NRG1

Summary

NRG1 (neuregulin 1, HGNC:7997) is a protein-coding gene on chromosome 8p12, encoding Pro-neuregulin-1, membrane-bound isoform (Q02297). Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. In precision oncology, NRG1 Expression confers sensitivity to Patritumab in Lung Non-small Cell Carcinoma (CIViC Level B); 8 further curated variant–drug associations are listed below.

The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene through alternative promoter usage and splicing. These isoforms are expressed in a tissue-specific manner and differ significantly in their structure, and are classified as types I, II, III, IV, V and VI. Dysregulation of this gene has been linked to diseases such as cancer, schizophrenia, and bipolar disorder (BPD).

Source: NCBI Gene 3084 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hirschsprung disease (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 54
• Clinical variants (ClinVar): 70 total
• Phenotypes (HPO): 6
• Precision-oncology evidence (CIViC): 9 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Transcription factor: yes — 38 downstream targets (CollecTRI)
• MANE Select transcript: NM_013964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7997
Approved symbol	NRG1
Name	neuregulin 1
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	HRG, NDF, GGF
Ensembl gene	ENSG00000157168
Ensembl biotype	protein_coding
OMIM	142445
Entrez	3084

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 27 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000287842, ENST00000356819, ENST00000405005, ENST00000517967, ENST00000518084, ENST00000518206, ENST00000519240, ENST00000519301, ENST00000520407, ENST00000520502, ENST00000521670, ENST00000522402, ENST00000522569, ENST00000523041, ENST00000523079, ENST00000523320, ENST00000523534, ENST00000523681, ENST00000631040, ENST00000650819, ENST00000650856, ENST00000650866, ENST00000650919, ENST00000650964, ENST00000650967, ENST00000650980, ENST00000651149, ENST00000651175, ENST00000651333, ENST00000651335, ENST00000651696, ENST00000651807, ENST00000652588, ENST00000652592, ENST00000652698, ENST00000943676

RefSeq mRNA: 23 — MANE Select: NM_013964 NM_001159995, NM_001159996, NM_001159999, NM_001160001, NM_001160002, NM_001160004, NM_001160005, NM_001160007, NM_001160008, NM_001322197, NM_001322201, NM_001322202, NM_001322205, NM_001322206, NM_001322207, NM_004495, NM_013956, NM_013957, NM_013958, NM_013959, NM_013960, NM_013962, NM_013964

CCDS: CCDS47836, CCDS55218, CCDS55219, CCDS6083, CCDS6084, CCDS6085, CCDS6086, CCDS6087, CCDS75727, CCDS94271, CCDS94272, CCDS94273, CCDS94274, CCDS94275, CCDS94276, CCDS94277, CCDS94278

Canonical transcript exons

ENST00000405005 — 12 exons

Exon	Start	End
ENSE00001030853	32742008	32742075
ENSE00002117160	32548311	32548826
ENSE00003522619	32756403	32756529
ENSE00003542226	32759306	32759436
ENSE00003568919	32760200	32760406
ENSE00003573549	32727949	32728078
ENSE00003591274	32754372	32754474
ENSE00003644235	32616835	32616885
ENSE00003732872	32595828	32596005
ENSE00003743434	32614514	32614564
ENSE00003749649	32605562	32605683
ENSE00003850339	32763748	32774046

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1391 / max 618.4295, expressed in 1147 samples.

