NGFR

Summary

NGFR (nerve growth factor receptor, HGNC:7809) is a protein-coding gene on chromosome 17q21.33, encoding Tumor necrosis factor receptor superfamily member 16 (P08138). Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4.

Nerve growth factor receptor contains an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155-amino acid cytoplasmic domain. The cysteine-rich region contains the nerve growth factor binding domain.

Source: NCBI Gene 4804 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 80 total
• Druggable target: yes
• MANE Select transcript: NM_002507

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7809
Approved symbol	NGFR
Name	nerve growth factor receptor
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	TNFRSF16, CD271, p75NTR
Ensembl gene	ENSG00000064300
Ensembl biotype	protein_coding
OMIM	162010
Entrez	4804

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000172229, ENST00000504201, ENST00000509200

RefSeq mRNA: 1 — MANE Select: NM_002507 NM_002507

CCDS: CCDS11549

Canonical transcript exons

ENST00000172229 — 6 exons

Exon	Start	End
ENSE00000736276	49510412	49510664
ENSE00000736277	49511892	49512052
ENSE00000819771	49495293	49495483
ENSE00000819772	49512708	49515008
ENSE00003598821	49502063	49502204
ENSE00003634542	49506299	49506658

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 97.58.

FANTOM5 (CAGE): breadth broad, TPM avg 9.3437 / max 434.9079, expressed in 844 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161533	8.7039	823
161534	0.6000	154
161535	0.0398	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nerve	UBERON:0001021	97.58	gold quality
tibial nerve	UBERON:0001323	97.58	gold quality
dorsal root ganglion	UBERON:0000044	95.96	gold quality
apex of heart	UBERON:0002098	93.63	gold quality
sural nerve	UBERON:0015488	93.30	gold quality
right atrium auricular region	UBERON:0006631	90.54	gold quality
right lobe of thyroid gland	UBERON:0001119	90.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.98	silver quality
trigeminal ganglion	UBERON:0001675	89.67	gold quality
cardiac atrium	UBERON:0002081	89.07	gold quality
omental fat pad	UBERON:0010414	87.88	gold quality
left uterine tube	UBERON:0001303	87.83	gold quality
peritoneum	UBERON:0002358	87.81	gold quality
left lobe of thyroid gland	UBERON:0001120	85.69	gold quality
left coronary artery	UBERON:0001626	85.61	gold quality
olfactory bulb	UBERON:0002264	85.56	silver quality
right lobe of liver	UBERON:0001114	85.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.92	gold quality
left adrenal gland	UBERON:0001234	84.89	gold quality
right adrenal gland cortex	UBERON:0035827	84.80	gold quality
right adrenal gland	UBERON:0001233	84.57	gold quality
left adrenal gland cortex	UBERON:0035825	84.37	gold quality
coronary artery	UBERON:0001621	84.29	gold quality
minor salivary gland	UBERON:0001830	84.25	gold quality
right coronary artery	UBERON:0001625	84.14	gold quality
adrenal gland	UBERON:0002369	83.47	gold quality
adrenal cortex	UBERON:0001235	83.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.35	gold quality
thyroid gland	UBERON:0002046	83.34	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	24.12
E-HCAD-11	yes	23.37
E-GEOD-135922	yes	22.10
E-MTAB-8142	yes	12.03
E-ANND-3	yes	3.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CEBPB, CLOCK, CUX1, EGR1, EGR3, EZH2, HAND1, HAND2, IGF1, MEF2A, MITF, MYCN, MYOD1, NFKB, SP1, SSRP1, TCF12, ZBTB17

miRNA regulators (miRDB)

113 targeting NGFR, 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-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
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-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3934-3P	99.76	65.51	1351

Literature-anchored findings (GeneRIF, showing 40)

• Nerve growth factor regulates dopamine D(2) receptor expression in prolactinoma cell lines via p75(NGFR)-mediated activation of nuclear factor-kappaB (PMID:11818506)
• results indicate that neurons expressing p75(NTR), mostly if expressing also proinflammatory cytokine receptors, might be preferential targets of the cytotoxic action of Abeta in Alzheimer’s disease (p75 neurotrophin receptor) (PMID:11927634)
• Rabies virus glycoprotein (RVG) is a trimeric ligand for the N-terminal cysteine-rich domain of this protein (PMID:12163480)
• P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG (myelin-associated glycoprotein) and OMgp (PMID:12422217)
• p75(NTR) may be involved in the formation of tangles in the Alzheimer process. (PMID:12460612)
• tumor necrosis factor receptor-associated death domain protein (TRADD) interacts with p75(NTR) upon nerve growth factor (NGF) stimulation in breast cancer cells (PMID:12604596)
• p75(NTR) tumor suppressor induces caspase-mediated apoptosis in bladder tumor cells (PMID:12672029)
• Data describe the identification of a variant of the beta catalytic subunit of cyclic AMP-dependent protein kinase (PKACbeta) as a p75 neurotrophin receptor(NTR)-interacting protein, which phosphorylates p75(NTR) at Ser304. (PMID:12682012)
• p75 neurotrophin receptor (p75NTR) expression is induced by osmotic swelling via nitric oxide (PMID:12821676)
• p75(NTR) has a role in differentiation of human esophageal keratinocyte stem cells (PMID:12821936)
• gamma-secretase-mediated p75NTR proteolysis plays a role in the formation/disassembly of the p75-TrkA receptor complex by regulating the availability of the p75 TM domain that is required for this interaction (PMID:12913006)
• Using yeast two-hybrid systems, RanBPM was identified as a binding partner of p75(NTR). (PMID:12963025)
• The p75(NTR)-mediated trophic support profoundly affects competitive melanoma-cell survival when the tumor cell microenvironment becomes growth limiting. (PMID:14689592)
• p75NTR activation has diverse effects on neuroblastomas. (PMID:15015775)
• p75-NGFR expression is observed in fetuses from 15 weeks of gestation in the borderline between pars intermedia and the neurohypophysis. (PMID:15165637)
• Data show that sustained activation of p38(MAPK) is essential for the death cascade following exposure of Ewing’s sarcoma tumor cells to bFGF and provide evidence that activation of p38(MAPK) results in an up-regulation of the death receptor p75(NTR). (PMID:15310753)
• c-Cbl-dependent ubiquitination of p75NTR involved in the regulation of p75NTR signalling. (PMID:15337528)
• 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)
• pro-NGF purified from AD human brains can induce apoptosis in neuronal cell cultures through its interaction with the p75NTR receptor (PMID:15681836)
• In rat, p75 neurotrophin receptor cleavage by alpha-secretase and gamma-secretase requires specific receptor domains. (PMID:15701642)
• This review focuses on p75NTR as a facilitator of Trk receptor tyrosine kinase-mediated neuronal survival and as a regulator of neuronal cell death–opposing roles dictated by distinct partnering molecules. (PMID:15721744)
• signaling pathway in which Abeta peptide binds to p75NTR and activates p38 and JNK in a DD-dependent manner, followed by NF-kappaB translocation and p53 activation cause neuron death (PMID:15784962)
• trimeric oligomerization state of Rabies virus G protein is required for binding with p75NTR (PMID:16099913)
• p75(NTR) and Fas receptors could share common signalling pathways. (PMID:16215672)
• p75(NTR) retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. (PMID:16460673)
• Loss of p75 neurotrophin receptor expression accompanies malignant progression to human and murine retinoblastoma (PMID:16555252)
• In dermis of atopic dermatitis (AD), the intensity of p75 NGFr-IR nerves was stronger in areas of increased numbers of NGF-IR cells. Nerve growth factor and its receptors may contribute to the neurohyperplasia of AD. (PMID:16586073)
• Elevated p75NGFR expression is associated with a favorable prognosis in human pancreatic cancer. (PMID:16704535)
• Expressions of p75(NTR) and heparanase-1 correlated with each other in medulloblastoma. (PMID:16826429)
• This review focuses on the interactions between Abeta and p75NTR in the context of the broader p75NTR signalling field, and offers alternative explanations for how p75NTR might contribute to the etiology of Alzheimer’s disease. (PMID:16893414)
• The p75NTR is necessary for survival and maintenance of esophageal squamous cell carcinoma (ESCC), providing us with a potential target for novel therapies. (PMID:16951226)
• p75 is a potential marker of oral keratinocyte stem/progenitor cells and that some neurotrophin/p75 signaling affects cell growth and survival. (PMID:17110619)
• We propose that TrkA and p75 likely communicate through convergence of downstream signaling pathways and/or shared adaptor molecules, rather than through direct extracellular interactions. (PMID:17196528)
• Conserved elements were found in the 25 kb upstream sequences of the human p75NTR gene. Only 1 of these, a proximal region rich in Sp1 sites, responds to changes in hypo-osmolarity. (PMID:17287525)
• The novel finding that a mutation may increase processing of p75NTR may have implications for the pathogenic outcome in Alzheimer’s disease (PMID:17349981)
• results do not support an association of the p75(NTR) S205L polymorphism with risk for childhood-onset mood disorder(COMD)or suicide attempt in COMD (PMID:17357149)
• p75 neurotrophin receptor forms may have a role in type 2 diabetic patients (PMID:17492429)
• p75NTR had the function of inhibiting the invasive and metastatic abilities of gastric cancer cells, which was mediated, at least partially, by down-regulation of uPA and MMP9 proteins and up-regulation of TIMP1 protein. (PMID:17510309)
• trkA(NGFR) and p75(NTR) have roles with nerve growth factor in the healing process as a result of injury [review] (PMID:17531524)
• p75NTR downstream signalling is altered by PS2 mutation or gamma-secretase inhibition in SHSY-5Y cel (PMID:17582777)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ngfra	ENSDARG00000088708
danio_rerio	ngfrb	ENSDARG00000089223
mus_musculus	Ngfr	ENSMUSG00000000120
rattus_norvegicus	Ngfr	ENSRNOG00000005392

