BECN1

protein-coding

beclin 1, the group of PIK3C3 complex subunits|Autophagy related|MicroRNA protein coding host genes

Gene summary

This gene encodes a protein that regulates autophagy, a catabolic process of degradation induced by starvation. The encoded protein is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking processes. This protein is thought to play a role in multiple cellular processes, including tumorigenesis, neurodegeneration and apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

MANE transcript

NM_001313998.2

Inheritance

—

ClinVar variants

U:44B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr17:42,810,134-42,833,350

External References & Databases

Ensembl (ENSG00000126581)

Transcript & Mutation Effects

hg38 • Region Span ~23.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BECN1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001313998.2. 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			1 clinvar	2 clinvar		3
missense			40 clinvar	1 clinvar		41
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	44	3	0	47

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001313998.2	RefSeq	NP_001300927.1	11	MANE Select
ENST00000590099.6	Ensembl	ENSP00000465364.1	11	MANE Select
NM_001313999.1	RefSeq	NP_001300928.1	10	Standard
NM_001314000.2	RefSeq	NP_001300929.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
becn1	Danio rerio	Structure: cell Quality: decreased process quality abnormal

Gene / Model

Organism

Observed Phenotype

becn1

Danio rerio

Structure: cell

Quality: decreased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Apoptosis - multiple species - Homo sapiens (human)
Autophagy - animal - Homo sapiens (human)
Autophagy - other - Homo sapiens (human)
Mitophagy - animal - Homo sapiens (human)

Biological Process

autophagosome assembly
autophagy of mitochondrion
mitophagy
response to hypoxia
autophagy

Molecular Function

protein binding
protein kinase binding
ubiquitin protein ligase binding
protein homodimerization activity
phosphatidylinositol 3-kinase binding

Cellular Component

phagophore assembly site
nucleus
mitochondrion
endosome
autophagosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361523
Coding exons: 11
Length: 23216
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125746
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.88	167	251	0.666	0.0000134	2989
Missense (PolyPhen)		59	96.85	0.60919		1203
Synonymous	2.12	70	96.5	0.725	0.00000540	810
Loss of Function	4.04	4	26.4	0.151	0.00000138	296

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000067	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a central role in autophagy (PubMed:23184933, PubMed:28445460). Acts as core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530, PubMed:26783301). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis (PubMed:25275521). Protects against infection by a neurovirulent strain of Sindbis virus (PubMed:9765397). May play a role in antiviral host defense. {ECO:0000269|PubMed:20208530, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:23184933, ECO:0000269|PubMed:25275521, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:28445460, ECO:0000269|PubMed:9765397, ECO:0000305}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.374
RVIS EVS: -0.18
RVIS percentile EVS: 39.95

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.886

Gene Damage Prediction

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