BDNF

protein-coding

brain derived neurotrophic factor, the group of Neurotrophins

Gene summary

This gene encodes a member of the nerve growth factor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. Binding of this protein to its cognate receptor promotes neuronal survival in the adult brain. Expression of this gene is reduced in Alzheimer's, Parkinson's, and Huntington's disease patients. This gene may play a role in the regulation of the stress response and in the biology of mood disorders. [provided by RefSeq, Nov 2015]

MANE transcript

NM_001709.5

Inheritance

ClinVar variants

P:2U:56B:33

Top phenotype

Central hypoventilation syndrome, congenital

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr11:27,654,893-27,722,058

External References & Databases

Ensembl (ENSG00000176697)

Transcript & Mutation Effects

hg38 • Region Span ~67.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Central hypoventilation syndrome, congenitalAD

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Early recognition and interventions to support ventilation (as well as avoidance of exacerbating factors) can reduce morbidity and mortality

Refs: 10390427; 11840487; 20301600

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BDNF variants in ClinVar

7 Conditions Cataloged

BDNF-related disorderTotal: 75

not providedTotal: 31

Inborn genetic diseasesTotal: 21

not specifiedTotal: 5

ObesityTotal: 3

Inherited obesityTotal: 1

Congenital central hypoventilationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001709.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	27 clinvar	4 clinvar	34
missense		1 clinvar	49 clinvar	2 clinvar		52
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	2	56	29	4	91

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001709.5	RefSeq	NP_001700.2	1	MANE Select
ENST00000356660.9	Ensembl	ENSP00000349084.4	1	MANE Select
NM_001143805.1	RefSeq	NP_001137277.1	1	Standard
NM_001143806.1	RefSeq	NP_001137278.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bdnf	Danio rerio	Structure: ventral mandibular arch Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

bdnf

Danio rerio

Structure: ventral mandibular arch

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

transmembrane receptor protein tyrosine kinase signaling pathway
activation of phospholipase C activity
nervous system development
axon guidance
synapse assembly

Molecular Function

protein binding
growth factor activity

Cellular Component

extracellular region
extracellular space
cytoplasm
mitochondrion
synaptic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000438929
Coding exons: 2
Length: 67166
Individuals with no LoFs: 125584
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125585
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.94	108	181	0.595	0.0000107	2151
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.821

Intolerance Scores

LoFtool: 0.212
RVIS EVS: 0.44
RVIS percentile EVS: 77.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.807

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium