NGF

Summary

NGF (nerve growth factor, HGNC:7808) is a protein-coding gene on chromosome 1p13.2, encoding Beta-nerve growth factor (P01138). Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems.

This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic neuropathy, type 5 (HSAN5), and dysregulation of this gene’s expression is associated with allergic rhinitis.

Source: NCBI Gene 4803 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary sensory and autonomic neuropathy (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 175 total — 2 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 12 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 30
• Drug target: yes — 5 curated mechanism-of-action drugs
• Constraint (gnomAD): pLI 0.77 (intermediate), LOEUF 0.67 (unconstrained)
• MANE Select transcript: NM_002506
• Interaction hub: 3,605 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7808
Approved symbol	NGF
Name	nerve growth factor
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134259
Ensembl biotype	protein_coding
OMIM	162030
Entrez	4803

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 17 protein_coding

MANE Select: ENST00000369512

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000369512, ENST00000675637, ENST00000676038, ENST00000679806, ENST00000680116, ENST00000680540, ENST00000680752, ENST00000681124, ENST00000871201, ENST00000871202, ENST00000871203, ENST00000871204, ENST00000871205, ENST00000929056, ENST00000970250, ENST00000970251, ENST00001144351

RefSeq mRNA: 2 — MANE Select: NM_002506 NM_001437545, NM_002506

CCDS: CCDS882

Canonical transcript exons

ENST00000369512 — 3 exons

Exon	Start	End
ENSE00001020911	115338204	115338249
ENSE00001020912	115293627	115293750
ENSE00001450208	115285917	115286807

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 94.67.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2617 / max 74.0482, expressed in 766 samples.

Highest expression (Bgee): cartilage tissue, uterine tube, ovary, atrium auricular region, apex of heart.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NGF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.3e-40	-0.57	1:115330730:TCACTC:T
Lung	eqtl	4.0e-08	+0.69	1:115318998:A:G
Artery Tibial	eqtl	5.6e-05	+0.47	1:115139732:G:A
Artery Aorta	eqtl	5.8e-04	+0.52	1:115139732:G:A
Testis	eqtl	1.1e-03	-0.17	1:115287322:C:A
Thyroid	eqtl	7.7e-03	+0.75	1:115265312:C:T
Adipose Subcutaneous	eqtl	1.3e-02	-0.79	1:114861566:C:T
Skin Sun Exposed Lower leg	eqtl	2.1e-02	+0.28	1:115343462:C:T
Brain Caudate basal ganglia	eqtl	2.1e-02	+0.57	1:115799036:C:A
Adipose Visceral Omentum	eqtl	3.0e-02	+0.15	1:115177624:G:C
Brain Cortex	eqtl	3.4e-02	+0.30	1:116197828:C:A
Colon Transverse	eqtl	4.6e-02	+0.10	1:115177645:A:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
13980	3.1546	749
13981	0.1071	44

