NTF3

Chr 12

neurotrophin 3

Also known as: HDNF, NGF-2, NGF2, NT-3, NT3

NCBI Gene: 4908ENSG00000185652UniProt: P20783

This gene encodes neurotrophin-3, a growth factor that promotes survival of sensory neurons including proprioceptive and visceral neurons and controls neuronal survival and differentiation during development. Mutations cause autosomal dominant congenital insensitivity to pain with anhidrosis and peripheral neuropathy affecting sensory and autonomic function. The gene is highly constrained against loss-of-function variants (pLI 0.93, LOEUF 0.37), indicating intolerance to protein-truncating mutations.

Summary from RefSeq, UniProt
Research Assistant →
12
Active trials
13
Pubs (1 yr)
51
P/LP submissions
0%
P/LP missense
0.37
LOEUF
LOF
Mechanism· predicted
Clinical Summary— NTF3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
51 unique Pathogenic / Likely Pathogenic· 32 VUS of 92 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.37LOEUF
pLI 0.932
Z-score 3.08
OE 0.08 (0.03–0.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.74Z-score
OE missense 0.63 (0.54–0.74)
108 obs / 172.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.03–0.37)
0≤0.351.4
Missense OE0.63 (0.54–0.74)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 1 / 13.0Missense obs/exp: 108 / 172.1Syn Z: 0.42
DN
0.4785th %ile
GOF
0.2298th %ile
LOF
0.72top 10%

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

LOFprediction above median · LOEUF 0.37

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

92 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic3
VUS32
Likely Benign1
Benign5
48
Pathogenic
3
Likely Pathogenic
32
VUS
1
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
48
0
48
Likely Pathogenic
0
0
3
0
3
VUS
0
25
7
0
32
Likely Benign
0
0
0
1
1
Benign
0
1
0
4
5
Total02658589

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

View in ClinVar →

Protein Context — Lollipop Plot

NTF3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
Relapsing Remitting Multiple Sclerosis (RRMS)

Indole-3-PROpionic Acid Clinical Trials - Multiple Sclerosis

RECRUITING
NCT07318129Phase NAGlostrup University Hospital, CopenhagenStarted 2026-01-26
PlaceboIndole-3-propionic acid (IPA)
Parkinson Disease

To Evaluate the Dose-response Effects of a Defined Volume of Physical Exercise on the Change of Peripheral Biomarkers, Clinical Response and Brain Connectivity in Parkinson's Disease: a Prospective, Observational, Cohort Pilot Study

RECRUITING
NCT06339398Casa di Cura San Raffaele CassinoStarted 2025-02-11
Aerobic exercise
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
Cancer

Onco Move - Improvement of Psychophysical Fitness in Adult Cancer Survivors

NOT YET RECRUITING
NCT07087652Phase NAGdansk University of Physical Education and SportStarted 2025-09-01
Onco Move multicomponent face-to-face training program
Alzheimer DiseaseInactivityPreventive Therapy

The Link Between Physical Activity and Brain Health in Healthy Adults

RECRUITING
NCT07025070Technical University of MadridStarted 2024-11-25
Ischemic Stroke, AcuteSleep Disorders, Circadian Rhythm

The Role of Circadian Factors in Regulation of Neuroplasticity in Ischemic Stroke (Interventional)

RECRUITING
NCT05247125Phase PHASE4Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of HealthStarted 2022-03-01
Blue light exposure + Melatonin treatmentMelatonin treatmentBlue light exposure
Fibromyalgia (FM)tDCSDuloxetine

Home-based Transcranial Direct Current Stimulation (tDCS) Compared to Duloxetine: Non-inferiority Clinical Trial (FIBROSTIM)

RECRUITING
NCT07203339Phase NAHospital de Clinicas de Porto AlegreStarted 2025-09-30
Transcranial direct current stimulation (tDCS) plus placebo.Duloxetine (60 mg) once dailyHome-based transcranial direct current stimulation
Preterm BirthMother-Infant InteractionInfant Development

Continuous Delivery Room Skin-to-skin-study for Moderate and Late Preterm Infants

RECRUITING
NCT05975203Phase NAUniversity of CologneStarted 2023-08-04
skin-to-skin contact
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet
Alzheimer's DiseaseMild Cognitive Impairment

A Clinical Trial of AAV2-BDNF Gene Therapy in Early Alzheimer's Disease and Mild Cognitive Impairment

RECRUITING
NCT05040217Phase PHASE1Mark TuszynskiStarted 2022-02-07
AAV2-BDNF Gene TherapyAAV2-BDNF Gene Therapy
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Discovery metabolomics and genetic analysis reveal lipid pathway alterations associated with malignant phenotype acquisition in pleomorphic adenoma and a novel NTF3::ITPR2 fusion in carcinoma ex pleomorphic adenoma.
de Lima-Souza RA et al.·Virchows Arch
2025
EDN1 and NTF3 in keloid pathogenesis: computational and experimental evidence as novel diagnostic biomarkers for fibrosis and inflammation.
Gong H et al.·Front Genet
2025Open Access
miR-21 promotes cervical cancer by regulating NTF3.
Chen Y et al.·Sci Rep
2025Open Access
Identification of unique binding mode anti-NTF3 antibodies from a novel long VH CDR3 phage display library.
Chin SE et al.·SLAS Discov
2025
Esketamine Provides Neuroprotection After Intracerebral Hemorrhage in Mice via the NTF3/PI3K/AKT Pathway.
Niu X et al.·CNS Neurosci Ther
2024Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients