NGF

Chr 1AR

nerve growth factor

Also known as: Beta-NGF, HSAN5, NGFB

NGF encodes nerve growth factor, a secreted protein essential for the development and maintenance of sympathetic and sensory nervous systems that functions as a ligand for neurotrophin receptors. Mutations cause hereditary sensory and autonomic neuropathy type 5 (HSAN5), which follows autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants (pLI = 0.82, LOEUF = 0.53), reflecting its critical role in nervous system function.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismARLOEUF 0.531 OMIM phenotype
Clinical SummaryNGF
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Gene-Disease Validity (ClinGen)
hereditary sensory and autonomic neuropathy · ARStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
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ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 112 VUS of 200 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — NGF
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.820
Z-score 2.21
OE 0.00 (0.000.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.90Z-score
OE missense 0.80 (0.690.93)
127 obs / 159.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.53)
00.351.4
Missense OE0.80 (0.690.93)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 0 / 5.7Missense obs/exp: 127 / 159.1Syn Z: -1.06
DN
0.4884th %ile
GOF
0.1899th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS112
Likely Benign61
Benign8
Conflicting11
7
Pathogenic
1
Likely Pathogenic
112
VUS
61
Likely Benign
8
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
6
0
7
Likely Pathogenic
0
0
1
0
1
VUS
3
104
4
1
112
Likely Benign
0
3
4
54
61
Benign
0
1
5
2
8
Conflicting
11
Total41082057200

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NGF · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Parkinson's Disease

GDNF Gene Therapy for Parkinson's Disease

ACTIVE NOT RECRUITING
NCT04167540Phase PHASE1Brain Neurotherapy Bio, Inc.Started 2020-04-01
AAV2-GDNF
AgingCardiovascular Risk Factor

A Combined Multidomain Intervention to Prevent Cognitive Decline Associated With Cardiovascular Risk Factors.

RECRUITING
NCT04962061Phase NALouis BhererStarted 2021-09-01
Cognitive TrainingAerobic and resistance exercisesStretching and Toning
Circadian RhythmPostoperative Sleep Disturbance

Effect of Esketamine on Postoperative Sleep in Postmenopausal Women

NOT YET RECRUITING
NCT07315074Phase NAZhuan ZhangStarted 2026-03-01
EsketamineNormal Saline
GanglioneuroblastomaLocalized Resectable NeuroblastomaLocalized Unresectable Neuroblastoma

Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma

ACTIVE NOT RECRUITING
NCT00904241Children's Oncology GroupStarted 2000-11-06
Cytology Specimen Collection ProcedureLaboratory Biomarker Analysis
Physiological AdaptationsSport PerformanceAerobic Capacity

Molecular Hydrogen Inhalation: Effects on Health, Exercise Capacity and Inflammatory Response - in Vivo/in Vitro Studies

NOT YET RECRUITING
NCT07130942Phase NAGdansk University of Physical Education and SportStarted 2025-10-01
Inhalation using a molecular hydrogen generator
Huntington Disease

Study of BDNF Pathway Biomarkers in the Cerebrospinal Fluid in Patients With Huntington's Disease

RECRUITING
NCT04012411Phase NAUniversity Hospital, MontpellierStarted 2020-03-03
Brain MRILumbar PunctionBlood sample
Cutaneous Squamous Cell Carcinoma (CSCC)

Next-gen Flow Cytometry to Find Immune Profiles, Treatment Response, and Toxicity Markers in Skin Cancer Patients Treated With Cemiplimab.

RECRUITING
NCT07064330Instituto de Investigación Biomédica de SalamancaStarted 2025-07-17
Cemiplimab
RETT Syndrome With Proven MECP2 Mutation

Repurposing Mirtazapine in Rett Syndrome

RECRUITING
NCT07430046Phase PHASE2University of TriesteStarted 2025-07-09
mirtazapine
Late-Life Depression

Effects of Specific Amino Acid Supplementation and Lifestyle Factors on Brain Ageing

RECRUITING
NCT07497347Phase NAIRCCS Centro San Giovanni di Dio FatebenefratelliStarted 2026-03-01
L-serine supplementationPlacebo
Chronic Widespread PainFibromyalgia (FM)

The Added Value of Transcranial Direct Current Stimulation (tDCS) During Exercise for People With Chronic Widespread Pain

RECRUITING
NCT07212829Phase NAVrije Universiteit BrusselStarted 2026-02-01
Active tDCSAerobic exerciseSham tDCS
Carcinoma, Non-Small-Cell Lung

LIquid BIopsies in Patients Presenting Non-small Cell Lung Cancer

RECRUITING
NCT02511288Centre Leon BerardStarted 2015-07
Treatment Resistant DepressionMajor Depressive EpisodeMajor Depression

University of Iowa Interventional Psychiatry Service Patient Registry

RECRUITING
NCT04480918Mark NiciuStarted 2020-11-02
Electroconvulsive Therapy (ECT)Transcranial Magnetic Stimulation (TMS)Ketamine
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