Top tissues by expression

showing 100 of 282 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	94.67	gold quality
left uterine tube	UBERON:0001303	86.55	gold quality
right ovary	UBERON:0002118	86.05	gold quality
right atrium auricular region	UBERON:0006631	86.05	gold quality
apex of heart	UBERON:0002098	85.58	gold quality
cardiac atrium	UBERON:0002081	85.09	gold quality
ascending aorta	UBERON:0001496	85.04	gold quality
left ovary	UBERON:0002119	84.87	gold quality
thoracic aorta	UBERON:0001515	84.86	gold quality
aorta	UBERON:0000947	83.68	gold quality
tibial artery	UBERON:0007610	82.92	gold quality
popliteal artery	UBERON:0002250	82.90	gold quality
heart left ventricle	UBERON:0002084	81.87	gold quality
omental fat pad	UBERON:0010414	81.82	gold quality
peritoneum	UBERON:0002358	81.79	gold quality
cardiac ventricle	UBERON:0002082	81.78	gold quality
heart	UBERON:0000948	81.49	gold quality
ovary	UBERON:0000992	81.15	gold quality
descending thoracic aorta	UBERON:0002345	81.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.62	gold quality
left coronary artery	UBERON:0001626	80.42	gold quality
coronary artery	UBERON:0001621	79.62	gold quality
vena cava	UBERON:0004087	78.69	silver quality
myocardium	UBERON:0002349	78.65	gold quality
body of uterus	UBERON:0009853	78.62	gold quality
right coronary artery	UBERON:0001625	77.92	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.49	gold quality
tibial nerve	UBERON:0001323	76.48	gold quality
left ventricle myocardium	UBERON:0006566	74.15	gold quality
endocervix	UBERON:0000458	74.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	73.97	gold quality
pericardium	UBERON:0002407	73.92	silver quality
inferior olivary complex	UBERON:0002127	73.84	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	73.49	gold quality
mucosa of stomach	UBERON:0001199	73.48	gold quality
cardiac muscle of right atrium	UBERON:0003379	73.42	gold quality
myometrium	UBERON:0001296	73.32	gold quality
biceps brachii	UBERON:0001507	72.51	gold quality
lateral nuclear group of thalamus	UBERON:0002736	72.45	gold quality
triceps brachii	UBERON:0001509	72.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.16	gold quality
adipose tissue	UBERON:0001013	71.69	gold quality
gluteal muscle	UBERON:0002000	71.57	gold quality
connective tissue	UBERON:0002384	71.43	gold quality
saphenous vein	UBERON:0007318	71.26	silver quality
ectocervix	UBERON:0012249	71.23	gold quality
body of tongue	UBERON:0011876	71.09	gold quality
sigmoid colon	UBERON:0001159	70.62	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.15	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.13	gold quality
nipple	UBERON:0002030	69.84	gold quality
right lobe of liver	UBERON:0001114	69.73	gold quality
subthalamic nucleus	UBERON:0001906	69.62	gold quality
lower esophagus muscularis layer	UBERON:0035833	69.38	gold quality
lower esophagus	UBERON:0013473	69.29	gold quality
smooth muscle tissue	UBERON:0001135	69.22	gold quality
medulla oblongata	UBERON:0001896	69.13	gold quality
tongue	UBERON:0001723	69.08	gold quality
germinal epithelium of ovary	UBERON:0001304	68.99	silver quality
right lobe of thyroid gland	UBERON:0001119	68.88	gold quality
inferior vagus X ganglion	UBERON:0005363	68.71	gold quality
medial globus pallidus	UBERON:0002477	68.50	gold quality
cardia of stomach	UBERON:0001162	68.49	gold quality
dorsal plus ventral thalamus	UBERON:0001897	68.45	gold quality
trabecular bone tissue	UBERON:0002483	68.41	gold quality
pons	UBERON:0000988	68.40	gold quality
metanephros cortex	UBERON:0010533	67.99	gold quality
superior surface of tongue	UBERON:0007371	67.96	gold quality
substantia nigra pars reticulata	UBERON:0001966	67.79	gold quality
synovial joint	UBERON:0002217	67.79	gold quality
ventral tegmental area	UBERON:0002691	67.78	gold quality
spleen	UBERON:0002106	67.75	gold quality
substantia nigra pars compacta	UBERON:0001965	67.66	gold quality
female reproductive system	UBERON:0000474	67.56	gold quality
olfactory bulb	UBERON:0002264	67.52	gold quality
islet of Langerhans	UBERON:0000006	67.43	gold quality
pylorus	UBERON:0001166	67.39	gold quality
trigeminal ganglion	UBERON:0001675	67.32	gold quality
layer of synovial tissue	UBERON:0007616	67.27	gold quality
left lobe of thyroid gland	UBERON:0001120	67.23	gold quality
renal medulla	UBERON:0000362	67.10	gold quality
pharyngeal mucosa	UBERON:0000355	67.05	gold quality
penis	UBERON:0000989	66.83	gold quality
decidua	UBERON:0002450	66.81	gold quality
superior vestibular nucleus	UBERON:0007227	66.78	gold quality
urethra	UBERON:0000057	66.74	gold quality
right adrenal gland	UBERON:0001233	66.67	gold quality
trachea	UBERON:0003126	66.67	gold quality
fundus of stomach	UBERON:0001160	66.38	gold quality
left adrenal gland	UBERON:0001234	66.36	gold quality
epithelium of esophagus	UBERON:0001976	66.36	gold quality
esophagus squamous epithelium	UBERON:0006920	66.28	gold quality
left adrenal gland cortex	UBERON:0035825	66.24	gold quality
adrenal cortex	UBERON:0001235	66.19	gold quality
superficial temporal artery	UBERON:0001614	65.88	gold quality
squamous epithelium	UBERON:0006914	65.87	gold quality
thyroid gland	UBERON:0002046	65.68	gold quality
secondary oocyte	CL:0000655	65.56	gold quality
cauda epididymis	UBERON:0004360	65.56	silver quality
vagina	UBERON:0000996	65.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.18

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Ovary	tissue	15.9
Spinal cord	tissue	6.9
Heart muscle	tissue	5.7
Frontal cortex	tissue	5.6
Vagina	tissue	5.0
Urinary bladder	tissue	4.0
Smooth muscle	tissue	3.7
Hippocampal formation	tissue	3.1
Endometrium 1	tissue	2.9
Pituitary gland	tissue	2.8
Cerebral cortex	tissue	2.8
Somatosensory cortex	tissue	2.8
Temporal cortex	tissue	2.6
Adipose tissue	tissue	2.4
Fallopian tube	tissue	2.4
Caudate putamen	tissue	2.4
Choroid plexus	tissue	2.3
Entorhinal cortex	tissue	2.2
Retrosplenial and cingulate cortex	tissue	2.2
Prefrontal cortex	tissue	2.1
Motor cortex	tissue	2.1
Spleen	tissue	2.1
Salivary gland	tissue	2.0
Amygdala	tissue	2.0
Retrosplenial cortex	tissue	1.7
Insular cortex	tissue	1.7
Gallbladder	tissue	1.6
Ventral forebrain	tissue	1.6
Occipital cortex	tissue	1.6
Appendix	tissue	1.5
Cervix	tissue	1.4
Medulla oblongata	tissue	1.4
Epididymis	tissue	1.3
Liver	tissue	1.3
Adrenal gland	tissue	1.2
Hippocampus	tissue	1.1
Postcentral gyrus	tissue	1.1
Pons	tissue	1.0
Seminal vesicle	tissue	1.0
Tongue	tissue	1.0
Placenta	tissue	1.0
Kidney	tissue	1.0
Locus coeruleus	tissue	1.0
Superior colliculi	tissue	0.9
Colon	tissue	0.8
Olfactory bulb	tissue	0.8
Septum	tissue	0.8
Esophagus	tissue	0.7
Nucleus accumbens	tissue	0.7
Substantia nigra	tissue	0.7
Lung	tissue	0.7
Prostate	tissue	0.7
Testis	tissue	0.6
Midbrain	tissue	0.6
Thalamus	tissue	0.6
Hypothalamus	tissue	0.6
Lymph node	tissue	0.5
Rectum	tissue	0.5
Basal ganglia	tissue	0.5
Putamen	tissue	0.5