FANTOM5 promoters (30 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88363	8.1557	833
88383	1.4082	244
88362	0.7850	367
88371	0.5686	78
88361	0.5161	315
88365	0.3593	188
88376	0.2661	93
88364	0.2259	114
88382	0.1678	54
88341	0.1633	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.26	gold quality
ganglionic eminence	UBERON:0004023	98.27	gold quality
oocyte	CL:0000023	96.79	gold quality
secondary oocyte	CL:0000655	96.22	gold quality
monocyte	CL:0000576	91.01	gold quality
granulocyte	CL:0000094	90.64	gold quality
leukocyte	CL:0000738	90.56	gold quality
mononuclear cell	CL:0000842	90.52	gold quality
stromal cell of endometrium	CL:0002255	90.09	gold quality
dorsal root ganglion	UBERON:0000044	88.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.90	gold quality
endothelial cell	CL:0000115	86.70	silver quality
embryo	UBERON:0000922	86.69	gold quality
pons	UBERON:0000988	85.08	gold quality
cortical plate	UBERON:0005343	83.40	gold quality
colonic epithelium	UBERON:0000397	83.38	gold quality
trigeminal ganglion	UBERON:0001675	82.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.35	gold quality
sural nerve	UBERON:0015488	81.27	gold quality
buccal mucosa cell	CL:0002336	78.46	silver quality
left lobe of thyroid gland	UBERON:0001120	78.42	gold quality
thyroid gland	UBERON:0002046	77.89	gold quality
hypothalamus	UBERON:0001898	77.37	gold quality
sperm	CL:0000019	77.31	silver quality
prefrontal cortex	UBERON:0000451	77.10	gold quality
right lobe of thyroid gland	UBERON:0001119	76.60	gold quality
male germ cell	CL:0000015	76.54	silver quality
liver	UBERON:0002107	76.00	gold quality
endocervix	UBERON:0000458	75.91	gold quality
right lobe of liver	UBERON:0001114	75.42	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	6483.41
E-HCAD-25	yes	1628.53
E-HCAD-35	yes	1559.08
E-HCAD-11	yes	1206.98
E-ANND-3	yes	7.65
E-MTAB-6142	no	108.49

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

38 targets.

Target	Regulation
ADH4
ATP2C1
CCND3
CD44
CHD7
CHMP4B
CHRNE
CSN2
CTBP1
EGF
EGFR
EGR3
EMD
ERBB2
ERBB3
GHRHR
HGF
HSP90B2P
KDR
LGALS1
MAPK1
MMP9
MTA1
NGF
NOTCH1
NRG1
PA2G4
PAK1
PIK3C3
PIK3R1

Upstream regulators (CollecTRI, top): CEBPB, ESR2, GATA5, GDNF, NFKB, NRG1, RBPJ

miRNA regulators (miRDB)

161 targeting NRG1, 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-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426

Literature-anchored findings (GeneRIF, showing 40)

