BDNF
brain derived neurotrophic factor, the group of Neurotrophins
Basic information
Region (hg38): 11:27654892-27722058
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Central hypoventilation syndrome, congenital | AD | Neurologic | Early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality | Neurologic | 10390427; 11840487; 20301600 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (27 variants)
- Inborn genetic diseases (9 variants)
- not specified (7 variants)
- Obesity (3 variants)
- (1 variants)
- Congenital central hypoventilation (1 variants)
- Variant of unknown significance (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the BDNF gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | 4 | 11 | |||
| missense | 1 | 11 | 2 | 4 | 18 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 1 | 1 | 2 | |||
| splice variant | 0 | |||||
| non coding | 2 | 9 | 11 | |||
| Total | 0 | 2 | 14 | 10 | 17 |
Variants in BDNF
This is a list of pathogenic ClinVar variants found in the BDNF region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 11-27657922-C-T | Uncertain significance (Oct 01, 2022) | |||
| 11-27657923-G-A | Likely benign (Dec 31, 2019) | |||
| 11-27657926-C-T | Benign (Dec 31, 2019) | |||
| 11-27657956-A-G | Likely benign (Oct 25, 2022) | |||
| 11-27658008-C-T | Obesity | Likely pathogenic (Oct 13, 2020) | ||
| 11-27658019-G-A | Benign (Sep 07, 2022) | |||
| 11-27658063-C-A | Inborn genetic diseases | Likely pathogenic (Dec 20, 2016) | ||
| 11-27658082-G-A | Likely benign (Apr 17, 2018) | |||
| 11-27658082-G-T | Likely benign (Oct 24, 2018) | |||
| 11-27658115-C-T | Benign (Jul 23, 2022) | |||
| 11-27658115-C-C | not specified | Benign (Oct 30, 2022) | ||
| 11-27658118-C-T | Inborn genetic diseases | Likely benign (Oct 18, 2022) | ||
| 11-27658148-G-A | Likely benign (Sep 13, 2017) | |||
| 11-27658199-C-A | Uncertain significance (Jun 01, 2022) | |||
| 11-27658242-A-T | Uncertain significance (Oct 14, 2022) | |||
| 11-27658244-G-C | Benign (Aug 16, 2018) | |||
| 11-27658292-C-T | Likely benign (Jun 19, 2022) | |||
| 11-27658332-C-T | Inborn genetic diseases | Uncertain significance (Dec 03, 2021) | ||
| 11-27658342-G-C | Inborn genetic diseases | Likely benign (Jun 17, 2022) | ||
| 11-27658369-C-T | Memory impairment, susceptibility to • not specified | Benign (Oct 30, 2022) | ||
| 11-27658381-T-C | Inborn genetic diseases | Uncertain significance (Apr 07, 2022) | ||
| 11-27658395-G-T | Inborn genetic diseases | Uncertain significance (Feb 10, 2022) | ||
| 11-27658401-C-A | Inborn genetic diseases | Uncertain significance (Sep 14, 2021) | ||
| 11-27658437-A-G | Inborn genetic diseases | Uncertain significance (Feb 03, 2022) | ||
| 11-27658495-C-T | Inborn genetic diseases | Uncertain significance (May 04, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| BDNF | protein_coding | protein_coding | ENST00000438929 | 2 | 67166 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.656 | 0.343 | 125584 | 0 | 1 | 125585 | 0.00000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.94 | 108 | 181 | 0.595 | 0.0000107 | 2151 |
| Missense in Polyphen | 33 | 83.832 | 0.39364 | 961 | ||
| Synonymous | 0.0893 | 72 | 73.0 | 0.987 | 0.00000480 | 652 |
| Loss of Function | 2.69 | 2 | 12.1 | 0.165 | 8.93e-7 | 129 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000616 | 0.0000616 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability. {ECO:0000269|PubMed:12553913}.;
- Disease
- DISEASE: Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. {ECO:0000269|PubMed:11840487}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Alcoholism - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;Follicle Stimulating Hormone (FSH) signaling pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Spinal Cord Injury;MECP2 and Associated Rett Syndrome;BDNF-TrkB Signaling;MAPK Signaling Pathway;ERK Pathway in Huntington,s Disease;Selective serotonin reuptake inhibitors lead to several adverse outcomes;PI3K-Akt Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signal Transduction;role of erk5 in neuronal survival pathway;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;BDNF activates NTRK2 (TRKB) signaling;Activated NTRK2 signals through RAS;Activated NTRK2 signals through PLCG1;Activated NTRK2 signals through FYN;Activated NTRK2 signals through CDK5;Signaling by NTRK2 (TRKB);Signaling by NTRKs;BDNF;SHP2 signaling;Posttranslational regulation of adherens junction stability and dissassembly;Activated NTRK2 signals through FRS2 and FRS3;GPCR signaling-G alpha i;Signaling by Receptor Tyrosine Kinases;Neurotrophic factor-mediated Trk receptor signaling;p75(NTR)-mediated signaling
(Consensus)
Recessive Scores
- pRec
- 0.821
Intolerance Scores
- loftool
- 0.212
- rvis_EVS
- 0.44
- rvis_percentile_EVS
- 77.57
Haploinsufficiency Scores
- pHI
- 0.874
- hipred
- Y
- hipred_score
- 0.797
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.807
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Bdnf
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; normal phenotype; 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); reproductive system phenotype; vision/eye phenotype; hearing/vestibular/ear 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); digestive/alimentary phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; taste/olfaction 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); growth/size/body region phenotype; craniofacial phenotype;
Zebrafish Information Network
- Gene name
- bdnf
- Affected structure
- ventral mandibular arch
- Phenotype tag
- abnormal
- Phenotype quality
- malformed
Gene ontology
- Biological process
- transmembrane receptor protein tyrosine kinase signaling pathway;activation of phospholipase C activity;nervous system development;axon guidance;synapse assembly;peripheral nervous system development;memory;regulation of signaling receptor activity;negative regulation of myotube differentiation;nerve development;brain-derived neurotrophic factor receptor signaling pathway;positive regulation of brain-derived neurotrophic factor receptor signaling pathway;nerve growth factor signaling pathway;negative regulation of neuron apoptotic process;regulation of neuron differentiation;neurotrophin TRK receptor signaling pathway;collateral sprouting;positive regulation of collateral sprouting;neuron projection morphogenesis;modulation of chemical synaptic transmission;positive regulation of synapse assembly;positive regulation of receptor binding;positive regulation of non-membrane spanning protein tyrosine kinase activity;regulation of protein localization to cell surface
- Cellular component
- extracellular region;extracellular space;cytoplasm;mitochondrion;synaptic vesicle;nuclear speck;axon;dendrite;cytoplasmic vesicle;perinuclear region of cytoplasm
- Molecular function
- protein binding;growth factor activity