VGF

Summary

VGF (VGF nerve growth factor inducible, HGNC:12684) is a protein-coding gene on chromosome 7q22.1, encoding Neurosecretory protein VGF (O15240). Secreted polyprotein that is packaged and proteolytically processed by prohormone convertases PCSK1 and PCSK2 in a cell-type-specific manner.

This gene is specifically expressed in a subpopulation of neuroendocrine cells, and is upregulated by nerve growth factor. The structural organization of this gene is similar to that of the rat gene, and both the translated and the untranslated regions show a high degree of sequence similarity to the rat gene. The encoded secretory protein also shares similarities with the secretogranin/chromogranin family, however, its exact function is not known.

Source: NCBI Gene 7425 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 111 total
• Druggable target: yes
• MANE Select transcript: NM_003378

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12684
Approved symbol	VGF
Name	VGF nerve growth factor inducible
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	SCG7, SgVII
Ensembl gene	ENSG00000128564
Ensembl biotype	protein_coding
OMIM	602186
Entrez	7425

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000249330, ENST00000445482, ENST00000970416

RefSeq mRNA: 1 — MANE Select: NM_003378 NM_003378

CCDS: CCDS5712

Canonical transcript exons

ENST00000249330 — 2 exons

Exon	Start	End
ENSE00000881567	101162509	101164863
ENSE00001108750	101165374	101165569

Expression profiles

Bgee: expression breadth ubiquitous, 105 present calls, max score 95.49.

FANTOM5 (CAGE): breadth broad, TPM avg 42.5802 / max 5507.4326, expressed in 724 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85303	41.8589	722
85301	0.3714	106
85300	0.2877	105
85302	0.0319	10
85299	0.0303	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	95.49	gold quality
hypothalamus	UBERON:0001898	94.98	gold quality
pituitary gland	UBERON:0000007	93.37	gold quality
islet of Langerhans	UBERON:0000006	93.16	gold quality
primary visual cortex	UBERON:0002436	91.42	gold quality
prefrontal cortex	UBERON:0000451	91.29	gold quality
nucleus accumbens	UBERON:0001882	91.09	gold quality
adenohypophysis	UBERON:0002196	90.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.43	gold quality
frontal cortex	UBERON:0001870	90.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.09	gold quality
right frontal lobe	UBERON:0002810	89.57	gold quality
anterior cingulate cortex	UBERON:0009835	88.97	gold quality
cerebral cortex	UBERON:0000956	88.71	gold quality
amygdala	UBERON:0001876	86.69	gold quality
temporal lobe	UBERON:0001871	86.57	gold quality
putamen	UBERON:0001874	86.36	gold quality
brain	UBERON:0000955	84.77	gold quality
central nervous system	UBERON:0001017	84.18	gold quality
Ammon’s horn	UBERON:0001954	82.96	gold quality
caudate nucleus	UBERON:0001873	82.74	gold quality
pancreas	UBERON:0001264	79.09	gold quality
Brodmann (1909) area 10	UBERON:0013541	74.94	gold quality
substantia nigra	UBERON:0002038	74.54	gold quality
cortical plate	UBERON:0005343	73.33	gold quality
body of pancreas	UBERON:0001150	72.80	gold quality
spinal cord	UBERON:0002240	68.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	68.81	gold quality
cerebellar vermis	UBERON:0004720	68.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.98	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	2314.99
E-MTAB-5061	yes	1296.74
E-GEOD-81608	yes	230.17
E-GEOD-83139	yes	141.19
E-ENAD-27	yes	128.80
E-GEOD-81547	yes	28.83
E-HCAD-31	yes	24.98
E-GEOD-93593	yes	15.79
E-ANND-3	yes	4.49
E-MTAB-7303	no	346.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, EGR4, FOS, JUNB, NPAS3, NR4A1, REST, TCF12

miRNA regulators (miRDB)

29 targeting VGF, 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-513A-5P	100.00	69.77	2465
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-4488	95.38	62.00	443
HSA-MIR-4697-5P	95.38	61.72	457
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-1914-3P	95.07	63.37	762
HSA-MIR-503-3P	92.89	66.09	537

Literature-anchored findings (GeneRIF, showing 31)

