BDNF

brain derived neurotrophic factor, the group of Neurotrophins

Basic information

Region (hg38): 11:27654892-27722058

Links

ENSG00000176697 ∙ NCBI:627 ∙ OMIM:113505 ∙ HGNC:1033 ∙ Uniprot:P23560 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the BDNF gene.

• not provided (27 variants)
• BDNF-related condition (16 variants)
• Inborn genetic diseases (9 variants)
• not specified (6 variants)
• Obesity (2 variants)
• Congenital central hypoventilation (1 variants)
• Memory impairment, susceptibility to (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.

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				8	4	12
missense		1	23		2	26
nonsense		1				1
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1		9	10
Total	0	2	27	8	15

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)
11-27657906-A-G		BDNF-related disorder	Uncertain significance (Jan 26, 2023)
11-27657922-C-T			Uncertain significance (Oct 01, 2022)
11-27657923-G-A			Likely benign (May 30, 2023)
11-27657926-C-T			Benign (Dec 02, 2023)
11-27657954-CA-C			Uncertain significance (Mar 12, 2023)
11-27657956-A-G			Likely benign (Oct 23, 2023)
11-27658008-C-T		Obesity	Likely pathogenic (Oct 13, 2020)
11-27658019-G-A		BDNF-related disorder	Benign/Likely benign (May 11, 2023)
11-27658063-C-A		Inborn genetic diseases	Likely pathogenic (Dec 20, 2016)
11-27658082-G-A		BDNF-related disorder	Likely benign (Sep 18, 2019)
11-27658082-G-T			Likely benign (Oct 24, 2018)
11-27658085-C-T		BDNF-related disorder	Likely benign (Jul 16, 2021)
11-27658100-A-G		BDNF-related disorder	Likely benign (Apr 27, 2021)
11-27658115-C-T		not specified	Benign (Dec 11, 2023)
11-27658115-C-C		not specified	Benign (Jan 31, 2024)
11-27658118-C-T		Inborn genetic diseases • BDNF-related disorder	Likely benign (Aug 04, 2023)
11-27658148-G-A			Likely benign (Sep 13, 2017)
11-27658199-C-A			Uncertain significance (Jun 01, 2022)
11-27658200-A-G		BDNF-related disorder	Uncertain significance (Jul 23, 2023)
11-27658242-A-T			Uncertain significance (Oct 14, 2022)
11-27658244-G-C			Benign (Dec 27, 2023)
11-27658256-C-T		BDNF-related disorder	Likely benign (Aug 14, 2020)
11-27658292-C-T		BDNF-related disorder	Likely benign (Jun 09, 2023)
11-27658307-G-A		BDNF-related disorder	Likely benign (May 11, 2023)

GnomAD

Source: gnomAD

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: 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

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