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (18.4), Ventral spinal cord (6.9), Dorsal spinal cord (3.1), Ventral hippocampus (3.1), Mammillary body (2.6).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets:

Target	Regulation
CDKN1A	Activation
CTSS	Activation
GCH1	Activation
SCN9A	Activation

Upstream regulators (CollecTRI, top): AP1, AR, ASCL1, CEBPD, CREB1, CREM, CUX1, DNMT3B, EGR1, EGR3, EGR4, FOS, HAND1, HES1, ID2, ID3, ING4, JUN, JUNB, JUND, KLF7, LRRFIP1, NEUROD6, NFATC4, NFE2L2, NFKB2, NFKB, NR1H4, NR4A1, NR4A2, NR5A1, NRG1, POU2F2, POU4F1, RARB, RELA, SP1, TFAP2A, TP53, VDR

miRNA regulators (miRDB)

Targeting NGF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 37 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-32-3P	99.36	68.20	2517

Functional genomics

gnomAD constraint: pLI 0.769, LOEUF 0.67, missense Z 1.24 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000369512 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:115,286,073–115,286,495	132 / 189.2	0.70	no
1:115,286,496–115,286,795	151 / 141.6	1.07	no

Literature-anchored findings (GeneRIF, showing 40)

• On immunologic stimuli, human eosinophils secrete nerve growth factor that promotes elongation of neurites. (PMID:11877300)
• Results support the involvement of NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome, implying neuroimmune and adipoimmune pathways in the pathobiology of these cardiovascular disorders. (PMID:11935372)
• Phenotypic knockout of nerve growth factor (NGF) activity in transgenic anti-NGF mice (AD11 mice) results in a progressive neurodegenerative phenotype. (PMID:12205295)
• The gene expression of this protein was studied in the developing human tooth. (PMID:12397373)
• correlation between the activity of systemic lupus erythematosus and the levels of NGF in serum (PMID:12453472)
• NGF modulates cytokine mRNA expression in immune cells. (NGF) (PMID:12531456)
• Interleukin-10 and nerve growth factor have reciprocal upregulatory effects on intestinal epithelial cells. (PMID:12676754)
• Data suggest that activation of bronchial eosinophils by neurotrophins (nerve growth factor, brain-derived neurotrophic factor, neurotrophins-3 and -4) might play a role in the regulation of eosinophilic inflammation in allergic asthma. (PMID:12900521)
• Circulating levels in Behcet disease are not different from normal values. (PMID:12918708)
• histamine may enhance nerve growth factor production by inducing c-Fos expression in keratinocytes. (PMID:12925217)
• NGF might have a crucial role in the auditory pathway, promoting the survival and preventing the degeneration of sensorineural cells. (PMID:14587217)
• NGF is expressed in human pancreatic beta cells and modulates insulin secretion through a paracrine/autocrine loop, similar to the one observed in cultured rat beta cells (PMID:14708938)
• Zinc(II) in native beta-NGF plays an important role in the structure and the biological activity of the protein (PMID:14970904)
• mutation causes loss of pain perception (PMID:14976160)
• acts as a co-receptor and molecular switch governing the p75NTR-mediated pro-apoptotic signal induced by proNGF (PMID:14985763)
• determined the 2.4 A crystal structure of NGF complexed with the extracellular domain of p75; the complex is composed of an NGF homodimer asymmetrically bound to a single p75 (PMID:15131306)
• expression of NGF and its receptors, TrkA and p75NTR, in hepatocellular carcinomas (HCC); NGF and its receptors are thought to have a role in cellular interactions involving HCC cells, hepatic stellate cells, arterial cells and nerve cells in HCC tissues (PMID:15523689)
• Monocytes, produce, store and release NGF, brain-derived neurotrophic factor and neurotrophin 3 (PMID:15544837)
• pro-NGF purified from AD human brains can induce apoptosis in neuronal cell cultures through its interaction with the p75NTR receptor (PMID:15681836)
• NGF is indeed involved in growth initiation of human primordial follicles. (PMID:15829579)
• p62 regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination (PMID:16079148)
• NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels (PMID:16319926)
• Overexpression in salivary adenoid cystic carcinoma may constitute a reason for perineural invasion (PMID:16546643)
• Light and electron microscopy immunohistochemistry showed that tonsillar samples were positive for NGF. (PMID:16786155)
• Here, we show the first evidence of NGF-TrkA autocrine loop and clinical significance of Nerve growth factor(NGF)overexpression in oesophageal squamous cell carcinoma(OESCC). (PMID:16832412)
• non-fat cells in human adipose tissue contribute to most of the release of NGF seen during primary culture of adipose tissue explants from obese women (PMID:16839849)
• Findings report, for the first time, the expression pattern of NGF and TrkA proteins in human scalp skin and hair follicle. (PMID:16919030)
• SNP associated with ADHD in the 5’ pro-NGF sequence may affect intracellular processing and secretion of NGF. (PMID:17192954)
• a NGF/BEX2/NF-kappaB pathway is involved in regulating apoptosis in breast cancer cells and in modulating response to tamoxifen in primary tumors (PMID:17638883)
• We show here high expression of TRKA in Hodgkin-Reed/Sternberg cell lines as compared to normal B cells and other B cell lymphomas, without major increases in TRKA gene dosage. (PMID:17673289)
• has mitogenic and motogenic effects on oral mucosal keratinocytes. Differential expression throughout the epithelium suggests a role in epithelial differentiation (PMID:17850422)
• Nerve growth factor was only detected in liver tissue with hepatocellular carcinoma present. (PMID:17854142)
• NGF concentration in CSF is a useful marker of brain damage following severe TBI (PMID:17881264)
• Late preweaning exposure of rats to chlorpyrifos and methyl parathion affect expression of nerve growth factor in hippocampus and cerebral cortex. (PMID:17893397)
• The NGF mRNA levels at baseline in the interstitial cystitis patients were significantly greater than those in the controls. NGF expression plays an important role in the pathogenesis of IC. (PMID:17905097)
• These results newly demonstrate the cardiac prosurvival action of NGF and provide mechanistic information on the signaling pathway (PMID:17992191)
• These data support a role for NGF-induced cell apoptosis in LLS formation in vitro. (PMID:18068123)
• N-terminal Vps10p domain of sortilin, which is responsible for the interaction with the neurotrophins, adopts a beta-propeller fold, and that the N-terminal regions of sortilin, pro-NGF and pro-BDNF are mainly intrinsically disordered regions (PMID:18191449)
• Targeting NGF in breast cancer may have therapeutic ramifications. (PMID:18199526)
• Variants in NGFB gene appear to modify the risk conferred by the NTRK3 rs7180942 risk genotypes showing a synergistic epistatic interaction. (PMID:18203754)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ngfb	ENSDARG00000014050
danio_rerio	ngfa	ENSDARG00000058961
mus_musculus	Ngf	ENSMUSG00000027859
rattus_norvegicus	Ngf	ENSRNOG00000016571

