harboring mutant p53 genes (PMID:22006999)
• High hepatoma-derived growth factor is associated with gliomas. (PMID:22037800)
• Hepatoma-derived growth factor regulates breast cancer cell invasion by modulating epithelial–mesenchymal transition. (PMID:22247069)
• Differential proteomic analysis of human glioblastoma and neural stem cells reveals HDGF as a novel angiogenic secreted factor (PMID:22331796)
• Hepatoma-derived growth factor overexpression contributes to the oncogenic processes in oral cancer cells (PMID:22361040)
• Expression of a cytosolic variant of hepatoma-derived growth factor causes a redistribution of nucleolin into the cytoplasm. (PMID:23305559)
• Together, these results indicate that HDGF downregulation participates in POMC-induced suppression of metastasis and EMT in melanoma. (PMID:23468531)
• Up-regulation of hepatoma-derived growth factor facilities tumor progression in malignant melanoma. (PMID:23536873)
• Studied HDGF in gallbladder cancer (GBC).Patients with nuclear HDGF-pos tumors had worse survival than patients with HDGF-negative tumors. Treatment of GBC-SD and SGC-996 lines with HDGF-siRNA significantly reduced the proliferation of GBC cell lines. (PMID:23609195)
• Tumor samples from non-small cell lung cancers show an inverse relationship between microRNA-497 and HDGF levels, and ectopic expression of miR-497 significantly inhibited tumor growth and angiogenesis in a xenograft model (PMID:23673296)
• Patients with higher HDGF and CD31 expression level had poorer overall survival rates. (PMID:23771798)
• Positive expression of HDGF was detected in 46.2 % of patients with extrahepatic cholangiocarcinoma and correlated with poor tumor differentiation. The HDGF expression group had lower survival than the negative HDGF expression group. (PMID:23793608)
• Suggest that HDGF exhibits oncogenic properties and may be a novel prognostic factor in Ewing’s sarcoma. (PMID:23878072)
• The suppressive effect of miR-16 on cell proliferation, colony formation, migration, and invasion is partially mediated by inhibiting HDGF expression. (PMID:23954293)
• Combining p53 expression and HDGF expression significantly improved prognostic stratification for patients with Ewing family tumor. (PMID:24072730)
• expression of HDGF was negatively correlated with miR-141 in gastric cancer tissues: the suppressive effects of miR-141 on GC cell proliferation, colony formation, in vitro migration, and invasion were partially mediated by suppressing HDGF expression. (PMID:24276755)
• HDGF is a potential unfavorable factor for the progression and prognosis of endometrial carcinoma. (PMID:24692842)
• ADAM9 high expression is correlated positively and significantly with HDGF high expression in non-small cell lung cancer. (PMID:24770635)
• Data indicate that hepatoma-derived growth factor (HDGF) was a target of miR-195 in non-small cell lung cancer (NSCLC) cells. (PMID:24891187)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hdgf	ENSMUSG00000004897
rattus_norvegicus	Hdgf	ENSRNOG00000042261

Paralogs (4): HDGFL1 (ENSG00000112273), PSIP1 (ENSG00000164985), HDGFL3 (ENSG00000166503), HDGFL2 (ENSG00000167674)

Protein

Protein identifiers

Hepatoma-derived growth factor — P51858 (reviewed: P51858)

Alternative names: High mobility group protein 1-like 2

All UniProt accessions (3): P51858, A0A384NPW1, A0AA34QVG5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional repressor. Has mitogenic activity for fibroblasts. Heparin-binding protein. Does not have mitogenic activity for fibroblasts. Does not bind heparin. Has mitogenic activity for fibroblasts. Heparin-binding protein.

Subunit / interactions. Monomer, and domain-swapped homodimer. Interacts with nuclear proteins NCL and YBX1/YB1. Interacts with cytoskeletal proteins such as actin, dynein, tubulin and vimentin. Interacts with cytoskeletal proteins such as dynein and tubulin but does not interact with actin or vimentin.

Subcellular location. Nucleus. Cytoplasm. Secreted. Extracellular exosome Nucleus. Extracellular exosome.

Tissue specificity. Ubiquitous.

Post-translational modifications. Sumoylated with SUMO1. Sumoylation prevents binding to chromatin. Phosphorylation at Ser-165 is likely to be required for secretion.

Domain organisation. The PWWP domain harbors the heparin-binding sites and is responsible for DNA-binding, while the C-terminal region is essentially unstructured. The N-terminal region does not contain a typical signal sequence but is required for secretion. It also determines exosomal location.

Similarity. Belongs to the HDGF family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51858-1	1, HDFG-A	yes
P51858-2	2, HDGF-C
P51858-3	3, HDGF-B

RefSeq proteins (6): NP_001119522, NP_001119523, NP_001306115, NP_001306116, NP_001306117, NP_004485* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000313	PWWP_dom	Domain

Pfam: PF00855

UniProt features (45 total): modified residue 10, compositionally biased region 6, binding site 6, strand 6, helix 3, cross-link 2, short sequence motif 2, splice variant 2, chain 1, domain 1, region of interest 1, disulfide bond 1, sequence variant 1, mutagenesis site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1RI0	SOLUTION NMR
2NLU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51858-F1	67.83	0.31

Functional residue map

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

Ligand- & substrate-binding residues (6): 19; 21; 72; 75; 79; 80

Post-translational modifications (12): 44, 132, 133, 165, 184, 199, 200, 202, 206, 239, 80, 80

Disulfide bonds (1): 12–108

Mutagenesis-validated functional residues (1):

Position	Phenotype
165	abolishes secretion and alters location of the protein from inside the exosome to the exosomal surface.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes

MSigDB gene sets: 305 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GNF2_PRDX2, KAAB_FAILED_HEART_ATRIUM_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, MORF_UBE2I, MORF_HDAC1, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOMF_GROWTH_FACTOR_ACTIVITY, GGGTGGRR_PAX4_03, PUJANA_CHEK2_PCC_NETWORK, CTAGGAA_MIR384, MORF_SKP1A, WANG_RESPONSE_TO_BEXAROTENE_UP

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), signal transduction (GO:0007165), protein localization to nucleus (GO:0034504), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of cell division (GO:0051781)

GO Molecular Function (12): nucleotide binding (GO:0000166), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), transcription corepressor binding (GO:0001222), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), actin binding (GO:0003779), growth factor activity (GO:0008083), heparin binding (GO:0008201), tubulin binding (GO:0015631), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), transcription repressor complex (GO:0017053)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
IRE1alpha activates chaperones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
nucleic acid binding	2
cytoskeletal protein binding	2
chromatin organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein localization to organelle	1
positive regulation of DNA-templated transcription	1
positive regulation of cellular process	1
cell division	1
regulation of cell division	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription coregulator binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription coregulator activity	1
receptor ligand activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
transcription regulator complex	1

Protein interactions and networks

STRING

1808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDGF	MDK	P21741	933
HDGF	PTN	P21246	813
HDGF	FGF4	P08620	784
HDGF	FGF17	O60258	771
HDGF	FGF2	P09038	767
HDGF	NUDT6	P53370	762
HDGF	AZU1	P20160	741
HDGF	FGF6	P10767	729
HDGF	FGF8	P55075	717
HDGF	FGF9	P31371	710
HDGF	FGF3	P11487	695
HDGF	DDX5	P17844	673
HDGF	FGF13	Q92913	662
HDGF	NUCLEOLIN	P19338	647
HDGF	YBX1	P16990	646

IntAct

60 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
CPNE2	HIP1	psi-mi:“MI:0914”(association)	0.530
DDX5	HDGF	psi-mi:“MI:0403”(colocalization)	0.510
SSRP1	HDGF	psi-mi:“MI:0403”(colocalization)	0.510
SRSF1	HDGF	psi-mi:“MI:0403”(colocalization)	0.510
HDAC1	HDGF	psi-mi:“MI:0403”(colocalization)	0.510
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
HDGF	PARP1	psi-mi:“MI:0914”(association)	0.460
HDGF		psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
	FER1L5	psi-mi:“MI:0915”(physical association)	0.400
HDGF		psi-mi:“MI:0915”(physical association)	0.400
	HDGF	psi-mi:“MI:0915”(physical association)	0.400
HDGF	GPR37	psi-mi:“MI:0915”(physical association)	0.370
HDGF	XBP1	psi-mi:“MI:0915”(physical association)	0.370
JUN	HDGF	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
EGFL6	CCDC85C	psi-mi:“MI:0914”(association)	0.350
CPNE2	SUPT5H	psi-mi:“MI:0914”(association)	0.350
SH3GL3	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
SH2D3C	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
TRIM24	DDTL	psi-mi:“MI:0914”(association)	0.350

BioGRID (372): HDGF (Affinity Capture-RNA), HDGF (Affinity Capture-RNA), HDGF (Affinity Capture-RNA), HDGF (Affinity Capture-MS), HDGF (Co-fractionation), HDGF (Co-fractionation), HDGF (Reconstituted Complex), HDGF (Proximity Label-MS), HDGF (Proximity Label-MS), HDGF (Proximity Label-MS), HDGF (Affinity Capture-MS), HDGF (Affinity Capture-RNA), HDGF (Affinity Capture-MS), HDGF (Affinity Capture-MS), HDGF (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTU1, A2CG63, A8MW92, D3Z8Y2, F8VPQ2, G3V8T1, O75475, O96028, P29374, P46100, P51858, P51859, Q0VEE6, Q2TB10, Q32N87, Q3TYA6, Q3UMU9, Q4LE39, Q4V9H5, Q5F363, Q5F489, Q5XXA7, Q5XXA9, Q62315, Q66T72, Q6P2L6, Q6P4K1, Q7YQM3, Q7YQM4, Q7Z4V5, Q812D1, Q8BVE8, Q8C9B9, Q8CCG4, Q8CCJ9, Q8MJG1, Q8NFC6, Q8R515, Q8VHK7, Q923W4

Diamond homologs: A4FUF0, F4I907, F4K4D6, O75475, P51858, P51859, Q175F8, Q29NG1, Q32N87, Q3UMU9, Q49A26, Q562D5, Q5R7T2, Q5RKH0, Q5RKN4, Q5XXA9, Q5ZLS7, Q66T72, Q6K431, Q6P2L6, Q6P4K1, Q7Q161, Q7Z4V5, Q812D1, Q8MJG1, Q8MT36, Q8T079, Q8VHK7, Q922P9, Q923W4, Q925G1, Q99JF8, Q9BZ95, Q9FNE4, Q9JMG7, Q9LEY4, Q9LSV0, Q9LYZ0, Q9SF36, Q9SZE1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1197 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156743651:CCT:C	donor_gain	1.0000
1:156743874:GAGTC:G	acceptor_gain	1.0000
1:156743875:AGTC:A	acceptor_gain	1.0000
1:156743876:GTC:G	acceptor_gain	1.0000
1:156743877:TC:T	acceptor_gain	1.0000
1:156743878:CC:C	acceptor_gain	1.0000
1:156743879:C:CC	acceptor_gain	1.0000
1:156743879:CTAG:C	acceptor_loss	1.0000
1:156743880:T:G	acceptor_loss	1.0000
1:156743884:C:CT	acceptor_gain	1.0000
1:156743885:A:T	acceptor_gain	1.0000
1:156743890:C:CT	acceptor_gain	1.0000
1:156743891:A:T	acceptor_gain	1.0000
1:156744159:TTACC:T	donor_loss	1.0000
1:156744160:TACC:T	donor_loss	1.0000
1:156744161:A:AC	donor_gain	1.0000
1:156744161:A:AT	donor_loss	1.0000
1:156744161:ACCT:A	donor_gain	1.0000
1:156744162:C:A	donor_loss	1.0000
1:156744162:C:CC	donor_gain	1.0000
1:156744162:CCT:C	donor_gain	1.0000
1:156744162:CCTC:C	donor_gain	1.0000
1:156744164:T:TA	donor_gain	1.0000
1:156744183:T:A	donor_gain	1.0000
1:156744196:T:A	donor_gain	1.0000
1:156744344:GAGGA:G	acceptor_gain	1.0000
1:156744345:AGGA:A	acceptor_gain	1.0000
1:156744346:GGA:G	acceptor_gain	1.0000
1:156744347:GA:G	acceptor_gain	1.0000
1:156744349:C:CC	acceptor_gain	1.0000