• Application of neurosecretory protein VGF biomarker model to current diagnostic criteria provides an objective biomarker pattern that identifies patients with amyotrophic lateral sclerosis. (PMID:16481598)
• proVGF-related peptides are present in endocrine cells early during development and adulthood and increase in hyperplasia and tumors (PMID:17440014)
• while Vgf may be a reliable biomarker of progression of muscle weakness in patients with ALS, restoration of Vgf expression in spinal cord motor neurons may therapeutically rescue spinal cord motorneurons against excitotoxic injury (PMID:18432310)
• VGF mRNA levels were significantly reduced in drug-free depressed patients, as compared with controls, and were modulated in response to effective antidepressant treatment. (PMID:20164831)
• localization of neuroendocrine regulatory peptide-1 and-2 (NERP-1 and NERP-2); results suggest that neuroendocrine NERP-1 and NERP-2 might function as local modulatorsin the neuroendocrine system (PMID:20471433)
• VGF is downregulated in bipolar disorder in the CA region of the hippocampus and Brodmann’s area 9 of the prefrontal cortex. (PMID:20631166)
• VGF is regulated by SOD1 and plays a critical role in motor neuron survival (PMID:21151573)
• [review] The vgf gene is induced in vivo by neurotrophins including nerve growth factor (NGF), brain derived growth factor (BDNF) and glial derived growth actor (GDNF), by synaptic activity and by homeostatic and other stimuli. (PMID:21621608)
• The expression of NPY and VGF was increased in the arcuate nucleus, but decreased in the nucleus of the Tractus Solitarius in the brains of type-II diabetic patients. (PMID:22808091)
• results indicate that VGF and PGP9.5 PH are potential biomarkers for ovarian carcinoma (PMID:24086249)
• Among the 19 genes tested, VGF was found to be completely methylated in several Urothelial Cell Carcinoma cell lines (PMID:24830820)
• DISC1 knockdown leads to a reduction of VGF in neurons. (PMID:24934694)
• We conclude that VGF contributes to survival and function of peripheral T cells (PMID:25013207)
• NERPs may be potent endogenous suppressors of glucose-dependent insulin secretion. (PMID:25529453)
• Results indicate that neuron-restrictive silencer factor plays an important role as a repressor of VGF gene regulation in neuroblastoma cells through a mechanism that is dependent on VGF-neuron-restrictive silencer element (PMID:25569790)
• Knock-in mice expressing human VGF were fertile, had increased body weight, whereas those with c-terminal region deletion had reduced adiposity, increased energy expenditure, and improved glucose tolerance. (PMID:25675362)
• Data indicate an increased number of neurosecretory protein VGF-expressing T cells in patients with Alzheimer’s disease (AD) compared to aged healthy controls. (PMID:26142708)
• Data show although no any significant differences between patient groups and lean subjects of proteins SYT4, BAG3, APOA1, and VAV3, except for VGF protein, there was a trend between the expression of these four genes and their protein levels. (PMID:26337083)
• Data show that two VGF peptides (NAPP-19 and QQET-30) were identified in plasma. (PMID:26562304)
• We conclude that some of the already identified variants in VGF from human polymorphism studies may contribute to eating disorders and obesity. (PMID:27088090)
• results suggest VGF enhances dendritic maturation and that these effects can be altered by common SNPs in the VGF gene (PMID:28287464)
• Results show that VGF is epigenetically modified in human non-small-cell lung cancer (NSCLC) tissues if compared to tumor-free lung tissues, which results in an increased transcription and protein expression. (PMID:29209432)
• Serum VGF levels were significantly lower in MDD patients but higher in BD patients compared with HC (both PTukey < 0.01). No correlation was found between serum VGF levels and any data of subjects. (PMID:30575991)
• H19 is a promising prognostic factor in Pancreatic neuroendocrine neoplasms (pNENs) with malignant behaviors and functions as an oncogene via the VGF-mediated PI3K/AKT/CREB pathway. In addition, our study implies that VGF may also serve as a candidate prognostic biomarker and therapeutic target in pNENs. (PMID:31117050)
• Multiscale causal networks identify VGF as a key regulator of Alzheimer’s disease. (PMID:32770063)
• Changes in VGF and C3aR1 gene expression in human adipose tissue in obesity. (PMID:33306149)
• Low VGF is associated with executive dysfunction in patients with major depressive disorder. (PMID:35738161)
• Neuronal survival factor VGF promotes chemoresistance and predicts poor prognosis in lung cancers with neuroendocrine feature. (PMID:35762443)
• Structure of AQEE-30 of VGF Neuropeptide in Membrane-Mimicking Environments. (PMID:36430431)
• Associations of VGF with Neuropathologies and Cognitive Health in Older Adults. (PMID:37177846)
• Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer’s disease. (PMID:38942763)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vgf	ENSMUSG00000037428
rattus_norvegicus	Vgf	ENSRNOG00000001416

