NGF

nerve growth factor, the group of Neurotrophins

Basic information

Region (hg38): 1:115285904-115338770

Previous symbols: [ "NGFB" ]

Links

ENSG00000134259 ∙ NCBI:4803 ∙ OMIM:162030 ∙ HGNC:7808 ∙ Uniprot:P01138 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary sensory and autonomic neuropathy type 5 (Supportive), mode of inheritance: AR
• hereditary sensory and autonomic neuropathy type 5 (Strong), mode of inheritance: AR
• hereditary sensory and autonomic neuropathy type 5 (Limited), mode of inheritance: AD
• hereditary sensory and autonomic neuropathy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary sensory and autonomic, type V	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	14976160; 20978020
Insensivity to pain may result in injuries and infections

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NGF gene.

• Congenital sensory neuropathy with selective loss of small myelinated fibers (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NGF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	43	2	48
missense		1	93	4	1	99
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	4	5	10
Total	1	1	97	51	8

Variants in NGF

This is a list of pathogenic ClinVar variants found in the NGF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-115285950-A-C		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Jan 12, 2018)
1-115286090-T-G		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Nov 22, 2022)
1-115286109-A-G		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Jan 13, 2018)
1-115286113-GCC-G		Charcot-Marie-Tooth disease	Uncertain significance (-)
1-115286114-CCG-T		Congenital sensory neuropathy with selective loss of small myelinated fibers	Pathogenic (Oct 31, 2014)
1-115286115-C-G		NGF-related disorder	Likely benign (Sep 13, 2019)
1-115286115-C-T		Congenital sensory neuropathy with selective loss of small myelinated fibers	Likely benign (Sep 30, 2022)
1-115286116-G-T		Charcot-Marie-Tooth disease • Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Jan 25, 2019)
1-115286119-T-C			Uncertain significance (Oct 05, 2023)
1-115286124-C-T		not specified	Likely benign (Apr 04, 2017)
1-115286126-G-A		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (May 10, 2019)
1-115286131-A-C			Uncertain significance (Dec 22, 2016)
1-115286134-C-A		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Sep 24, 2019)
1-115286135-G-A		Congenital sensory neuropathy with selective loss of small myelinated fibers • not specified	Likely pathogenic (Mar 14, 2024)
1-115286139-G-A		Congenital sensory neuropathy with selective loss of small myelinated fibers	Likely benign (Jul 15, 2022)
1-115286151-G-A		Congenital sensory neuropathy with selective loss of small myelinated fibers	Likely benign (Jan 05, 2024)
1-115286158-A-G		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Sep 14, 2021)
1-115286164-A-G		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Mar 19, 2019)
1-115286166-C-T		Congenital sensory neuropathy with selective loss of small myelinated fibers	Likely benign (Jul 10, 2022)
1-115286183-G-C			Uncertain significance (Nov 01, 2021)
1-115286187-C-T		Congenital sensory neuropathy with selective loss of small myelinated fibers	Likely benign (Nov 29, 2020)
1-115286196-A-G		Congenital sensory neuropathy with selective loss of small myelinated fibers	Likely benign (Apr 11, 2023)
1-115286221-A-G		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Oct 03, 2021)
1-115286223-G-A		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Nov 13, 2021)
1-115286224-C-A		Congenital sensory neuropathy with selective loss of small myelinated fibers	Uncertain significance (Oct 05, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NGF	protein_coding	protein_coding	ENST00000369512	1	52319

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.820	0.176	125745	0	3	125748	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.903	127	159	0.798	0.0000109	1584
Missense in Polyphen		45	69.225	0.65006		655
Synonymous	-1.06	74	63.3	1.17	0.00000430	508
Loss of Function	2.21	0	5.67	0.00	3.27e-7	63

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival. Inhibits metalloproteinase dependent proteolysis of platelet glycoprotein VI (PubMed:20164177). {ECO:0000269|PubMed:20164177}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:14976160, ECO:0000269|PubMed:20978020, ECO:0000269|PubMed:22302274}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;nerve growth factor pathway (ngf);MAPK Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Prader-Willi and Angelman Syndrome;PI3K-Akt Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Activation of TRKA receptors;Signal Transduction;p75NTR signals via NF-kB;role of erk5 in neuronal survival pathway;phosphorylation of mek1 by cdk5/p35 down regulates the map kinase pathway;trka receptor signaling pathway;erk1/erk2 mapk signaling pathway;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;ARMS-mediated activation;Retrograde neurotrophin signalling;GPCR signaling-G alpha s Epac and ERK;NGF processing;Expression and Processing of Neurotrophins;TRKA activation by NGF;Signalling to RAS;Signalling to p38 via RIT and RIN;GPCR signaling-G alpha s PKA and ERK;Frs2-mediated activation;Prolonged ERK activation events;Signalling to ERKs;PLC-gamma1 signalling;Signaling by NTRK1 (TRKA);Signaling by NTRKs;BDNF;SHP2 signaling;NRIF signals cell death from the nucleus;NFG and proNGF binds to p75NTR;Signalling to STAT3;NRAGE signals death through JNK;PI3K/AKT activation;NADE modulates death signalling;NGF;p75NTR recruits signalling complexes;NF-kB is activated and signals survival;Death Receptor Signalling;Ceramide signalling;Axonal growth stimulation;p75NTR regulates axonogenesis;p75 NTR receptor-mediated signalling;GPCR signaling-G alpha i;Signaling by Receptor Tyrosine Kinases;Neurotrophic factor-mediated Trk receptor signaling;p75(NTR)-mediated signaling;Cell death signalling via NRAGE, NRIF and NADE;Trk receptor signaling mediated by PI3K and PLC-gamma;p75NTR negatively regulates cell cycle via SC1 (Consensus)

Recessive Scores

• pRec: 0.956

Intolerance Scores

• loftool: 0.0944
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.73

Haploinsufficiency Scores

• pHI: 0.150
• hipred: Y
• hipred_score: 0.828
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.693

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ngf
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: activation of MAPKK activity;activation of cysteine-type endopeptidase activity involved in apoptotic process;transmembrane receptor protein tyrosine kinase signaling pathway;peripheral nervous system development;memory;negative regulation of cell population proliferation;extrinsic apoptotic signaling pathway via death domain receptors;regulation of signaling receptor activity;positive regulation of gene expression;nerve development;nerve growth factor processing;nerve growth factor signaling pathway;positive regulation of apoptotic process;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of DNA binding;negative regulation of neuron apoptotic process;regulation of neuron differentiation;positive regulation of neuron differentiation;positive regulation of Ras protein signal transduction;neurotrophin TRK receptor signaling pathway;phosphatidylinositol-mediated signaling;positive regulation of collateral sprouting;neuron projection morphogenesis;positive regulation of axonogenesis;modulation of chemical synaptic transmission
• Cellular component: extracellular region;extracellular space;Golgi lumen;cytosol;synaptic vesicle;axon;dendrite;cytoplasmic vesicle
• Molecular function: nerve growth factor receptor binding;protein binding;growth factor activity;metalloendopeptidase inhibitor activity