Paralogs (21): FAS (ENSG00000026103), TNFRSF1B (ENSG00000028137), TNFRSF9 (ENSG00000049249), RELT (ENSG00000054967), TNFRSF1A (ENSG00000067182), CD40 (ENSG00000101017), TNFRSF10A (ENSG00000104689), LTBR (ENSG00000111321), TNFRSF10B (ENSG00000120889), TNFRSF8 (ENSG00000120949), CD27 (ENSG00000139193), TNFRSF11A (ENSG00000141655), TNFRSF21 (ENSG00000146072), TNFRSF14 (ENSG00000157873), TNFRSF11B (ENSG00000164761), TNFRSF10D (ENSG00000173530), TNFRSF10C (ENSG00000173535), TNFRSF4 (ENSG00000186827), TNFRSF18 (ENSG00000186891), TNFRSF25 (ENSG00000215788), TNFRSF6B (ENSG00000243509)

Protein

Protein identifiers

Tumor necrosis factor receptor superfamily member 16 — P08138 (reviewed: P08138)

Alternative names: Gp80-LNGFR, Low affinity neurotrophin receptor p75NTR, Low-affinity nerve growth factor receptor, Low-affinity nerve growth factor receptor p75NGFR, Low-affinity nerve growth factor receptor p75NGR, p75 ICD

All UniProt accessions (1): P08138

UniProt curated annotations — full annotation on UniProt →

Function. Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4. Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF, BDNF and NTF3 with high affinity, and has much lower affinity for mature NGF and BDNF. Plays an important role in differentiation and survival of specific neuronal populations during development. Can mediate cell survival as well as cell death of neural cells. Plays a role in the inactivation of RHOA. Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake. Necessary for the circadian oscillation of the clock genes BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCmgetaN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver. Together with BFAR negatively regulates NF-kappa-B and JNK-related signaling pathways.

