BDNF

brain derived neurotrophic factor, the group of Neurotrophins

Basic information

Region (hg38): 11:27654892-27722058

Links

ENSG00000176697NCBI:627OMIM:113505HGNC:1033Uniprot:P23560AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Central hypoventilation syndrome, congenitalADNeurologicEarly recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortalityNeurologic10390427; 11840487; 20301600

ClinVar

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

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.

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
1
clinvar
19
clinvar
3
clinvar
23
missense
1
clinvar
26
clinvar
2
clinvar
29
nonsense
1
clinvar
1
clinvar
2
start loss
0
frameshift
3
clinvar
1
clinvar
4
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
1
1
non coding
2
clinvar
1
clinvar
9
clinvar
12
Total 0 2 33 21 14

Variants in BDNF

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

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

Position Type Phenotype Significance ClinVar
11-27657874-T-C BDNF-related disorder Uncertain significance (Dec 12, 2023)2636918
11-27657906-A-G BDNF-related disorder Uncertain significance (Jan 26, 2023)2630210
11-27657922-C-T Uncertain significance (Oct 01, 2022)1298509
11-27657923-G-A Likely benign (May 30, 2023)771888
11-27657926-C-T Benign (Dec 02, 2023)718660
11-27657954-CA-C Uncertain significance (Mar 12, 2023)2845218
11-27657956-A-G Likely benign (Oct 23, 2023)2054554
11-27658008-C-T Obesity Likely pathogenic (Oct 13, 2020)981928
11-27658019-G-A BDNF-related disorder Benign/Likely benign (May 11, 2023)712726
11-27658063-C-A Inborn genetic diseases Likely pathogenic (Dec 20, 2016)521383
11-27658082-G-A BDNF-related disorder Likely benign (Sep 18, 2019)743862
11-27658082-G-T Likely benign (Oct 24, 2018)793495
11-27658085-C-T BDNF-related disorder Likely benign (Jul 16, 2021)3043298
11-27658100-A-G BDNF-related disorder Likely benign (Apr 27, 2021)3030169
11-27658115-C-T not specified Benign (Dec 11, 2023)783114
11-27658115-C-C not specified Benign (Jan 31, 2024)179329
11-27658118-C-T Inborn genetic diseases • BDNF-related disorder Likely benign (Aug 04, 2023)2309743
11-27658148-G-A Likely benign (Sep 13, 2017)709884
11-27658199-C-A Uncertain significance (Jun 01, 2022)2001803
11-27658200-A-G BDNF-related disorder Uncertain significance (Jul 23, 2023)2628764
11-27658242-A-T Uncertain significance (Oct 14, 2022)1962512
11-27658244-G-C Benign (Dec 27, 2023)736217
11-27658256-C-T BDNF-related disorder Likely benign (Aug 14, 2020)3045600
11-27658292-C-T BDNF-related disorder Likely benign (Jun 09, 2023)1572707
11-27658307-G-A BDNF-related disorder Likely benign (May 11, 2023)2759722

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BDNFprotein_codingprotein_codingENST00000438929 267166
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.6560.343125584011255850.00000398
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.941081810.5950.00001072151
Missense in Polyphen3383.8320.39364961
Synonymous0.08937273.00.9870.00000480652
Loss of Function2.69212.10.1658.93e-7129

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00006160.0000616
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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