Paralogs (3): BDNF (ENSG00000176697), NTF3 (ENSG00000185652), NTF4 (ENSG00000225950)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97321) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 39 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sensory neuron innervation pattern	2
decreased body size	2
abnormal myocardial fiber morphology	1
tremors	1
abnormal dorsal root ganglion morphology	1
abnormal sympathetic ganglion morphology	1
superior cervical ganglion hypertrophy	1
absent superior cervical ganglion	1
small superior cervical ganglion	1
trigeminal ganglion hypertrophy	1
decreased body weight	1
delayed eyelid opening	1
blepharoptosis	1
abnormal gait	1
abnormal object recognition memory	1
postnatal growth retardation	1
edema	1
abnormal pain threshold	1
abnormal hair growth	1
premature death	1
abnormal innervation	1
thin myocardium	1
dilated heart left ventricle	1
dilated heart right ventricle	1
dilated cardiomyopathy	1

+14 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Helarctos malayanus	O18753	100.0%	Diamond
Procyon lotor	O18755	100.0%	Diamond
Ailurus fulgens	O97759	100.0%	Diamond
Bothrops cotiara	P0DMG7	100.0%	Diamond
Sus scrofa	P14082	100.0%	Diamond
Naja atra	P61898	100.0%	Diamond
Naja kaouthia	P61899	100.0%	Diamond
Macaca mulatta	Q06225	100.0%	Diamond
Equus caballus	Q0EAB7	100.0%	Diamond
Loxocemus bicolor	Q1HN33	100.0%	Diamond
Eryx colubrinus colubrinus	Q1HN34	100.0%	Diamond
Eryx johnii	Q1KN12	100.0%	Diamond
Eryx conicus	Q1X6Y1	100.0%	Diamond
Sanzinia madagascariensis	Q1X6Y8	100.0%	Diamond
Acrantophis dumerili	Q1X6Y9	100.0%	Diamond
Morelia spilota	Q1X703	100.0%	Diamond
Candoia carinata	Q1X707	100.0%	Diamond
Eunectes notaeus	Q1X709	100.0%	Diamond
Epicrates cenchria	Q1X710	100.0%	Diamond
Ursus thibetanus	Q3SAT7	100.0%	Diamond
Spermophilus citellus	Q4L0Y3	100.0%	Diamond
Pan troglodytes	Q5IS78	100.0%	Diamond
Ailuropoda melanoleuca	Q6LCI5	100.0%	Diamond
Canis lupus familiaris	Q7YRB4	100.0%	Diamond
Bos taurus	Q95106	100.0%	Diamond
Demansia vestigiata	A6MFL5	99.6%	Diamond
Ursus arctos	O18752	99.6%	Diamond
Lichanura trivirgata	Q1HN31	99.6%	Diamond
Chilabothrus striatus	Q1HN42	99.6%	Diamond
Charina bottae	Q1X6Z6	99.6%	Diamond
Boa constrictor	Q1X708	99.6%	Diamond
Oxyuranus microlepidotus	Q3HXZ0	99.6%	Diamond
Xenopeltis unicolor	Q1HN38	99.5%	Diamond
Cylindrophis ruffus	Q1X701	99.5%	Diamond
Corallus caninus	Q1X711	99.5%	Diamond
Pseudechis australis	Q3HXY1	99.2%	Diamond
Notechis scutatus scutatus	Q3HXY6	99.2%	Diamond
Oxyuranus scutellatus scutellatus	Q3I5F4	99.2%	Diamond
Gorilla gorilla gorilla	Q9N2F0	99.2%	Diamond
Cavia porcellus	O70183	99.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01765	ncRNA	105378916
NGF-AS1	ncRNA	112840934
SYCP1	protein-coding	6847
TSHB	protein-coding	7252
TSPAN2	protein-coding	10100

Protein

Protein identifiers

Beta-nerve growth factor — P01138 (reviewed: P01138)

All UniProt accessions (2): A0A7P0TAZ6, P01138

UniProt curated annotations — full annotation on UniProt →

Function. Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival. The immature NGF precursor (proNGF) functions as a ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse. In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro). Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI. Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer. The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form.

