BECN2

Summary

BECN2 (beclin 2, HGNC:38606) is a protein-coding gene on chromosome 1q43, encoding Beclin-2 (A8MW95). Involved in 2 distinct lysosomal degradation pathways: acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover.

Predicted to enable phosphatidylinositol 3-kinase binding activity and protein-macromolecule adaptor activity. Acts upstream of or within G protein-coupled receptor catabolic process; autophagy; and endosome to lysosome transport. Predicted to be located in cytoplasm. Predicted to be part of phosphatidylinositol 3-kinase complex, class III, type I and phosphatidylinositol 3-kinase complex, class III, type II. Predicted to be active in phagophore assembly site.

Source: NCBI Gene 441925 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 10 total — 1 pathogenic
• MANE Select transcript: NM_001290693

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:38606
Approved symbol	BECN2
Name	beclin 2
Location	1q43
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196289
Ensembl biotype	protein_coding
OMIM	615687
Entrez	441925

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000419583

RefSeq mRNA: 1 — MANE Select: NM_001290693 NM_001290693

CCDS: CCDS81433

Canonical transcript exons

ENST00000419583 — 1 exons

Exon	Start	End
ENSE00001707793	241957767	241959062

Expression profiles

Bgee: expression breadth not_expressed, 0 present calls, max score 37.20.

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
placenta	UBERON:0001987	35.44	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
liver	UBERON:0002107	30.64	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
tonsil	UBERON:0002372	28.77	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
leukocyte	CL:0000738	27.50	gold quality
monocyte	CL:0000576	27.49	gold quality
right coronary artery	UBERON:0001625	27.11	gold quality
urinary bladder	UBERON:0001255	26.63	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.00	gold quality
muscle of leg	UBERON:0001383	26.00	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
right lobe of liver	UBERON:0001114	25.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
gastrocnemius	UBERON:0001388	24.96	gold quality
calcaneal tendon	UBERON:0003701	24.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• Study identified a previously uncharacterized mammalian-specific protein, Beclin 2, which, like Beclin 1, functions in autophagy and interacts with class III PI3K complex components.[Beclin 2] (PMID:23954414)
• distinct patterns of Beclin 1 and Beclin 2 were associated with aggressive clinical outcomes. Beclin 1 overexpression, as well as Beclin 2 overexpression and depletion, contributed to tumor growth. (PMID:26506105)
• Both transfected and endogenous beclin 2 coimmunoprecipitated with vGPCR. Beclin 2 overexpression decreased HA-vGPCR steady-state levels. It regulates vGPCR levels by a lysosomal degradation pathway. (PMID:26929373)
• polar BECN2 CCD interface residues result in a metastable homodimer, facilitating dissociation, but enable better interactions with polar ATG14 residues stabilizing the BECN2:ATG14 heterodimer. (PMID:28218432)
• Further data showed that reactive oxygen species-c-Jun activation by HBx resulted in the release of beclin-1 from its association with beclin-2 to form a complex with VPS34, thus enhancing autophagosome formation. (PMID:28515304)
• Beclin 2 negatively regulates innate immune signaling and tumor development. (PMID:32865519)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	becn1	ENSDARG00000079128
mus_musculus	Becn2	ENSMUSG00000104158
rattus_norvegicus	Becn2	ENSRNOG00000038076
drosophila_melanogaster	Atg6	FBGN0264325
caenorhabditis_elegans		WBGENE00000247

Paralogs (1): BECN1 (ENSG00000126581)

Protein

Protein identifiers

Beclin-2 — A8MW95 (reviewed: A8MW95)

Alternative names: Beclin-1 autophagy-related pseudogene 1, Beclin-1-like protein 1

All UniProt accessions (1): A8MW95

UniProt curated annotations — full annotation on UniProt →

Function. Involved in 2 distinct lysosomal degradation pathways: acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover. Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1.

Subunit / interactions. Homodimer (via coiled-coil domain). Interacts (via coiled-coil domain) with ATG14 (via coiled-coil domain); this interaction is tighter than BECN2 self-association. Interacts with AMBRA1, UVRAG and PIK3C3/VPS34; these interactions are not disrupted by starvation. Does not interact with RUBCN. Interacts (via N-terminus) with GPRASP1/GASP1; the interaction is direct.

Subcellular location. Cytoplasm.

Tissue specificity. Present in fetal and adult brain (at protein level).

Similarity. Belongs to the beclin family.

RefSeq proteins (1): NP_001277622* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007243	Atg6/Beclin	Family
IPR038274	Atg6/Beclin_C_sf	Homologous_superfamily
IPR040455	Atg6_BARA	Domain
IPR041691	Atg6/beclin_CC	Domain

Pfam: PF04111, PF17675

UniProt features (15 total): mutagenesis site 10, region of interest 2, chain 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8GT9	X-RAY DIFFRACTION	2
5K7B	X-RAY DIFFRACTION	2.3
5K9L	X-RAY DIFFRACTION	2.52
8GU7	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MW95-F1	77.12	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (10):

Position	Phenotype
211	increases homodimerization. decreases interaction with atg14.
215	decreases interaction with atg14. increases slightly homodimerization; when associated with l-190.
222	decreases homodimerization. decreases interaction with atg14.
243	decreases homodimerization. decreases interaction with atg14.
80	abolishes interaction with gprasp1/gasp1 and ability to degrade g-protein coupled receptor. does not affect function in
173	decreases homodimerization. decreases interaction with atg14.
187	increases strongly homodimerization. decreases interaction with atg14.
190	decreases interaction with atg14. increases slightly homodimerization; when associated with l-215.
197	decreases interaction with atg14. probably strongly increases homodimerization; when associated with l-208.
208	decreases interaction with atg14. probably strongly increases homodimerization; when associated with l-197.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GOBP_LYSOSOMAL_TRANSPORT, GOBP_VACUOLE_ORGANIZATION, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MACROAUTOPHAGY, GOBP_RECEPTOR_METABOLIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY, GOBP_CARBOHYDRATE_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_STARVATION, chr1q43, GOBP_RECEPTOR_CATABOLIC_PROCESS, GOBP_AUTOPHAGOSOME_ORGANIZATION, GOBP_RESPONSE_TO_STARVATION

GO Biological Process (9): autophagosome assembly (GO:0000045), mitophagy (GO:0000423), autophagy (GO:0006914), cellular response to nitrogen starvation (GO:0006995), endosome to lysosome transport (GO:0008333), glucose homeostasis (GO:0042593), late endosome to vacuole transport (GO:0045324), G protein-coupled receptor catabolic process (GO:1990172), receptor catabolic process (GO:0032801)

GO Molecular Function (4): protein-macromolecule adaptor activity (GO:0030674), phosphatidylinositol 3-kinase binding (GO:0043548), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (4): phagophore assembly site (GO:0000407), phosphatidylinositol 3-kinase complex, class III, type I (GO:0034271), phosphatidylinositol 3-kinase complex, class III, type II (GO:0034272), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intercellular transport	2
vesicle-mediated transport	2
protein binding	2
binding	2
cellular anatomical structure	2
phosphatidylinositol 3-kinase complex, class III	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
autophagy of mitochondrion	1
macroautophagy	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cellular response to starvation	1
cellular response to nitrogen levels	1
lysosomal transport	1
carbohydrate homeostasis	1
vacuolar transport	1
receptor catabolic process	1
negative regulation of G protein-coupled receptor signaling pathway	1
macromolecule catabolic process	1
receptor metabolic process	1
molecular adaptor activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

906 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BECN2	PIK3C3	Q8NEB9	994
BECN2	BCL2	P10415	990
BECN2	ATG14	Q6ZNE5	982
BECN2	PIK3R4	Q99570	978
BECN2	BCL2L1	Q07817	849
BECN2	ATG5	Q9H1Y0	770
BECN2	BECN1	Q14457	734
BECN2	ATG7	O95352	724
BECN2	BNIP3	Q12983	715
BECN2	ATG12	O94817	708
BECN2	MAP1A	P78559	663
BECN2	MAP1LC3B	Q9GZQ8	654
BECN2	ATG3	Q9NT62	647
BECN2	EXOC8	Q8IYI6	618
BECN2	SQSTM1	Q13501	616

IntAct

8 interactions, top by confidence:

A	B	Type	Score
BECN2	GPRASP1	psi-mi:“MI:0915”(physical association)	0.580
GPRASP1	BECN2	psi-mi:“MI:0915”(physical association)	0.580
BECN2	BCL2	psi-mi:“MI:0915”(physical association)	0.400
BECN2	ATG14	psi-mi:“MI:0914”(association)	0.350
BECN2	LSM1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (14): ATG14 (Co-crystal Structure), ATG14 (Affinity Capture-Western), HMGB1 (Affinity Capture-Western), AMBRA1 (Affinity Capture-Western), KIAA0226 (Affinity Capture-Western), UVRAG (Affinity Capture-Western), GPRASP1 (Two-hybrid), TP53INP2 (Two-hybrid), CNR1 (Two-hybrid), ADRB2 (Two-hybrid), GPRASP1 (Affinity Capture-Western), BECN1P1 (Affinity Capture-Western), BECN1P1 (Affinity Capture-MS), GPRASP1 (Affinity Capture-Western)

ESM2 similar proteins: A2CI97, A5DIV5, A7MBC2, A8MW95, F1QNV4, J3QPZ5, O02799, O95822, P0DM65, P12617, P52630, Q0IHN5, Q1LXZ7, Q22592, Q2KJ22, Q3TBD2, Q3U1Y4, Q5F259, Q5FW14, Q5I0I8, Q5RB40, Q5U464, Q6DE55, Q6DHG8, Q6DKK2, Q6PBQ2, Q6UXN7, Q76LS9, Q7T0X5, Q86YJ7, Q8BHY2, Q8BWR8, Q8CDJ8, Q8HXG3, Q8IUC4, Q8K285, Q8K2H4, Q8TDY4, Q920F5, Q99J39