Protein

Protein identifiers

Neurosecretory protein VGF — O15240 (reviewed: O15240)

All UniProt accessions (1): O15240

UniProt curated annotations — full annotation on UniProt →

Function. Secreted polyprotein that is packaged and proteolytically processed by prohormone convertases PCSK1 and PCSK2 in a cell-type-specific manner. VGF and peptides derived from its processing play many roles in neurogenesis and neuroplasticity associated with learning, memory, depression and chronic pain. Plays a role in the control of body fluid homeostasis by regulating vasopressin release. Suppresses presynaptic glutamatergic neurons connected to vasopressin neurons. Plays a role in the control of body fluid homeostasis by regulating vasopressin release. Activates GABAergic interneurons which are inhibitory neurons of the nervous system and thereby suppresses presynaptic glutamatergic neurons. Also stimulates feeding behavior in an orexin-dependent manner in the hypothalamus. Functions as a positive regulator for the activation of orexin neurons resulting in elevated gastric acid secretion and gastric emptying. Secreted multifunctional neuropeptide that binds to different cell receptors and thereby plays multiple physiological roles including modulation of energy expenditure, pain, response to stress, gastric regulation, glucose homeostasis as well as lipolysis. Activates the G-protein-coupled receptor C3AR1 via a folding-upon-binding mechanism leading to enhanced lipolysis in adipocytes. Interacts with C1QBP receptor in macrophages and microglia causing increased levels of intracellular calcium and hypersensitivity. Plays a role in the regulation of memory formation and depression-related behaviors potentially by influencing synaptic plasticity and neurogenesis. Induces acute and transient activation of the NTRK2/TRKB receptor and subsequent CREB phosphorylation. Also induces insulin secretion in insulinoma cells by increasing intracellular calcium mobilization. Has bactericidal activity against M.luteus, and antifungal activity against P. Pastoris.

Subunit / interactions. Interacts with HSPA8 on cell membrane. Interacts with C3AR1. Interacts with C1QBP.

Subcellular location. Secreted. Cytoplasmic vesicle. Secretory vesicle.

Tissue specificity. Central and peripheral nervous systems, synthesized exclusively in neuronal and neuroendocrine cells.

Post-translational modifications. Multiple peptides are derived from VGF, with activities in synaptic plasticity, antidepression, penile erection, autonomic activation, and increases in energy expenditure.

RefSeq proteins (1): NP_003369* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026128	VGF	Family

UniProt features (32 total): compositionally biased region 8, sequence conflict 8, peptide 5, modified residue 4, region of interest 3, helix 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9KV8	ELECTRON MICROSCOPY	3.17
7D13	SOLUTION NMR
7D16	SOLUTION NMR
8H0G	SOLUTION NMR
8H0U	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15240-F1	60.87	0.11

Antibody-complex structures (SAbDab): 1 — 9KV8

Functional residue map

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

Post-translational modifications (4): 310, 420, 424, 577

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9031628	NGF-stimulated transcription

MSigDB gene sets: 196 (showing top): ATF_B, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, PAX4_01, GOBP_RESPONSE_TO_COLD, SASAI_TARGETS_OF_CXCR6_AND_PTCH1_UP, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, AP4_Q6, CREBP1_Q2, GOMF_GROWTH_FACTOR_ACTIVITY, USF_C, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING

GO Biological Process (12): ovarian follicle development (GO:0001541), response to dietary excess (GO:0002021), generation of precursor metabolites and energy (GO:0006091), response to cold (GO:0009409), insulin secretion (GO:0030073), response to insulin (GO:0032868), carbohydrate homeostasis (GO:0033500), glucose homeostasis (GO:0042593), defense response to bacterium (GO:0042742), regulation of synaptic plasticity (GO:0048167), response to cAMP (GO:0051591), signal transduction (GO:0007165)

GO Molecular Function (3): hormone activity (GO:0005179), neuropeptide hormone activity (GO:0005184), growth factor activity (GO:0008083)