Subunit / interactions. Homodimer. The homodimer interacts with a single NTRK1 chain. The homodimer interacts with a single NGFR chain. The NGF dimer interacts with a single SORCS2 chain (via extracellular domain). The NGF precursor (proNGF) binds to a receptor complex formed by SORT1 and NGFR, which leads to NGF endocytosis. Both mature NGF and the immature NGF precursor (proNGF) interact with SORCS2 and with the heterodimer formed by SORCS2 and NGFR (via extracellular domains). The NGF precursor (proNGF) has much higher affinity for SORCS2 than mature NGF. The NGF precursor (proNGF) has much higher affinity for SORT1 than mature NGF. Interacts with ADAM10 in a divalent cation-dependent manner. Interaction with SORCS3.

Subcellular location. Secreted. Endosome lumen.

Disease relevance. Neuropathy, hereditary sensory and autonomic, 5 (HSAN5) [MIM:608654] A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the NGF-beta family.

RefSeq proteins (2): NP_001424474, NP_002497* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002072	Nerve_growth_factor-rel	Domain
IPR019846	Nerve_growth_factor_CS	Conserved_site
IPR020408	Nerve_growth_factor-like	Family
IPR020425	Nerve_growth_factor_bsu	Family
IPR020437	Nerve_growth_factor_bsu_mml	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00243

UniProt features (31 total): strand 9, sequence variant 6, disulfide bond 3, binding site 3, sequence conflict 2, turn 2, glycosylation site 2, signal peptide 1, propeptide 1, helix 1, chain 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
9TPP	Antibody-antigen complex	X-RAY DIFFRACTION	1.8
1WWW	NGF IN COMPLEX WITH DOMAIN 5 OF THE TRKA RECEPTOR	X-RAY DIFFRACTION	2.2
1SG1	Crystal Structure of the Receptor-Ligand Complex between Nerve Growth Factor and the …	X-RAY DIFFRACTION	2.4
9TQ6	Antibody-antigen complex	X-RAY DIFFRACTION	2.4
4ZBN	Non-helical DNA Triplex Forms a Unique Aptamer Scaffold for High Affinity Recognition of …	X-RAY DIFFRACTION	2.45
4EDW	Nerve Growth Factor in Complex with Fab from humanized version of mouse mAb 911 …	X-RAY DIFFRACTION	2.48
4EDX	Nerve Growth Factor in Complex with Fab from mouse mAb 911	X-RAY DIFFRACTION	2.5
2IFG	Structure of the extracellular segment of human TRKA in complex with nerve growth factor	X-RAY DIFFRACTION	3.4
5JZ7	NGF IN COMPLEX WITH MEDI578 scFv	X-RAY DIFFRACTION	3.4
6YW8	NMR solution structure of unbound recombinant human Nerve Growth Factor (rhNGF)	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01138-F1	73.55	0.37

Antibody-complex structures (SAbDab)

5 antibodies co-crystallized with this protein: 4EDW, 4EDX, 5JZ7, LUVAGROBART, TANEZUMAB

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

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 (3)

Position	Role
173	a 1-acyl-sn-glycero-3-phospho-(1D-myo-inositol)
209	a 1-acyl-sn-glycero-3-phospho-(1D-myo-inositol)
209	a 1-acyl-sn-glycero-3-phospho-L-serine

Disulfide bonds (3)

Type	Positions
Disulfide bond	189–231, 136–201, 179–229

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	69, 114

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 32; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

32 pathways:

ID	Pathway	Evidence
R-HSA-209563	Axonal growth stimulation	curated
R-HSA-205025	NADE modulates death signalling	curated
R-HSA-209560	NF-kB is activated and signals survival	curated
R-HSA-205017	NFG and proNGF binds to p75NTR	curated
R-HSA-170984	ARMS-mediated activation	electronic
R-HSA-187015	Activation of TRKA receptors	—
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE	—
R-HSA-193681	Ceramide signalling	electronic
R-HSA-73887	Death Receptor Signaling	—
R-HSA-9036866	Expression and Processing of Neurotrophins	—
R-HSA-170968	Frs2-mediated activation	electronic
R-HSA-167060	NGF processing	electronic
R-HSA-193648	NRAGE signals death through JNK	electronic
R-HSA-205043	NRIF signals cell death from the nucleus	electronic
R-HSA-198203	PI3K/AKT activation	electronic
R-HSA-167021	PLC-gamma1 signalling	electronic
R-HSA-169893	Prolonged ERK activation events	—
R-HSA-177504	Retrograde neurotrophin signalling	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-187037	Signaling by NTRK1 (TRKA)	—
R-HSA-166520	Signaling by NTRKs	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-187687	Signalling to ERKs	—
R-HSA-167044	Signalling to RAS	electronic
R-HSA-198745	Signalling to STAT3	electronic
R-HSA-187706	Signalling to p38 via RIT and RIN	electronic
R-HSA-187042	TRKA activation by NGF	electronic
R-HSA-193704	p75 NTR receptor-mediated signalling	—
R-HSA-193670	p75NTR negatively regulates cell cycle via SC1	electronic
R-HSA-209543	p75NTR recruits signalling complexes	electronic
R-HSA-193697	p75NTR regulates axonogenesis	—
R-HSA-193639	p75NTR signals via NF-kB	—