Subunit / interactions. Homodimer; disulfide-linked. Heterodimer with SORCS2. The extracellular domains of the heterodimer bind NGF. The cytoplasmic region of the heterodimer binds TRIO. NGF binding mediates dissociation of TRIO from the receptor complex. Interacts with RTN4R. Interacts with TRAF2, TRAF4, TRAF6, PTPN13 and RANBP9. Interacts through TRAF6 with SQSTM1 which bridges NGFR to NTRK1. Interacts with BEX1. Interacts with BEX3. Interacts with KIDINS220 and NTRK1. Can form a ternary complex with NTRK1 and KIDINS220 and this complex is affected by the expression levels of KIDINS220. An increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1. Interacts with NTRK2; may regulate the ligand specificity of the NTRK2 receptor. Interacts (via death domain) with RAB31. Interacts with LINGO1. Interacts with NRADD. Interacts with MAGED1; the interaction antagonizes the association NGFR:NTRK1. Interacts (via death domain) with ARHGDIA and RIPK2. Interacts with BFAR.

Subcellular location. Cell membrane. Cytoplasm. Perikaryon. Cell projection. Growth cone. Dendritic spine.

Post-translational modifications. N- and O-glycosylated. O-linked glycans consist of Gal(1-3)GalNAc core elongated by 1 or 2 NeuNAc. Phosphorylated on serine residues.

Domain organisation. The death domain mediates interaction with RANBP9. It also mediates interaction with ARHGDIA and RIPK2. The extracellular domain is responsible for interaction with NTRK1.

Isoforms (2)

UniProt ID	Names	Canonical?
P08138-1	1	yes
P08138-2	2

RefSeq proteins (1): NP_002498* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000488	Death_dom	Domain
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR022325	TNFR_16	Family
IPR034046	TNFRSF16_N	Domain
IPR041448	TNFR16_TM	Domain
IPR052302	Neurotrophin_rcpt-DD	Family

Pfam: PF00020, PF00531, PF18422

UniProt features (53 total): disulfide bond 12, helix 8, strand 6, turn 4, repeat 4, region of interest 3, compositionally biased region 3, mutagenesis site 3, topological domain 2, signal peptide 1, chain 1, modified residue 1, glycosylation site 1, transmembrane region 1, splice variant 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3EWV	X-RAY DIFFRACTION	2.6
2N80	SOLUTION NMR
2N83	SOLUTION NMR
2N97	SOLUTION NMR
5ZGG	SOLUTION NMR
7CSQ	SOLUTION NMR
8X8T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08138-F1	76.44	0.45

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 (1): 311

Disulfide bonds (12): 32–43, 44–57, 47–64, 67–83, 86–99, 89–107, 109–122, 125–138, 128–146, 149–164, 167–180, 170–188

Glycosylation sites (1): 60

Mutagenesis-validated functional residues (3):

Position	Phenotype
343	decreased interaction with arhgdia.
412	decreased interaction with arhgdia.
420	decreased interaction with arhgdia.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-193634	Axonal growth inhibition (RHOA activation)
R-HSA-193648	NRAGE signals death through JNK
R-HSA-193670	p75NTR negatively regulates cell cycle via SC1
R-HSA-193681	Ceramide signalling
R-HSA-193692	Regulated proteolysis of p75NTR
R-HSA-205017	NFG and proNGF binds to p75NTR
R-HSA-205025	NADE modulates death signalling
R-HSA-205043	NRIF signals cell death from the nucleus
R-HSA-209543	p75NTR recruits signalling complexes
R-HSA-209560	NF-kB is activated and signals survival
R-HSA-209563	Axonal growth stimulation

MSigDB gene sets: 364 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, CHIBA_RESPONSE_TO_TSA_UP, GOBP_EPIDERMIS_MORPHOGENESIS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, PEREZ_TP63_TARGETS, MODULE_64, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, AREB6_03, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION

GO Biological Process (39): intracellular glucose homeostasis (GO:0001678), intracellular protein transport (GO:0006886), Rho protein signal transduction (GO:0007266), axon guidance (GO:0007411), central nervous system development (GO:0007417), fibroblast growth factor receptor signaling pathway (GO:0008543), detection of temperature stimulus (GO:0016048), nerve development (GO:0021675), negative regulation of cell migration (GO:0030336), hair follicle morphogenesis (GO:0031069), circadian regulation of gene expression (GO:0032922), dorsal aorta development (GO:0035907), negative regulation of fibroblast growth factor receptor signaling pathway (GO:0040037), odontogenesis of dentin-containing tooth (GO:0042475), positive regulation of odontogenesis of dentin-containing tooth (GO:0042488), glucose homeostasis (GO:0042593), fibroblast proliferation (GO:0048144), positive regulation of fibroblast proliferation (GO:0048146), neuron apoptotic process (GO:0051402), negative regulation of hair follicle development (GO:0051799), extrinsic apoptotic signaling pathway (GO:0097191), presynaptic modulation of chemical synaptic transmission (GO:0099171), positive regulation of protein localization to nucleus (GO:1900182), positive regulation of miRNA transcription (GO:1902895), negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis (GO:1903588), cellular response to amyloid-beta (GO:1904646), positive regulation of endothelial cell apoptotic process (GO:2000353), positive regulation of apoptotic signaling pathway (GO:2001235), hair follicle development (GO:0001942), apoptotic process (GO:0006915), signal transduction (GO:0007165), nervous system development (GO:0007399), circadian rhythm (GO:0007623), regulation of gene expression (GO:0010468), cell differentiation (GO:0030154), regulation of cell population proliferation (GO:0042127), positive regulation of apoptotic process (GO:0043065), skin development (GO:0043588), rhythmic process (GO:0048511)

GO Molecular Function (11): amyloid-beta binding (GO:0001540), transmembrane signaling receptor activity (GO:0004888), death receptor activity (GO:0005035), calmodulin binding (GO:0005516), coreceptor activity (GO:0015026), small GTPase binding (GO:0031267), ubiquitin protein ligase binding (GO:0031625), signaling receptor activity (GO:0038023), neurotrophin binding (GO:0043121), nerve growth factor binding (GO:0048406), protein binding (GO:0005515)

GO Cellular Component (18): extracellular region (GO:0005576), nucleoplasm (GO:0005654), endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), cell surface (GO:0009986), postsynaptic density (GO:0014069), membrane (GO:0016020), growth cone (GO:0030426), neuromuscular junction (GO:0031594), dendritic spine (GO:0043197), perikaryon (GO:0043204), presynapse (GO:0098793), cytoplasm (GO:0005737), cell projection (GO:0042995), organelle (GO:0043226), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
p75 NTR receptor-mediated signalling	4
Cell death signalling via NRAGE, NRIF and NADE	3
p75NTR regulates axonogenesis	2
p75NTR signals via NF-kB	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	10
nervous system development	2
hair follicle development	2
signaling receptor activity	2
synapse	2
glucose homeostasis	1
intracellular chemical homeostasis	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
small GTPase-mediated signal transduction	1
axonogenesis	1
neuron projection guidance	1
system development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
response to temperature stimulus	1
detection of external stimulus	1
detection of abiotic stimulus	1
anatomical structure development	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
anatomical structure morphogenesis	1
hair cycle process	1
epidermis morphogenesis	1
circadian rhythm	1
regulation of gene expression	1
aorta development	1
fibroblast growth factor receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of fibroblast growth factor receptor signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
odontogenesis	1
odontogenesis of dentin-containing tooth	1
positive regulation of odontogenesis	1
regulation of odontogenesis of dentin-containing tooth	1
carbohydrate homeostasis	1
cell population proliferation	1
positive regulation of cell population proliferation	1

Protein interactions and networks

STRING

2392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NGFR	NGF	P01138	999
NGFR	NTRK1	P04629	999
NGFR	NTF3	P20783	998
NGFR	BDNF	P23560	998
NGFR	NTF4	P34130	998
NGFR	SORT1	Q99523	997
NGFR	RTN4R	Q9BZR6	996
NGFR	LINGO1	Q96FE5	995
NGFR	NTRK2	Q16620	985
NGFR	RTN4	Q9NQC3	957
NGFR	NTRK3	Q16288	956
NGFR	MAGED1	Q9Y5V3	942
NGFR	SORCS2	Q96PQ0	894
NGFR	BEX3	Q00994	888
NGFR	OMG	P23515	883