AlphaMissense

1593 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156745045:A:T	I89N	1.000
1:156745054:A:G	L86P	1.000
1:156745057:C:T	G85E	1.000
1:156745058:C:A	G85W	1.000
1:156745058:C:G	G85R	1.000
1:156745058:C:T	G85R	1.000
1:156745065:G:C	F82L	1.000
1:156745065:G:T	F82L	1.000
1:156745066:A:C	F82C	1.000
1:156745066:A:G	F82S	1.000
1:156745067:A:G	F82L	1.000
1:156745074:C:A	R79S	1.000
1:156745074:C:G	R79S	1.000
1:156745075:C:G	R79T	1.000
1:156745123:A:G	L63P	1.000
1:156745123:A:T	L63H	1.000
1:156745144:G:T	A56E	1.000
1:156745300:T:A	E54V	1.000
1:156745304:G:C	H53D	1.000
1:156745306:G:A	T52I	1.000
1:156745307:T:C	T52A	1.000
1:156745309:C:A	G51V	1.000
1:156745309:C:T	G51E	1.000
1:156745310:C:A	G51W	1.000
1:156745310:C:G	G51R	1.000
1:156745310:C:T	G51R	1.000
1:156745311:G:C	F50L	1.000
1:156745311:G:T	F50L	1.000
1:156745312:A:G	F50S	1.000
1:156745313:A:C	F50V	1.000

dbSNP variants (sampled 300 via entrez): RS1000015286 (1:156754306 A>G), RS1000022029 (1:156761183 C>T), RS1000128667 (1:156761686 G>A), RS1000309873 (1:156748671 G>A,C), RS1000536870 (1:156766750 C>T), RS1000713410 (1:156744009 C>T), RS1000930740 (1:156750127 T>G), RS1000978970 (1:156756116 G>A), RS1000997257 (1:156767133 G>A), RS1001025727 (1:156759552 G>A), RS1001253444 (1:156750412 C>T), RS1001254900 (1:156753639 C>T), RS1001858307 (1:156751275 G>A,C,T), RS1001862173 (1:156748791 C>T), RS1001886046 (1:156759942 T>C)

Disease associations

OMIM: gene MIM:600339 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002223_6	HDL cholesterol	2.000000e-08
GCST004232_76	HDL cholesterol levels	3.000000e-08
GCST006585_692	Blood protein levels	3.000000e-23
GCST010002_368	Refractive error	7.000000e-38

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724677 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.31	Kd	4.901	nM	CHEMBL3752910
8.31	ED50	4.901	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 10 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148498: Binding affinity to human HDGF incubated for 45 mins by Kinobead based pull down assay	kd	0.0049	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
sodium arsenite	decreases expression, increases abundance, increases expression	4
Cadmium Chloride	decreases expression, increases expression	3
bisphenol A	increases expression, decreases expression	2
Resveratrol	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Copper	affects binding	2
Doxorubicin	decreases expression, affects expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects localization, increases expression, affects cotreatment	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
afimoxifene	increases expression	1
nickel subsulfide	decreases expression	1
cupric oxide	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
quinocetone	increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651540	Binding	Binding affinity to human HDGF incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2N1	SEES3-1V human HDGF, clone1	Embryonic stem cell	Male
CVCL_A2N2	SEES3-1V human HDGF, clone2	Embryonic stem cell	Male
CVCL_A2N3	SEES3-1V human HDGF, clone3	Embryonic stem cell	Male
CVCL_D1N1	Abcam K-562 HDGF KO	Cancer cell line	Female
CVCL_D2JL	Abcam Raji HDGF KO	Cancer cell line	Male
CVCL_D9WI	Ubigene HT-29 HDGF KO	Cancer cell line	Female
CVCL_UQ68	Abcam Jurkat HDGF KO	Cancer cell line	Male

Clinical trials (associated diseases)

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