MSigDB gene sets: 415 (showing top): PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_CIRCADIAN_RHYTHM, REACTOME_RETROGRADE_NEUROTROPHIN_SIGNALLING, MODULE_92, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_CELL_MATURATION, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEURON_PROJECTION_EXTENSION, MODULE_255, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, LFA1_Q6, KEGG_MAPK_SIGNALING_PATHWAY

GO Biological Process (16): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), circadian rhythm (GO:0007623), negative regulation of cell population proliferation (GO:0008285), extrinsic apoptotic signaling pathway via death domain receptors (GO:0008625), positive regulation of gene expression (GO:0010628), nerve development (GO:0021675), nerve growth factor signaling pathway (GO:0038180), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of neuron differentiation (GO:0045666), positive regulation of Ras protein signal transduction (GO:0046579), neurotrophin TRK receptor signaling pathway (GO:0048011), neuron projection morphogenesis (GO:0048812), modulation of chemical synaptic transmission (GO:0050804), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of ERK1 and ERK2 cascade (GO:0070374), signal transduction (GO:0007165)

GO Molecular Function (9): nerve growth factor receptor binding (GO:0005163), growth factor activity (GO:0008083), metalloendopeptidase inhibitor activity (GO:0008191), lipid binding (GO:0008289), transmembrane receptor protein tyrosine kinase activator activity (GO:0030297), enzyme inhibitor activity (GO:0004857), signaling receptor binding (GO:0005102), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (5): extracellular region (GO:0005576), Golgi lumen (GO:0005796), cytosol (GO:0005829), synaptic vesicle (GO:0008021), endosome lumen (GO:0031904)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Signaling by NTRK1 (TRKA)	4
Cell death signalling via NRAGE, NRIF and NADE	3
p75 NTR receptor-mediated signalling	3
Signalling to ERKs	2
Prolonged ERK activation events	2
p75NTR signals via NF-kB	2
Expression and Processing of Neurotrophins	1
Activation of TRKA receptors	1
p75NTR regulates axonogenesis	1

GO top-level categories

showing 60 of 61 GO namespaces:

Category	Terms
neurotrophin signaling pathway	2
binding	2
cellular anatomical structure	2
intracellular organelle lumen	2
enzyme-linked receptor protein signaling pathway	1
rhythmic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
extrinsic apoptotic signaling pathway	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
nervous system development	1
animal gross anatomical part developmental process	1
cellular response to nerve growth factor stimulus	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
death receptor binding	1
neurotrophin receptor binding	1
receptor ligand activity	1
metalloendopeptidase activity	1
endopeptidase inhibitor activity	1
transmembrane receptor protein tyrosine kinase activity	1
protein tyrosine kinase activator activity	1
signaling receptor activator activity	1
catalytic activity	1
enzyme regulator activity	1
molecular function inhibitor activity	1
protein binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
Golgi apparatus	1
cytoplasm	1
exocytic vesicle	1
presynapse	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
extrinsic apoptotic signaling pathway via death domain receptors	BP	direct assay
neuron projection morphogenesis	BP	direct assay
positive regulation of gene expression	BP	mutant phenotype
metalloendopeptidase inhibitor activity	MF	direct assay
nerve growth factor receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 3,605 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NGF	NTRK1	P04629	967
NGF	NGFR	P08138	965
NGF	NTRK2	Q16620	934
NGF	GDNF	P39905	920
NGF	NTRK3	Q16288	902
NGF	CNTF	P26441	864
NGF	TAC1	P20366	859
NGF	EGF	P01133	851
NGF	TRPV1	Q8NER1	839
NGF	KNG1	P01042	815
NGF	AKT1	P31749	809
NGF	TH	P07101	806
NGF	TRPA1	O75762	798
NGF	GAP43	P17677	794
NGF	FGF2	P09038	789

IntAct

Human interaction partners of NGF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
SORT1	direct interaction	0.680	5
NTRK1	direct interaction	0.680	3
APP	physical association	0.560	9
EIF2S2	physical association	0.560	3
NGFR	direct interaction	0.540	2
SORCS3	direct interaction	0.440	3

BioGRID (19 interactions; top human partners by supporting records): NTRK1 (Reconstituted Complex; 4 records), SORT1 (Reconstituted Complex; 3 records), NGFR (Reconstituted Complex; 2 records), A2M (Reconstituted Complex), CHRM4 (Affinity Capture-Western), CRYAB (Protein-peptide), ITGA9 (Reconstituted Complex), ITGB1 (Reconstituted Complex), LRP1 (Reconstituted Complex)

SIGNOR signaling

showing 5 of 6 signaling interactions:

A	Effect	B	Mechanism
NGF	up-regulates	NGFR	binding
THBS1	up-regulates	NGF	binding
NGF	up-regulates	NTRK1	binding
NGF	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
NGF	“up-regulates quantity by expression”	SCN9A	“transcriptional regulation”

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ NGF-NGFR-SORT1 complex	3	NGF, NGFR, SORT1
★ CHRM4-NGF complex	2	CHRM4, NGF
★ NGF-NTRK1 complex	2	NGF, NTRK1
★ NGF-NGFR complex	2	NGF, NGFR

Ligand–receptor pairs (CellPhoneDB) (3)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
NTRK1	ligand	Signaling by Beta-nerve growth factor
SORT1	ligand	Signaling by Beta-nerve growth factor
NGFR	ligand	Signaling by Beta-nerve growth factor

Disease & clinical

Genetic variants

Variant evidence for NGF: 175 ClinVar records (3 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 15 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	99
Likely benign	51
Benign	8