IntAct

61 interactions, top by confidence:

A	B	Type	Score
CD80	NGFR	psi-mi:“MI:0915”(physical association)	0.800
CD80	NGFR	psi-mi:“MI:0407”(direct interaction)	0.800
NGFR	CD80	psi-mi:“MI:0915”(physical association)	0.800
CD80	NGFR	psi-mi:“MI:0403”(colocalization)	0.800
SORT1	NGF	psi-mi:“MI:0915”(physical association)	0.680
NGFR	Ndn	psi-mi:“MI:0915”(physical association)	0.600
Nsmce3	NGFR	psi-mi:“MI:0915”(physical association)	0.600
NGFR	Ndn	psi-mi:“MI:0407”(direct interaction)	0.600
Nsmce3	NGFR	psi-mi:“MI:0407”(direct interaction)	0.600
NGFR	Nsmce3	psi-mi:“MI:0915”(physical association)	0.600
NGFR	LINGO1	psi-mi:“MI:0915”(physical association)	0.590
LINGO1	NGFR	psi-mi:“MI:0915”(physical association)	0.590
SALL2	NGFR	psi-mi:“MI:0915”(physical association)	0.580
NGFR	SALL2	psi-mi:“MI:0915”(physical association)	0.580
APP	NGFR	psi-mi:“MI:0407”(direct interaction)	0.560
STUB1	NGFR	psi-mi:“MI:0915”(physical association)	0.560
SPRED1	NGFR	psi-mi:“MI:0915”(physical association)	0.560
NGFR	TNFRSF21	psi-mi:“MI:0915”(physical association)	0.540
NGFR	TNFRSF21	psi-mi:“MI:0407”(direct interaction)	0.540

BioGRID (123): PRKACB (Two-hybrid), NGFR (Affinity Capture-Western), MDM2 (Affinity Capture-Western), NGFR (Affinity Capture-Western), TP53 (Affinity Capture-Western), NGFR (Reconstituted Complex), NGFR (Affinity Capture-Western), NGFR (Reconstituted Complex), NGFR (Reconstituted Complex), NTRK2 (Affinity Capture-Western), NGFR (Affinity Capture-Western), NGFR (Affinity Capture-Western), NGFR (Affinity Capture-Western), NDNL2 (Two-hybrid), NDN (Reconstituted Complex)

ESM2 similar proteins: A0JNA2, A2RRU4, A6QM06, C0HL12, D3ZTD8, O14514, O54693, O60241, O60242, O75077, O75462, P08138, P97260, Q0GA42, Q13591, Q29RN8, Q3TMX7, Q3UHD1, Q4V7F2, Q4V9Z5, Q53EL9, Q5R7Y0, Q5VXM1, Q62217, Q6GQT6, Q6UXD5, Q6ZRP7, Q7TSK2, Q7TSQ1, Q7TT36, Q80ZF8, Q8BQC3, Q8BQH6, Q8CGM1, Q8IVU1, Q8IWK6, Q91XD7, Q924S4, Q92838, Q96MU8

Diamond homologs: A5D7R1, O00300, O08712, O08727, O35305, O73559, O95407, P07174, P08138, P0DTN0, P15725, P20333, P20334, P25119, P25942, P27512, P36941, P43489, P47741, P50284, P68636, P68637, Q07011, Q28203, Q3LRP1, Q3ZTK5, Q7YRL5, Q8SQ34, Q9Y6Q6, Q9Z0W1, P18519, P25943, Q80WM9, Q8CJ26, Q8K5A9, P22934, Q9ER62, D3ZF92, O75509, P0DSV7

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
NGF	up-regulates	NGFR	binding
NGFR	up-regulates	Apoptosis
NGFR	up-regulates	MAPK10
NGFR	up-regulates	Cell_death
PRKACB	up-regulates	NGFR	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1152 predictions. Top by Δscore:

Variant	Effect	Δscore
17:49495480:GGGG:G	donor_gain	1.0000
17:49495481:GGGG:G	donor_gain	1.0000
17:49502205:G:GG	donor_gain	1.0000
17:49503937:G:GT	donor_gain	1.0000
17:49503937:G:T	donor_gain	1.0000
17:49506655:GAGG:G	donor_gain	1.0000
17:49506657:GG:G	donor_gain	1.0000
17:49506658:GG:G	donor_gain	1.0000
17:49506659:G:GA	donor_loss	1.0000
17:49506659:G:GG	donor_gain	1.0000
17:49506660:T:A	donor_loss	1.0000
17:49510661:AGAGG:A	donor_loss	1.0000
17:49510662:GAG:G	donor_gain	1.0000
17:49510662:GAGGT:G	donor_loss	1.0000
17:49510664:GGTA:G	donor_loss	1.0000
17:49510665:G:GA	donor_loss	1.0000
17:49510666:T:G	donor_loss	1.0000
17:49511883:T:TA	acceptor_gain	1.0000
17:49511884:G:A	acceptor_gain	1.0000
17:49511888:CCAG:C	acceptor_loss	1.0000
17:49511890:A:AG	acceptor_gain	1.0000
17:49511891:G:GG	acceptor_gain	1.0000
17:49511891:GGT:G	acceptor_gain	1.0000
17:49512049:CAGGG:C	donor_loss	1.0000
17:49512050:AGGGT:A	donor_loss	1.0000
17:49512051:GG:G	donor_gain	1.0000
17:49512052:GG:G	donor_gain	1.0000
17:49512052:GGT:G	donor_loss	1.0000
17:49512053:GTGAG:G	donor_loss	1.0000
17:49512054:T:G	donor_loss	1.0000

AlphaMissense

2769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:49506473:G:A	C128Y	0.999
17:49506481:G:T	G131C	0.999
17:49506535:T:A	C149S	0.999
17:49506535:T:C	C149R	0.999
17:49506536:G:C	C149S	0.999
17:49506550:T:G	Y154D	0.999
17:49506553:T:C	S155P	0.999
17:49506580:T:A	C164S	0.999
17:49506580:T:C	C164R	0.999
17:49506581:G:A	C164Y	0.999
17:49506581:G:C	C164S	0.999
17:49506582:C:G	C164W	0.999
17:49506652:T:A	C188S	0.999
17:49506653:G:C	C188S	0.999
17:49506307:T:C	F73L	0.998
17:49506309:C:A	F73L	0.998
17:49506309:C:G	F73L	0.998
17:49506346:T:A	C86S	0.998
17:49506347:G:A	C86Y	0.998
17:49506347:G:C	C86S	0.998
17:49506348:C:G	C86W	0.998
17:49506385:T:A	C99S	0.998
17:49506385:T:C	C99R	0.998
17:49506386:G:A	C99Y	0.998
17:49506386:G:C	C99S	0.998
17:49506387:C:G	C99W	0.998
17:49506409:T:A	C107S	0.998
17:49506410:G:C	C107S	0.998
17:49506415:T:A	C109S	0.998
17:49506416:G:C	C109S	0.998

dbSNP variants (sampled 300 via entrez): RS1000066714 (17:49504900 T>C), RS1000072361 (17:49502355 G>A), RS1000089383 (17:49495259 C>T), RS1000155098 (17:49496560 C>A), RS1000224647 (17:49501773 T>C), RS1000378047 (17:49515097 G>A), RS1000461663 (17:49495382 G>A,C), RS1000471622 (17:49513581 C>T), RS1000527951 (17:49500489 A>T), RS1000688235 (17:49513775 A>G), RS1000721948 (17:49514053 C>T), RS1000840010 (17:49512344 G>A), RS1001228500 (17:49495136 C>A), RS1001236412 (17:49514403 C>T), RS1001428329 (17:49502599 G>A)