Diamond homologs: A5DIV5, A8MW95, I1S4N7, O88597, P0DM65, P87117, Q14457, Q22592, Q4A1L3, Q4A1L4, Q4A1L5, Q54JI9, Q55CC5, Q5R878, Q5ZKS6, Q6GP52, Q91XJ1, Q9VCE1, F1RCP1, Q9M367, W0TD11

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

10 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	5
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
153226	GRCh38/hg38 1q43(chr1:239288025-242458053)x1	Pathogenic

SpliceAI

181 predictions. Top by Δscore:

Variant	Effect	Δscore
1:241958690:GAG:G	donor_gain	0.7100
1:241958688:CAGAG:C	donor_loss	0.5900
1:241958689:AGAG:A	donor_loss	0.5900
1:241958691:AGGTA:A	donor_loss	0.5900
1:241958692:GG:G	donor_loss	0.5900
1:241958693:GT:G	donor_loss	0.5900
1:241958694:T:A	donor_loss	0.5900
1:241958729:G:GT	donor_gain	0.5500
1:241958687:TCAGA:T	donor_loss	0.5300
1:241958775:G:A	acceptor_gain	0.5300
1:241958853:G:GT	donor_gain	0.5300
1:241958774:T:TA	acceptor_gain	0.5100
1:241958695:A:T	donor_loss	0.4900
1:241958804:G:GG	donor_gain	0.4700
1:241958389:A:T	donor_gain	0.4500
1:241958405:GGAC:G	donor_gain	0.4500
1:241958508:G:GT	donor_gain	0.4500
1:241958803:A:AG	donor_gain	0.4400
1:241958545:TGG:T	donor_gain	0.4200
1:241958546:G:GA	donor_gain	0.4200
1:241958406:G:T	donor_gain	0.4100
1:241958728:TGAA:T	acceptor_gain	0.4100
1:241958729:GAAG:G	acceptor_gain	0.4100
1:241958867:GG:G	donor_gain	0.4000
1:241958868:GG:G	donor_gain	0.4000
1:241958783:GGAT:G	acceptor_gain	0.3900
1:241958690:G:GT	donor_gain	0.3800
1:241958859:GC:G	donor_gain	0.3800
1:241958731:A:AT	acceptor_gain	0.3600
1:241958662:T:TA	donor_loss	0.3500

AlphaMissense

2820 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:241958532:T:C	F256L	0.978
1:241958534:T:A	F256L	0.978
1:241958534:T:G	F256L	0.978
1:241957782:T:C	F6L	0.974
1:241957784:C:A	F6L	0.974
1:241957784:C:G	F6L	0.974
1:241958631:T:A	W289R	0.965
1:241958631:T:C	W289R	0.965
1:241959017:T:A	N417K	0.960
1:241959017:T:G	N417K	0.960
1:241959027:A:C	S421R	0.960
1:241959029:T:A	S421R	0.960
1:241959029:T:G	S421R	0.960
1:241958569:A:T	N268I	0.955
1:241958766:T:C	F334L	0.954
1:241958768:C:A	F334L	0.954
1:241958768:C:G	F334L	0.954
1:241958826:T:C	F354L	0.954
1:241958828:C:A	F354L	0.954
1:241958828:C:G	F354L	0.954
1:241958007:T:C	F81L	0.950
1:241958009:C:A	F81L	0.950
1:241958009:C:G	F81L	0.950
1:241958764:T:C	L333S	0.946
1:241958985:T:A	W407R	0.945
1:241958985:T:C	W407R	0.945
1:241957788:T:A	C8S	0.939
1:241957789:G:C	C8S	0.939
1:241958570:T:A	N268K	0.938
1:241958570:T:G	N268K	0.938

dbSNP variants (sampled 300 via entrez): RS1000761912 (1:241955920 AAAGTT>A), RS1001483677 (1:241959482 C>T), RS1001829667 (1:241959264 T>G), RS1002895011 (1:241958344 A>G), RS1003326168 (1:241958426 G>A), RS1003490420 (1:241957120 G>A,C), RS1003846118 (1:241956979 G>A), RS1004179305 (1:241958385 C>T), RS1004398758 (1:241958590 T>C), RS1004557999 (1:241956223 A>AG), RS1004674062 (1:241956577 T>C), RS1005165462 (1:241957177 C>A,T), RS1005384442 (1:241957370 C>T), RS1006169887 (1:241955958 G>A), RS1006389144 (1:241956135 A>G)

Disease associations

OMIM: gene MIM:615687 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
metarrestin	affects binding, decreases reaction, increases reaction	1
ginsenoside Rg2	affects binding, decreases reaction	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.