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
14045	NM_002506.3(NGF):c.661C>T (p.Arg221Trp)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
29802	NM_002506.3(NGF):c.680_682delinsA (p.Thr227fs)	Pathogenic	criteria provided, single submitter	2
2181214	NM_002506.3(NGF):c.241C>T (p.Arg81Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore NGF’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 466):

Position(s)	Effect	Δscore	Sites
1:115338202–115338203	donor_loss	0.9900	5
1:115338202	donor_loss	0.9800
1:115286808–115286809	acceptor_loss	0.9700	6
1:115338199	donor_loss	0.9600
1:115293751–115293752	acceptor_loss	0.9400	6
1:115294599	donor_gain	0.9400
1:115293753	acceptor_loss	0.9300
1:115338214	donor_gain	0.9300
1:115293625–115293626	donor_loss	0.9200	5
1:115335986	donor_gain	0.9200

AlphaMissense

539 missense substitutions predicted likely pathogenic (of 1,580 scored), across 112 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D151	8	0.985	0.997
D193	8	0.984	0.994
F174	8	0.980	0.999
F89	8	0.951	0.997
F77	8	0.923	0.984
D137	8	0.880	0.976
S138	8	0.874	0.986
C136	7	0.998	1.000
C201	7	0.998	0.999
C189	7	0.997	0.999
C231	7	0.997	0.999
C229	7	0.996	0.998
C179	7	0.994	0.999
W197	7	0.994	1.000
F207	7	0.994	0.999
W220	7	0.992	0.999
W142	7	0.988	0.999
F222	7	0.986	0.994
F175	7	0.983	0.990
E176	7	0.962	0.997

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Renal Clear Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	6e-06
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000457

Disease associations

OMIM: gene MIM:162030 | disease phenotypes: MIM:608654

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
hereditary sensory and autonomic neuropathy	Strong	Autosomal recessive
hereditary sensory and autonomic neuropathy type 5	Strong	Autosomal recessive	4

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
hereditary sensory and autonomic neuropathy	Strong	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Familial dysautonomia	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Pain syndromes	green

Mondo (3): hereditary sensory and autonomic neuropathy type 5 (MONDO:0012092), peripheral neuropathy (MONDO:0005244), hereditary sensory and autonomic neuropathy (MONDO:0015364)

Orphanet (1): Hereditary sensory and autonomic neuropathy type 5 (Orphanet:64752)

HPO phenotypes

30 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000164	Abnormality of the dentition
HP:0000168	Abnormal gingiva morphology
HP:0000272	Malar flattening
HP:0000490	Deeply set eye
HP:0000970	Anhidrosis
HP:0001058	Poor wound healing
HP:0001256	Mild intellectual disability
HP:0001954	Recurrent fever
HP:0002014	Diarrhea
HP:0002019	Constipation
HP:0002378	Hand tremor
HP:0002495	Impaired vibratory sensation
HP:0002661	Painless fractures due to injury
HP:0002754	Osteomyelitis
HP:0002757	Recurrent fractures
HP:0002758	Osteoarthritis
HP:0003040	Arthropathy
HP:0003095	Septic arthritis
HP:0003419	Low back pain
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0006121	Acral ulceration
HP:0007021	Pain insensitivity
HP:0007249	Decreased number of small peripheral myelinated nerve fibers
HP:0007328	Impaired pain sensation
HP:0009830	Peripheral neuropathy
HP:0010829	Impaired temperature sensation
HP:0011463	Childhood onset

GWAS associations

15 associations:

Study	Trait	p-value
GCST003720_30	Migraine	4e-24
GCST006656_1	Dysmenorrheic pain severity	1e-19
GCST003927_1	Dysmenorrheic pain	4e-14
GCST003986_9	Migraine	2e-13
GCST006637_5	Pain medicine use during menstruation	2e-13
GCST006636_4	Menstruation quality of life impact (dysmenorrhea)	8e-12
GCST007094_46	Diastolic blood pressure	1e-11
GCST010866_114	Coronary artery disease	9e-11
GCST90002403_530	Red blood cell count	2e-10
GCST003721_1	Migraine without aura	7e-9
GCST003720_6	Migraine	9e-9
GCST007099_121	Systolic blood pressure	1e-7
GCST007201_344	Schizophrenia	4e-7
GCST004227_3	Obstetric antiphospholipid syndrome	4e-6
GCST001928_1	Pediatric non-alcoholic fatty liver disease activity score	7e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0007889	dysmenorrheic pain measurement
EFO:0007010	drug use measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004305	erythrocyte count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D009477	Hereditary Sensory and Autonomic Neuropathies	C10.500.250; C10.574.500.493; C10.668.829.800.175; C16.131.666.310; C16.320.400.415

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1649058 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the NGF protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

5 curated-mechanism drugs:

Drug	Modality	Max phase
FASINUMAB	Antibody	3
FULRANUMAB	Antibody	3
TANEZUMAB	Antibody	3
MEDI-578	Unknown	1
PG-110	Unknown	1

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs2239622	Dosage	3	methadone	Heroin Dependence;Opioid-Related Disorders

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2239622	NGF	3	0.75	1	methadone

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2239622	methadone	Dosage	Genotype AA is associated with decreased dose of methadone in people with Opioid-Related Disorders as compared to genotypes AG + GG.	PMID:21358750

Binding affinities (BindingDB)

1 measured of 3 human assays (3 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL1397270	IC50	1000 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.00	IC50	1000	nM	CHEMBL1397270