• Molecular determinants of the sensory and motor neuron-derived factor insertion into plasma membrane (PMID:11896060)
• HRG stimulation of mammary epithelial cells induces the expression of GADD153 mRNA and protein and transcription of GADD153 promoter. (PMID:12082616)
• the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia. (PMID:12145742)
• NRG-1 activates the JAK-STAT signal transduction pathway through its high-affinity receptor, the HER2/HER3 heterodimer. This pathway plays an important role in NRG-1-stimulated proliferation of pulmonary epithelial cells. (PMID:12204892)
• HRG-beta 1 could stimulate NF-kappa B nuclear translocation and DNA-binding activity via the I kappa B alpha phosphorylation-degradation mechanism (PMID:12471041)
• Association of neuregulin 1 with schizophrenia confirmed in a Scottish population (PMID:12478479)
• heregulin downregulates BRCA1 in the extracellular matrix of breast cancer cells (PMID:12509456)
• Synaptic loss, gliosis, inflammation, and neuronal death occurring in Alzheimer disease is associated with altered expression of NRG-1 and its receptors (the erbB membrane tyrosine kinases). (PMID:12528817)
• HRG up-regulation was sufficient for the development of mammary tumors in the absence of E2 stimulation (PMID:12556556)
• neuregulin-1 plays an important modulatory role in glioma cell invasion. (PMID:12600989)
• Segregation of receptor and ligand regulates activation of epithelial growth factor receptor; following a mechanical injury, heregulin-alpha activates erbB2 in cells at the edge of the wound, and this process hastens restoration of epithelial integrity (PMID:12646923)
• Betacellulin and heregulin/NDF-alpha are involved in epidermal morphogenesis and/or in maintenance of the differentiated phenotype. (PMID:12768307)
• A total of seven breakpoints are described that target the NRG1 gene on chromosome 8 in breast cancer and pancreatic cancer cell lines. (PMID:12800145)
• risk haplotype was more common in cases than controls (9.5 : 7.5%; P=0.04), and especially in our subset of 141 cases with a family history of schizophrenia (11.6%; P=0.019). (PMID:12808428)
• Linkage disequilibrium studies of 3 polymorphisms in schizophrenic Han Chinese families show the NRG1 gene may play a role in conferring susceptibility to schizphrenia. (PMID:12874607)
• No effect on the NRG-1 mRNA levels of this genotype at two SNPs previously associated with schizophrenia. (PMID:14569272)
• heregulin/HER system as a possible important physiologic growth regulatory system in melanocytes in which multiple deregulations may occur during progression toward melanoma, all resulting in, or indicating, growth factor independence. (PMID:14632199)
• Schizophrenia associated with 5’ polymorphisms in nrg1 in Chinese (PMID:14647391)
• no linkage of neuregulin 1 to schizophrenia in Japan (PMID:14699424)
• Mutations in the promoter region of NRG1 are associated with schizophrenia in the Chinese population. (PMID:14729827)
• ‘at-risk’ haplotype is positioned close to an EST cluster of unknown function (Hs.97362) within intron 1 of NRG1. (PMID:14966480)
• different haplotypes within the boundaries of the NRG1 gene may be associated with schizophrenia in the Han Chinese. (PMID:15007393)
• Heregulin regulates the ability of the ErbB3-binding protein Ebp1 to bind E2F promoter elements and repress E2F-mediated transcription (PMID:15073182)
• Stimulation of cells with neuregulin-1beta induced Ser-978 dephosphorylation, translocation of SSH1L onto F-actin-rich lamellipodia, and cofilin dephosphorylation. (PMID:15159416)
• This review summarizes recent findings that suggest involvement of altered NRG1-erbB signaling in the pathogenesis of schizophrenia. (PMID:15162166)
• If NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the Irish study of high-density schizophrenia families. (PMID:15197397)
• The data show a widespread expression of NRG-1 in the adult human brain, including, but not limited to, brain areas and cell populations implicated in schizophrenia. (PMID:15219675)
• NRG1 gene analysis was dominated by the presence of over-transmitted haplotypes. Data provides no evidence for a contribution of G72 to schizophrenia. (PMID:15248869)
• The association of neuregulin 1 polymorphisms in schizophrenia with and without deficit syndrome was investigated. Evidence supports NRG1 as a schizophrenia susceptibility gene. (PMID:15303101)
• Eight forms of Nrg-1 were expressed in cornea that differ by alternate use of four exons. This altered the predicted coding sequence in three domains of Nrg-1 which direct ligand/receptor interaction and trafficking, processing, and release of Nrg-1. (PMID:15326116)
• Breaks in NRG1 were detected in 6% (19 of 323) of breast cancers and in some lung and ovarian cancers. (PMID:15466169)
• before extracellular signal-regulated kinase activation and aquaporin synthesis, the membrane-bound prohormone neuregulin 1-beta is cleaved and binds to human epidermal growth factor receptor 3 (PMID:15498868)
• NRG1, with nine potential promoter, plays a central role in neural development and is most likely involved in regulation of synaptic plasticity, or how the brain responds or adapts to the environment. (PMID:15527969)
• Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the type III isoform SMDF variant in patients. (PMID:15545978)
• These results indicate that GGF2 is neurotrophic and neuroprotective for developing dopaminergic neurons and suggest a role for NRGs in repair of the damaged nigrostriatal system that occurs in Parkinson’s disease. (PMID:15584912)
• heregulin stimulates aggregation and inhibits invasion of MCF-7/6 cells via activation of the E-cadherin/catenin complex (PMID:15609326)
• Prolactin and heregulin override DNA damage-induced growth arrest and promote PI-3 kinase-dependent proliferation in breast cancer cells (PMID:15645137)
• One mechanism of HRG-regulated breast cancer cell proliferation, survival, and/or sensitivity to genotoxic damage is to stabilize and promote a nuclear accumulation of p21WAF1/CIP1 (PMID:15703820)
• autocrine and/or paracrine NRG-1/erbB signaling promotes neoplastic Schwann cell proliferation (PMID:15897877)
• NRG1 plays a role in increasing the genetic risk to positive symptoms of psychosis in a proportion of late onset Alzheimer’s disease families. (PMID:16082692)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrg1	ENSDARG00000104314
mus_musculus	Nrg1	ENSMUSG00000062991
rattus_norvegicus	Nrg1	ENSRNOG00000010392

Paralogs (3): NRG2 (ENSG00000158458), NRG4 (ENSG00000169752), NRG3 (ENSG00000185737)

Protein

Protein identifiers

Pro-neuregulin-1, membrane-bound isoform — Q02297 (reviewed: Q02297)

All UniProt accessions (21): Q02297, A0A024QY88, A0A494BZT4, A0A494C043, A0A494C054, A0A494C0K4, A0A494C0L9, A0A494C0Q4, A0A494C0T5, A0A494C114, A0A494C1B5, A0A494C1F5, A0A494C1F8, A0A494C1G2, A0A5F9ZHA5, E5RHP6, E5RHQ1, E5RIG8, H0YBA3, H0YCP0, H0YDC2

UniProt curated annotations — full annotation on UniProt →

Function. Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development. Binds to ERBB4. Binds to ERBB3. Acts as a ligand for integrins and binds (via EGF domain) to integrins ITGAV:ITGB3 or ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and ERRB3 are essential for NRG1-ERBB signaling. Induces the phosphorylation and activation of MAPK3/ERK1, MAPK1/ERK2 and AKT1. Ligand-dependent ERBB4 endocytosis is essential for the NRG1-mediated activation of these kinases in neurons.

Subunit / interactions. The cytoplasmic domain interacts with the LIM domain region of LIMK1. Forms a ternary complex with ERBB3 and ITGAV:ITGB3 or ITGA6:ITGB4. Interacts with NRDC and BACE1.

Subcellular location. Cell membrane Secreted Nucleus Secreted Membrane.

Tissue specificity. Type I isoforms are the predominant forms expressed in the endocardium. Isoform alpha is expressed in breast, ovary, testis, prostate, heart, skeletal muscle, lung, placenta liver, kidney, salivary gland, small intestine and brain, but not in uterus, stomach, pancreas, and spleen. Isoform 3 is the predominant form in mesenchymal cells and in non-neuronal organs, whereas isoform 6 is the major neuronal form. Isoform 8 is expressed in spinal cord and brain. Isoform 9 is the major form in skeletal muscle cells; in the nervous system it is expressed in spinal cord and brain. Also detected in adult heart, placenta, lung, liver, kidney, and pancreas. Isoform 10 is expressed in nervous system: spinal cord motor neurons, dorsal root ganglion neurons, and brain. Predominant isoform expressed in sensory and motor neurons. Not detected in adult heart, placenta, lung, liver, skeletal muscle, kidney, and pancreas. Not expressed in fetal lung, liver and kidney. Type IV isoforms are brain-specific.

Post-translational modifications. Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form. N- and O-glycosylated. Extensive glycosylation precedes the proteolytic cleavage.

Disease relevance. A chromosomal aberration involving NRG1 produces gamma-heregulin. Translocation t(8;11) with TENM4. The translocation fuses the 5’-end of TENM4 to NRG1 (isoform 8). The product of this translocation was first thought to be an alternatively spliced isoform. Gamma-heregulin is a soluble activating ligand for the ERBB2-ERBB3 receptor complex and acts as an autocrine growth factor in a specific breast cancer cell line (MDA-MB-175). Not detected in breast carcinoma samples, including ductal, lobular, medullary, and mucinous histological types, neither in other breast cancer cell lines.

Domain organisation. The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization. ERBB receptor binding is elicited entirely by the EGF-like domain.

Miscellaneous. Potential internal signal sequence at positions 76-100.

Similarity. Belongs to the neuregulin family.

Isoforms (11)

UniProt ID	Names	Canonical?
Q02297-1	1, Alpha	yes
Q02297-2	2, Alpha1A
Q02297-3	3, Alpha2B
Q02297-4	4, Alpha3
Q02297-6	6, Beta1, Beta1A
Q02297-7	7, Beta2
Q02297-8	8, Beta3, GGFHFB1
Q02297-9	9, GGF2, GGFHPP2
Q02297-10	10, SMDF
Q02297-11	11, Type IV-beta1a
Q02297-12	12

RefSeq proteins (23): NP_001153467, NP_001153468, NP_001153471, NP_001153473, NP_001153474, NP_001153476, NP_001153477, NP_001153479, NP_001153480, NP_001309126, NP_001309130, NP_001309131, NP_001309134, NP_001309135, NP_001309136, NP_004486, NP_039250, NP_039251, NP_039252, NP_039253, NP_039254, NP_039256, NP_039258* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002154	Neuregulin_C	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR018250	NRG1	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR040180	Neuregulin	Family

Pfam: PF00008, PF02158, PF07679

UniProt features (73 total): splice variant 16, strand 14, region of interest 5, compositionally biased region 5, sequence variant 5, sequence conflict 5, disulfide bond 4, glycosylation site 3, mutagenesis site 3, chain 2, topological domain 2, turn 2, helix 2, domain 2, propeptide 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7MN5	ELECTRON MICROSCOPY	2.93
3U7U	X-RAY DIFFRACTION	3.03
7MN6	ELECTRON MICROSCOPY	3.09
8U4L	ELECTRON MICROSCOPY	3.31
8U4I	ELECTRON MICROSCOPY	3.38
7MN8	ELECTRON MICROSCOPY	3.45
1HAE	SOLUTION NMR
1HAF	SOLUTION NMR
1HRE	SOLUTION NMR
1HRF	SOLUTION NMR
7SJL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02297-F1	56.85	0.17

Antibody-complex structures (SAbDab): 1 — 7MN8

Functional residue map

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

Catalytic / active sites (1): 34 (breakpoint for translocation to form gamma-heregulin)

Disulfide bonds (4): 57–112, 182–196, 190–210, 212–221

Glycosylation sites (3): 120, 126, 164

Mutagenesis-validated functional residues (3):

Position	Phenotype
181	defective in integrin-binding and in inducing erbb3 phosphorylation; when associated with or without e-185 or e-187. no
185	defective in integrin-binding and in inducing erbb3 phosphorylation; when associated with or without e-181 or e-187. no
187	defective in integrin-binding and in inducing erbb3 phosphorylation; when associated with or without e-181 or e-185. no

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-1227986	Signaling by ERBB2
R-HSA-1236394	Signaling by ERBB4
R-HSA-1250196	SHC1 events in ERBB2 signaling
R-HSA-1250342	PI3K events in ERBB4 signaling
R-HSA-1250347	SHC1 events in ERBB4 signaling
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1306955	GRB7 events in ERBB2 signaling
R-HSA-1358803	Downregulation of ERBB2:ERBB3 signaling
R-HSA-1963640	GRB2 events in ERBB2 signaling
R-HSA-1963642	PI3K events in ERBB2 signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6785631	ERBB2 Regulates Cell Motility
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8847993	ERBB2 Activates PTK6 Signaling
R-HSA-8863795	Downregulation of ERBB2 signaling
R-HSA-9620244	Long-term potentiation
R-HSA-9664565	Signaling by ERBB2 KD Mutants
R-HSA-9665686	Signaling by ERBB2 TMD/JMD mutants

MSigDB gene sets: 787 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, MODULE_516, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GGTGTGT_MIR329, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION

GO Biological Process (43): ventricular trabecula myocardium morphogenesis (GO:0003222), cell communication (GO:0007154), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), nervous system development (GO:0007399), brain development (GO:0007420), peripheral nervous system development (GO:0007422), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), neural crest cell development (GO:0014032), cell differentiation (GO:0030154), positive regulation of cell growth (GO:0030307), mammary gland development (GO:0030879), positive regulation of protein-containing complex assembly (GO:0031334), activation of protein kinase B activity (GO:0032148), intracellular signal transduction (GO:0035556), ERBB signaling pathway (GO:0038127), ERBB2 signaling pathway (GO:0038128), ERBB3 signaling pathway (GO:0038129), ERBB4 signaling pathway (GO:0038130), ERBB2-ERBB3 signaling pathway (GO:0038133), ERBB2-ERBB4 signaling pathway (GO:0038135), ERBB4-ERBB4 signaling pathway (GO:0038138), wound healing (GO:0042060), positive regulation of cell adhesion (GO:0045785), negative regulation of DNA-templated transcription (GO:0045892), negative regulation of secretion (GO:0051048), positive regulation of striated muscle cell differentiation (GO:0051155), cardiac muscle cell differentiation (GO:0055007), ventricular cardiac muscle cell differentiation (GO:0055012), positive regulation of cardiac muscle cell proliferation (GO:0060045), cardiac muscle cell myoblast differentiation (GO:0060379), endocardial cell differentiation (GO:0060956), positive regulation of ERK1 and ERK2 cascade (GO:0070374), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), positive regulation of peptidyl-tyrosine autophosphorylation (GO:1900086), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), signal transduction (GO:0007165), regulation of cell communication (GO:0010646), regulation of signaling (GO:0023051)