GO Cellular Component (6): obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), transport vesicle (GO:0030133), cytoplasmic vesicle (GO:0031410), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of proteins	1
Post-translational protein modification	1
Nuclear Events (kinase and transcription factor activation)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
receptor ligand activity	2
cytoplasm	2
endomembrane system	2
female gonad development	1
anatomical structure development	1
response to nutrient levels	1
energy homeostasis	1
metabolic process	1
response to stress	1
response to temperature stimulus	1
protein secretion	1
peptide hormone secretion	1
response to peptide hormone	1
chemical homeostasis	1
carbohydrate homeostasis	1
defense response	1
response to bacterium	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
hormone activity	1
neuropeptide activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
intracellular membrane-bounded organelle	1
cytoplasmic vesicle	1
intracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VGF	BDNF	P23560	807
VGF	NGF	P01138	715
VGF	NPY	P01303	684
VGF	SCG2	P13521	674
VGF	OXT	P01178	667
VGF	CHGB	P05060	653
VGF	NTF3	P20783	631
VGF	ADRB3	P13945	608
VGF	SCG3	Q8WXD2	604
VGF	PCSK1N	Q9UHG2	596
VGF	AGRP	O00253	583
VGF	ADRB1	P08588	581
VGF	POMC	P01189	548
VGF	UCP1	P25874	510
VGF	SCG5	P01164	507

IntAct

43 interactions, top by confidence:

A	B	Type	Score
DKKL1	DENND11	psi-mi:“MI:0914”(association)	0.640
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
NPPA	VGF	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
IFNA6	VGF	psi-mi:“MI:0915”(physical association)	0.400
		psi-mi:“MI:0914”(association)	0.350
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
CHD8	IGLV4-60	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
RIMS1	PSMD12	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
ALK	VGF	psi-mi:“MI:0914”(association)	0.350
IFNE	ACACB	psi-mi:“MI:0914”(association)	0.350
EDDM3A	HS3ST1	psi-mi:“MI:0914”(association)	0.350
IL20	HS3ST1	psi-mi:“MI:0914”(association)	0.350
CGREF1	HS3ST1	psi-mi:“MI:0914”(association)	0.350
DKK3	HS3ST1	psi-mi:“MI:0914”(association)	0.350
NOG	VGF	psi-mi:“MI:0914”(association)	0.350
GCG	VGF	psi-mi:“MI:0914”(association)	0.350
VIP	VGF	psi-mi:“MI:0914”(association)	0.350
PMCH	VGF	psi-mi:“MI:0914”(association)	0.350
IL10	VGF	psi-mi:“MI:0914”(association)	0.350
IFNA10	VGF	psi-mi:“MI:0914”(association)	0.350
PRG3	VGF	psi-mi:“MI:0914”(association)	0.350
NXPH2	VGF	psi-mi:“MI:0914”(association)	0.350
FKBP6	VGF	psi-mi:“MI:0914”(association)	0.350
TSC1	VGF	psi-mi:“MI:0914”(association)	0.350
ACP5	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Synthetic Lethality), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS), VGF (Affinity Capture-MS)

ESM2 similar proteins: A5A6J6, I3L3R5, O15240, O35314, P01214, P01347, P04404, P05059, P05060, P05408, P09681, P10354, P10645, P12272, P13207, P16014, P18844, P20156, P20800, P22858, P23389, P23943, P26339, P27682, P48756, P52211, P54257, P86435, Q06145, Q0VGU4, Q1RMJ9, Q3TVI8, Q5NRP8, Q5RKH6, Q60478, Q62361, Q765Z4, Q765Z5, Q80XD8, Q867D0

Diamond homologs: O15240, P20156, P86435, Q0VGU4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

177 predictions. Top by Δscore:

Variant	Effect	Δscore
7:101164864:C:CC	acceptor_gain	1.0000
7:101164859:GGAGA:G	acceptor_gain	0.9900
7:101164862:GA:G	acceptor_gain	0.9900
7:101164863:AC:A	acceptor_loss	0.9900
7:101164864:CT:C	acceptor_loss	0.9900
7:101164871:A:AC	acceptor_gain	0.9900
7:101164882:C:CT	acceptor_gain	0.9900
7:101165373:CCAG:C	donor_gain	0.9900
7:101164860:GAGA:G	acceptor_gain	0.9800
7:101164861:AGA:A	acceptor_gain	0.9800
7:101164883:A:T	acceptor_gain	0.9800
7:101165447:T:TA	donor_gain	0.9800
7:101164871:A:C	acceptor_gain	0.9700
7:101165317:C:A	donor_gain	0.9700
7:101165519:G:C	donor_gain	0.9700
7:101165368:ATTT:A	donor_loss	0.9600
7:101165369:TTTAC:T	donor_loss	0.9600
7:101165370:TTACC:T	donor_loss	0.9600
7:101165371:TACC:T	donor_loss	0.9600
7:101165372:A:G	donor_loss	0.9600
7:101165373:C:CA	donor_loss	0.9600
7:101165372:A:AC	donor_gain	0.9500
7:101165373:C:CC	donor_gain	0.9500
7:101164861:AGACT:A	acceptor_gain	0.9300
7:101164862:GACTG:G	acceptor_gain	0.9300
7:101164863:ACT:A	acceptor_gain	0.9300
7:101164864:CTG:C	acceptor_gain	0.9300
7:101164860:GAGAC:G	acceptor_gain	0.9200
7:101164865:T:A	acceptor_gain	0.9200
7:101165190:C:A	donor_gain	0.9100

AlphaMissense

3923 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:101163426:A:T	I473N	1.000
7:101163453:A:G	L464P	1.000
7:101163471:A:G	L458P	1.000
7:101163477:A:C	I456S	1.000
7:101163477:A:T	I456N	1.000
7:101163480:A:G	L455P	1.000
7:101163426:A:C	I473S	0.999
7:101163429:A:C	I472S	0.999
7:101163429:A:G	I472T	0.999
7:101163429:A:T	I472N	0.999
7:101163459:A:G	L462P	0.999
7:101163480:A:T	L455H	0.999
7:101163489:A:T	I452N	0.999
7:101163852:A:G	L331P	0.999
7:101164214:C:A	W210C	0.999
7:101164214:C:G	W210C	0.999
7:101163435:A:T	V470D	0.998
7:101163438:A:T	V469E	0.998
7:101163453:A:T	L464Q	0.998
7:101163468:G:A	S459F	0.998
7:101163469:A:G	S459P	0.998
7:101163477:A:G	I456T	0.998
7:101163486:T:A	D453V	0.998
7:101163861:G:T	A328D	0.998
7:101164205:G:C	F213L	0.998
7:101164205:G:T	F213L	0.998
7:101164206:A:G	F213S	0.998
7:101164207:A:G	F213L	0.998
7:101163426:A:G	I473T	0.997
7:101163438:A:C	V469G	0.997

dbSNP variants (sampled 300 via entrez): RS1001211664 (7:101166014 T>C), RS1001503187 (7:101163518 C>G,T), RS1001673007 (7:101169861 T>C), RS1002013828 (7:101171210 G>A,T), RS1002182315 (7:101164973 C>T), RS1002236685 (7:101171680 C>G,T), RS1002269211 (7:101171393 CT>C), RS1002448063 (7:101170975 T>A), RS1002621254 (7:101164726 T>C), RS1003214201 (7:101163268 C>T), RS1003236688 (7:101170185 C>A), RS1003270801 (7:101169857 C>T), RS1003439923 (7:101166500 A>C,G,T), RS1003476928 (7:101166386 G>C,T), RS1003508089 (7:101166029 G>C)

Disease associations

OMIM: gene MIM:602186 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067047 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.65	Kd	2220	nM	CHEMBL3752910
5.65	ED50	2220	nM	CHEMBL3752910
5.58	Kd	2660	nM	CHEMBL5653589
5.58	ED50	2660	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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	2149763: Binding affinity to human VGF incubated for 45 mins by Kinobead based pull down assay	kd	2.2200	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149763: Binding affinity to human VGF incubated for 45 mins by Kinobead based pull down assay	kd	2.6603	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression	4
Valproic Acid	increases expression	3
lead acetate	increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cadmium	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	affects cotreatment, increases expression	2
Tunicamycin	decreases expression, increases expression	2
Cadmium Chloride	increases expression	2
Thapsigargin	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases methylation	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652805	Binding	Binding affinity to human VGF 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

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5CQ	U2OS VGF KO	Cancer cell line	Female

Clinical trials (associated diseases)

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