PubChem BioAssay actives

1 with measured affinity, of 8 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
7,10-dimethyl-2,4-dioxobenzo[g]pteridine-8-carbaldehyde	700919: Inhibition of NGF binding to p75NTR	ic50	1.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Copper	affects binding, increases expression	2
Nicotine	increases expression, increases secretion	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	decreases reaction, increases phosphorylation	1
mangiferin	increases secretion	1
sulforaphane	increases activity, increases expression, decreases phosphorylation, decreases reaction	1
sodium arsenite	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
manganese chloride	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
beclomethasone 17-monopropionate	decreases reaction, increases secretion, decreases secretion	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
methanandamide	decreases reaction, increases expression	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
U 0126	decreases reaction, increases expression	1
pyrazolanthrone	decreases reaction, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects expression	1
jinfukang	increases reaction, decreases expression	1
NSC 689534	affects binding, increases expression	1
Calcimycin	decreases expression, affects cotreatment, decreases reaction, increases expression	1
Temozolomide	decreases expression	1
Edaravone	increases expression, decreases reaction	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Berberine	decreases expression, decreases reaction, increases expression	1
Cadmium	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1648454	Binding	Induction of neurotrophic factor mRNA expression in human 1321N1 cells at 100 uM by RT-PCR analysis relative to beta-actin mRNA expression	Lyconadins D and E, and complanadine E, new Lycopodium alkaloids from Lycopodium complanatum. — *Bioorg Med Chem*

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 2 spontaneously immortalized cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4P7	SEES3-1V human NGF, clone1	Embryonic stem cell	Male
CVCL_A4P8	SEES3-1V human NGF, clone2	Embryonic stem cell	Male
CVCL_A4P9	SEES3-1V human NGF, clone3	Embryonic stem cell	Male
CVCL_DF65	NGC0211	Spontaneously immortalized cell line	Male
CVCL_DF66	NGC-0295	Spontaneously immortalized cell line	Male
CVCL_UG27	UKWNLi002-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 303 trials:

NCT	Phase	Status	Title
NCT00380965	Phase 4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	Phase 4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	Phase 4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	Phase 4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	Phase 4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	Phase 4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	Phase 4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	Phase 4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	Phase 4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	Phase 4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	Phase 4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT00058071	Phase 3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	Phase 3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	Phase 3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	Phase 3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	Phase 3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	Phase 3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	Phase 3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	Phase 3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	Phase 3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	Phase 3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	Phase 3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	Phase 3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	Phase 3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	Phase 3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	Phase 3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	Phase 3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	Phase 3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	Phase 3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	Phase 3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	Phase 3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	Phase 3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	Phase 3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	Phase 3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	Phase 3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	Phase 3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	Phase 3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	Phase 3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	Phase 3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT07287592	Phase 3	NOT_YET_RECRUITING	Glutamine for the Prophylaxis of Vincristine-induced Neuropathy in Children and Adolescents With Cancer.
NCT02624310	Phase 2	WITHDRAWN	A Study of Norepinephrine in Patients With Congenital Insensitivity to Pain and Anhidrosis
NCT00006072	Phase 2	UNKNOWN	A Study of Rituxan in the Treatment of Polyneuropathies Associated With Serum IgM Autoantibodies
NCT00365768	Phase 2	COMPLETED	Glutamine in Treating Neuropathy Caused by Vincristine in Young Patients With Lymphoma, Leukemia, or Solid Tumors
NCT00475904	Phase 2	COMPLETED	A Comparison of EpiCept™ NP-1 Topical Cream vs. Oral Gabapentin in Postherpetic Neuralgia (PHN)
NCT00528593	Phase 2	WITHDRAWN	Epoetin Alfa for HIV-Associated Neuropathy Trial
NCT00603265	Phase 2	COMPLETED	Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
NCT00665652	Phase 2	TERMINATED	Study of Lenalidomide as a Treatment for Neuropathy Associated With Monoclonal Gammopathy of Undetermined Significance
NCT00863057	Phase 2	TERMINATED	Combination Pain Therapy in HIV Neuropathy
NCT00891618	Phase 2	COMPLETED	Acupuncture for Chemo-Induced Peripheral Neuropathy
NCT00952848	Phase 2	COMPLETED	Electrical Stimulation Therapy Using the MC5-A Scrambler in Reducing Peripheral Neuropathy Caused by Chemotherapy
NCT01135251	Phase 2	COMPLETED	Safety and Preliminary Evidence of Efficacy of Escalating Doses of Dimiracetam in AIDS Patients With Painful Neuropathy
NCT01278004	Phase 2	COMPLETED	Chemotherapy Induced Painful Peripheral Neuropathy Ethosuximide (The CIN-E Study)
NCT01290224	Phase 2	COMPLETED	MC5-A Scrambler Therapy in Reducing Peripheral Neuropathy Caused by Chemotherapy
NCT01451853	Phase 2	WITHDRAWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01480297	Phase 2	COMPLETED	Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy
NCT01506453	Phase 2	COMPLETED	Therapeutic Interventions For Pain Induced By Vincristine Treatment For Childhood Acute Lymphoblastic Leukemia (ALL)
NCT01523574	Phase 2	COMPLETED	Vitamin E for Oxaliplatin-induced Peripheral Neuropathy Prophylaxis
NCT01637077	Phase 2	COMPLETED	Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel
NCT01655823	Phase 2	TERMINATED	The Purpose of This Study is to Determine if Tetrodotoxin (TTX) is Effective in the Treatment of Pain Resulting From Chemotherapy Treatment
NCT01774058	Phase 2	UNKNOWN	The Arterial Measurement of the Blood Flow Volume After Iloprost Stimulation

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NGF across ~30M SureChEMBL compounds — explore on Sugi Predict.