GO Molecular Function (14): transcription coregulator activity (GO:0003712), signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), integrin binding (GO:0005178), growth factor activity (GO:0008083), zinc ion binding (GO:0008270), nickel cation binding (GO:0016151), protein tyrosine kinase activator activity (GO:0030296), transmembrane receptor protein tyrosine kinase activator activity (GO:0030297), receptor tyrosine kinase binding (GO:0030971), ErbB-3 class receptor binding (GO:0043125), chemorepellent activity (GO:0045499), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), glutamatergic synapse (GO:0098978), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Signaling by ERBB2	7
Signaling by ERBB4	3
Signaling by Receptor Tyrosine Kinases	2
Signaling by ERBB2 in Cancer	2
Intracellular signaling by second messengers	1
Downregulation of ERBB2 signaling	1
PI3K/AKT Signaling in Cancer	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1
Signaling by PTK6	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signaling receptor binding	4
ERBB signaling pathway	3
receptor ligand activity	3
cellular anatomical structure	3
cellular process	2
system development	2
positive regulation of cellular process	2
signal transduction	2
transition metal ion binding	2
signaling receptor activator activity	2
ventricular cardiac muscle tissue morphogenesis	1
heart trabecula morphogenesis	1
enzyme-linked receptor protein signaling pathway	1
central nervous system development	1
animal organ development	1
head development	1
nervous system development	1
cell population proliferation	1
regulation of cell population proliferation	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
neural crest cell differentiation	1
stem cell development	1
cellular developmental process	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
gland development	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
activation of protein kinase activity	1
intracellular anatomical structure	1
cell surface receptor protein tyrosine kinase signaling pathway	1
transcription regulator activity	1
protein binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

19 interactions, top by confidence:

A	B	Type	Score
EGFR	NRG1	psi-mi:“MI:0915”(physical association)	0.550
NRG1	ERBB3	psi-mi:“MI:2364”(proximity)	0.480
S100A4	NRG1	psi-mi:“MI:0407”(direct interaction)	0.440
NRG1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
NRG1	ERBB4	psi-mi:“MI:0915”(physical association)	0.400
NRG1	FCAMR	psi-mi:“MI:0915”(physical association)	0.400
NRG1	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
NRG1	CHST10	psi-mi:“MI:0914”(association)	0.350
NRG1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
GLOD4	NRG1	psi-mi:“MI:0914”(association)	0.350
CDC5L		psi-mi:“MI:0914”(association)	0.350
NRG1	dnaE	psi-mi:“MI:0915”(physical association)	0.000
	NRG1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (178): NRG1 (Two-hybrid), MBOAT7 (Affinity Capture-MS), LSR (Affinity Capture-MS), PGAP1 (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), TMTC3 (Affinity Capture-MS), TMTC4 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), SLC38A10 (Affinity Capture-MS), ATP7B (Affinity Capture-MS), SLC35B2 (Affinity Capture-MS), NDUFA3 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1QT59, A2VEY9, A8X9H4, D3KZG3, O35412, O35607, O57474, O61366, O93383, P18861, P29415, P34535, P36383, P43322, P49414, P50605, P60571, P91682, Q02297, Q03345, Q05199, Q11069, Q13873, Q14693, Q2THW7, Q2THW9, Q2THX1, Q5R838, Q5RJX2, Q5YCC7, Q64448, Q69ZW3, Q6DR98, Q6H1V1, Q6IMP4, Q6TYA8, Q7TQ69, Q7Z5M5, Q86B91, Q8INR6

Diamond homologs: A0A6G9KJM3, A0A8U0LTM5, A0A8U0LTN3, A0A8U0LTT7, A0A8U0LTT9, A0A8U0LU66, D3ZUK3, O93383, P01132, P07522, P0DMY9, P0DMZ0, P0DQX9, P0DSL4, P49013, Q00968, Q01083, Q02297, Q5ZQU0, Q70E20, Q76CA1, Q8TER0, Q95ND4, A2AJ76, A2ASS6, D3YXG0, G4SLH0, O01761, O08775, O14511, O35136, O35181, O35569, O60469, O89026, P12960, P13591, P14781, P22063, P28685

