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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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BDNF
brain derived neurotrophic factor
Chromosome 11 · 11p14.1
NCBI Gene: 627Ensembl: ENSG00000176697.21HGNC: HGNC:1033UniProt: A0A0E3SU01
2,558PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly Studied
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of synapse assemblypositive regulation of collateral sproutingprotein bindingcollateral sproutingobesityAbnormality of the skeletal systemsmoking initiationdiverticular disease
✦AI Summary

Brain-derived neurotrophic factor (BDNF) is a neurotrophic signaling molecule synthesized and secreted by excitatory neurons that plays a critical role in neuronal survival, maturation, and synaptic plasticity 1. BDNF activates signaling cascades primarily through the TrkB receptor and also via heterodimeric receptors formed by NGFR and SORCS2, with the latter pathway involved in synaptic plasticity, long-term depression, and neuronal apoptosis [UniProt]. Astrocytes actively participate in BDNF physiology by sensing extracellular BDNF through TrkB receptors and regulating BDNF uptake and recycling at synapses 2. BDNF is stored as proBDNF in presynaptic terminals and released upon neuronal activation; conversion of proBDNF to mature BDNF is crucial for neuronal function 1. Dysregulation of BDNF has been implicated in multiple neurodegenerative and psychiatric disorders. In Huntington's disease, the huntingtin protein controls BDNF synthesis and transport, with loss of BDNF contributing to disease manifestations 3. A common Val66Met polymorphism impairs activity-dependent BDNF secretion and is associated with memory deficits and psychiatric vulnerability 4. Reduced serum BDNF levels occur in Alzheimer's disease and mild cognitive impairment, with genetic polymorphisms and gender-specific effects 5. Imbalances between proBDNF and mature BDNF contribute to depression pathogenesis 6. Physical activity remains the most realistic intervention to maintain BDNF levels and cognitive function during aging 1.

Sources cited
1
BDNF is synthesized and secreted by excitatory neurons, stored with proBDNF in presynaptic terminals, and released upon neuronal activation; physical activity maintains BDNF levels
PMID: 40490314
2
Astrocytes sense extracellular BDNF through TrkB receptors and participate in BDNF uptake and recycling at synapses contributing to synaptic plasticity
PMID: 36780947
3
In Huntington's disease, huntingtin protein controls BDNF synthesis and transport, with loss of BDNF contributing to disease manifestations
PMID: 24668480
4
The Val66Met polymorphism impairs subcellular translocation and activity-dependent secretion of BDNF and is associated with impaired neurocognitive function and psychiatric disorders
PMID: 25824305
5
Serum BDNF levels are significantly lower in Alzheimer's disease and mild cognitive impairment, with BDNF Val66Met polymorphism and IL-1α polymorphisms involved in these changes
PMID: 36498925
6
Imbalances or inadequate conversion of proBDNF into mature BDNF impair neuronal plasticity, which is crucial to depression pathogenesis
PMID: 40359301
Disease Associationsⓘ20
obesityOpen Targets
0.60Moderate
Abnormality of the skeletal systemOpen Targets
0.56Moderate
smoking initiationOpen Targets
0.52Moderate
diverticular diseaseOpen Targets
0.51Moderate
type 2 diabetes mellitusOpen Targets
0.51Moderate
metabolic syndromeOpen Targets
0.44Moderate
SnoringOpen Targets
0.44Moderate
heart failureOpen Targets
0.43Moderate
sleep apneaOpen Targets
0.42Moderate
congestive heart failureOpen Targets
0.41Moderate
goutOpen Targets
0.41Moderate
overnutritionOpen Targets
0.40Weak
cancerOpen Targets
0.40Weak
mathematical abilityOpen Targets
0.39Weak
attention deficit hyperactivity disorderOpen Targets
0.39Weak
risk-taking behaviourOpen Targets
0.39Weak
smoking behaviorOpen Targets
0.39Weak
extrapyramidal and movement diseaseOpen Targets
0.37Weak
morbid obesityOpen Targets
0.36Weak
COVID-19Open Targets
0.35Weak
Pathogenic Variants2
NM_001709.5(BDNF):c.557G>A (p.Cys186Tyr)Likely pathogenic
Obesity
★☆☆☆2020→ Residue 186
NM_001709.5(BDNF):c.502G>T (p.Glu168Ter)Likely pathogenic
Inborn genetic diseases
★☆☆☆2016→ Residue 168
View on ClinVar ↗
Related Genes
SORT1Protein interaction100%FGFR2Protein interaction100%CNR1Protein interaction100%FGF3Protein interaction100%FGF5Protein interaction100%FGF7Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
51%
Lung
41%
Ovary
18%
Bone Marrow
15%
Liver
6%
Gene Interaction Network
Click a node to explore
BDNFSORT1FGFR2CNR1FGF3FGF5FGF7
PROTEIN STRUCTURE
Preparing viewer…
PDB1BND · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.23Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.05 [0.02–0.23]
RankingsWhere BDNF stands among ~20K protein-coding genes
  • #33of 20,598
    Most Researched2,558 · top 1%
  • #4,180of 5,498
    Most Pathogenic Variants2
  • #648of 17,882
    Most Constrained (LOEUF)0.23 · top 5%
Genes detectedBDNF
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Astrocytes and brain-derived neurotrophic factor (BDNF).
PMID: 36780947
Neurosci Res · 2023
1.00
2
The physiopathology of brain-derived neurotrophic factor.
PMID: 40490314
Physiol Rev · 2025
0.90
3
Brain-Derived Neurotrophic Factor, Nociception, and Pain.
PMID: 38785946
Biomolecules · 2024
0.90
4
Brain-Derived Neurotrophic Factor and Diabetes.
PMID: 32012942
Int J Mol Sci · 2020
0.80
5
Huntington's disease.
PMID: 24668480
Handb Exp Pharmacol · 2014
0.80