Disease associations

OMIM: gene MIM:162010 | 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
GCST001535_2	Immune reponse to smallpox (secreted IL-2)	2.000000e-08
GCST001942_17	Prostate cancer	2.000000e-09
GCST004493_9	Lower body strength	9.000000e-06
GCST90002397_576	Mean spheric corpuscular volume	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0007999	lower body strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4762 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2072446	NGFR		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Tumour necrosis factor (TNF) receptor family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
NGF		6.0	pIC50

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.70	IC50	200	nM	CHEMBL137953
5.89	IC50	1300	nM	CHEMBL136617
5.64	IC50	2300	nM	CHEMBL342150
5.51	IC50	3100	nM	CHEMBL139216
5.43	IC50	3720	nM	CHEMBL440470

PubChem BioAssay actives

5 with measured affinity, of 32 total; 5 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-benzamido-4-methyl-9-oxopyrazolo[5,1-b]quinazoline-2-carboxylic acid	147189: Inhibition of [125I]- NGF binding to extracellular domain of p75 receptor	ic50	0.2000	uM
methyl 2-methyl-7-oxo-5-(tetrazol-1-ylcarbamoyl)-4H-thieno[3,2-b]pyridine-3-carboxylate	147189: Inhibition of [125I]- NGF binding to extracellular domain of p75 receptor	ic50	1.3000	uM
3-methoxycarbonyl-2-methyl-7-oxo-4H-thieno[3,2-b]pyridine-5-carboxylic acid	147189: Inhibition of [125I]- NGF binding to extracellular domain of p75 receptor	ic50	2.3000	uM
6-amino-4-oxo-1H-quinoline-2-carboxylic acid	147189: Inhibition of [125I]- NGF binding to extracellular domain of p75 receptor	ic50	3.1000	uM
2-(2-hydroxyethylamino)-5-nitrobenzo[de]isoquinoline-1,3-dione	147188: Competitive binding against Nerve growth factor to p75-NGF receptor in PC12 cells	ic50	3.7200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Estradiol	decreases expression, increases expression, affects cotreatment	4
Flurbiprofen	increases reaction, affects binding, increases stability, decreases reaction, increases expression	4
Ibuprofen	increases expression, increases reaction, affects binding, increases stability, decreases reaction	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases expression	3
Aflatoxin B1	increases expression	3
bisphenol A	affects expression, affects cotreatment, increases expression	2
Vorinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases expression, affects cotreatment, increases abundance, increases oxidation	2
Doxorubicin	decreases expression, increases expression	2
Ozone	increases oxidation, increases abundance, increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	affects cotreatment, increases expression, affects reaction, increases activity	2
Cadmium Chloride	affects reaction, increases cleavage, decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
lly-283	decreases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
dimethylselenide	increases expression, increases oxidation	1
sulforaphane	increases expression, decreases reaction	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3861733	Binding	Inhibition of mouse NGF binding to p75 (unknown origin) by SPR method	Targeting the Nerve Growth Factor (NGF) Pathway in Drug Discovery. Potential Applications to New Therapies for Chronic Pain. — J Med Chem

Cellosaurus cell lines

10 cell lines: 4 cancer cell line, 3 somatic stem cell, 2 stromal cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B219	OP9/N	Stromal cell line	Sex unspecified
CVCL_B220	OP9/N-DLL1	Stromal cell line	Sex unspecified
CVCL_B976	TSt-4/N	Somatic stem cell	Sex unspecified
CVCL_B977	TSt-4/N-DLL1	Somatic stem cell	Sex unspecified
CVCL_C6VX	MSOD-B	Telomerase immortalized cell line	Female
CVCL_D8RB	Ubigene HCT 116 NGFR KO	Cancer cell line	Male
CVCL_TA68	HAP1 NGFR (-) 1	Cancer cell line	Male
CVCL_TA69	HAP1 NGFR (-) 2	Cancer cell line	Male
CVCL_VP74	TSt-4/N-DLL4	Somatic stem cell	Sex unspecified
CVCL_YU10	SK-OV-3-hCD271	Cancer cell line	Female

Clinical trials (associated diseases)

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