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
NRG1	up-regulates	ERBB4	binding
NRG1	up-regulates	ERBB3	binding
NRG1	up-regulates	ERBB2	binding
NRG1	up-regulates	“ErbB receptor family”	binding
GDNF	“up-regulates quantity by expression”	NRG1	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — ESCA, PRCC, STAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	20
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4226 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:32595891:T:C	L55P	1.000
8:32595896:T:C	C57R	1.000
8:32595935:T:A	W70R	1.000
8:32595935:T:C	W70R	1.000
8:32595937:G:C	W70C	1.000
8:32595937:G:T	W70C	1.000
8:32605573:T:C	L97P	1.000
8:32605611:T:G	Y110D	1.000
8:32605617:T:A	C112S	1.000
8:32605617:T:C	C112R	1.000
8:32605618:G:C	C112S	1.000
8:32605619:C:G	C112W	1.000
8:32727990:T:A	C182S	1.000
8:32727991:G:C	C182S	1.000
8:32728014:T:A	C190S	1.000
8:32728014:T:C	C190R	1.000
8:32728015:G:A	C190Y	1.000
8:32728015:G:C	C190S	1.000
8:32728016:T:G	C190W	1.000
8:32728032:T:A	C196S	1.000
8:32728032:T:C	C196R	1.000
8:32728033:G:C	C196S	1.000
8:32728034:C:G	C196W	1.000
8:32728074:T:A	C210S	1.000
8:32728075:G:C	C210S	1.000
8:32742009:T:A	C212S	1.000
8:32742009:T:C	C212R	1.000
8:32742010:G:C	C212S	1.000
8:32742036:T:A	C221S	1.000
8:32742036:T:C	C221R	1.000

dbSNP variants (sampled 300 via entrez): RS1000002372 (8:32573709 T>A), RS1000002998 (8:31666727 A>T), RS1000006121 (8:31872812 G>C), RS1000011349 (8:32238091 G>A), RS1000013283 (8:32660917 T>C), RS1000013597 (8:32352389 G>T), RS1000016867 (8:32316006 C>G,T), RS1000019072 (8:32185261 T>C), RS1000023476 (8:32405929 T>A,C), RS1000024168 (8:31878134 A>G), RS1000027991 (8:32482436 C>G), RS1000028656 (8:32441606 G>A), RS1000032263 (8:31795106 A>G), RS1000033838 (8:32267788 T>G), RS1000034761 (8:31911219 C>A)

Disease associations

OMIM: gene MIM:142445 | disease phenotypes: MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
Hirschsprung disease	Moderate	Autosomal dominant
schizophrenia 6	Limited	Autosomal recessive
peripheral neuropathy	Limited	Autosomal dominant

Mondo (4): hereditary spastic paraplegia (MONDO:0019064), schizophrenia 6 (MONDO:0011280), peripheral neuropathy (MONDO:0005244), Hirschsprung disease (MONDO:0018309)

Orphanet (1): Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001977	Abnormal thrombosis
HP:0003581	Adult onset
HP:0004831	Recurrent thromboembolism
HP:0040227	Decreased level of histidine-rich glycoprotein
HP:0100724	Hypercoagulability

GWAS associations

54 associations (top):

Study	Trait	p-value
GCST000101_7	Hip geometry	2.000000e-07
GCST000334_1	Hirschsprung disease	2.000000e-08
GCST001066_23	Dialysis-related mortality	7.000000e-06
GCST001382_2	Thyroid cancer	2.000000e-09
GCST001776_3	Cardiac Troponin-T levels	5.000000e-06
GCST001856_12	Thyroid hormone levels	3.000000e-09
GCST001856_36	Thyroid hormone levels	2.000000e-08
GCST002097_29	Coronary artery calcification	9.000000e-06
GCST002119_23	Metabolite levels (X-11787)	3.000000e-06
GCST002658_6	Hirschsprung disease	3.000000e-07
GCST002685_14	Refractive astigmatism	2.000000e-06
GCST002707_13	Serum thyroid-stimulating hormone levels	8.000000e-06
GCST002774_22	Cognitive function	8.000000e-06
GCST002868_13	Response to serotonin reuptake inhibitors in major depressive disorder	1.000000e-06
GCST002945_10	Emphysema imaging phenotypes	1.000000e-06
GCST002945_29	Emphysema imaging phenotypes	5.000000e-07
GCST003012_1	Obstructive sleep apnea	5.000000e-06
GCST003265_152	Post bronchodilator FEV1/FVC ratio in COPD	3.000000e-06
GCST003265_155	Post bronchodilator FEV1/FVC ratio in COPD	4.000000e-06
GCST003265_447	Post bronchodilator FEV1/FVC ratio in COPD	2.000000e-06
GCST003265_466	Post bronchodilator FEV1/FVC ratio in COPD	7.000000e-07
GCST003265_473	Post bronchodilator FEV1/FVC ratio in COPD	5.000000e-06
GCST003764_4	Hirschsprung disease	1.000000e-11
GCST003988_19	Hypothyroidism	6.000000e-10
GCST003989_41	Chin dimples	2.000000e-09
GCST004070_2	Cerebrospinal P-tau181p levels	1.000000e-06
GCST004071_12	Cerebrospinal T-tau levels	6.000000e-06
GCST004744_52	Lung adenocarcinoma	1.000000e-10
GCST004748_132	Lung cancer	4.000000e-06
GCST004753_1	Papillary thyroid cancer	9.000000e-12

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004685	hip geometry
EFO:0005043	cardiac troponin T measurement
EFO:0004730	hormone measurement
EFO:0004723	coronary artery calcification
EFO:0005276	hydroxy-leucine measurement
EFO:0004337	intelligence
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007626	emphysema imaging measurement
EFO:0004713	FEV/FVC ratio
EFO:0004763	p-tau measurement
EFO:0004760	t-tau measurement
EFO:0007702	hip bone mineral density
EFO:0004874	memory performance
EFO:0005763	pulse pressure measurement
EFO:0008328	chronotype measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0004338	body weight
EFO:0004531	urate measurement
EFO:0007874	gut microbiome measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 9 predictive associations from 9 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
NRG1 Expression	Patritumab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID813
NRG1 Expression	Afatinib	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC C	EID7653
NRG1 Expression	Erlotinib + Gefitinib	Lung Non-small Cell Carcinoma	Resistance	CIViC C	EID7654
NRG1 Expression	Lapatinib	Head And Neck Squamous Cell Carcinoma	Sensitivity/Response	CIViC D	EID776
NRG1 Expression	Seribantumab	Ovarian Cancer	Sensitivity/Response	CIViC D	EID778
NRG1 Expression	Cisplatin + Gemcitabine + Carboplatin + Paclitaxel	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC D	EID779
NRG1 Expression	Anti-ErbB3 Monoclonal Antibody AV-203	Cancer	Sensitivity/Response	CIViC D	EID861
NRG1 Expression	Lapatinib	Breast Cancer	Resistance	CIViC D	EID1967
NRG1 Expression	Cetuximab	Colorectal Cancer	Resistance	CIViC D	EID777

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs13250975	Efficacy	3	antipsychotics	Schizophrenia
rs17716295	Efficacy	3	antipsychotics	Schizophrenia

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3924999	NRG1		0.00	0
rs13250975	NRG1	3	1.62	1	antipsychotics
rs17716295	NRG1	3	1.38	1	antipsychotics

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression, increases methylation	8
sodium arsenite	increases abundance, increases expression, increases phosphorylation, increases reaction, affects methylation (+2 more)	6
Arsenic	affects cotreatment, decreases expression, increases abundance, affects expression, affects methylation (+1 more)	5
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Doxorubicin	decreases expression, increases expression, decreases response to substance	3
Tobacco Smoke Pollution	affects expression, increases expression, increases methylation	3
Cyclosporine	increases expression	3
bisphenol A	affects methylation, affects cotreatment, increases methylation	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
U 0126	decreases activity, decreases phosphorylation, decreases reaction, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
bisphenol S	decreases expression, increases methylation	2
(+)-JQ1 compound	decreases expression	2
Resveratrol	increases phosphorylation, decreases expression, decreases reaction, increases expression	2
Fulvestrant	affects cotreatment, increases methylation, affects methylation, decreases reaction, increases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Air Pollutants	increases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Rotenone	increases expression, decreases expression	2
Silicon Dioxide	increases expression	2
Smoke	decreases expression, increases abundance	2
Tretinoin	increases expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, affects methylation	1
methylmercuric chloride	decreases expression	1

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1400	MDA-MB-175-VII	Cancer cell line	Female
CVCL_F1C1	MCF-7/HRG-S2	Cancer cell line	Female
CVCL_F1C2	MCF-7/HRG-T2	Cancer cell line	Female
CVCL_F1C3	MCF-7/HRG-T4	Cancer cell line	Female
CVCL_F1C4	MCF-7/HRG-T5	Cancer cell line	Female
CVCL_F1C6	MCF-7/HRG-T7	Cancer cell line	Female
CVCL_F1C7	MCF-7/HRG-T8	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	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	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	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)
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	PHASE3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	PHASE3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	PHASE3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	PHASE3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	PHASE3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	PHASE3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	PHASE3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	PHASE3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	PHASE3	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	PHASE3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	PHASE3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	PHASE3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	PHASE3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	PHASE3	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	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
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