BAG2

Summary

BAG2 (BAG cochaperone 2, HGNC:938) is a protein-coding gene on chromosome 6p12.1, encoding BAG family molecular chaperone regulator 2 (O95816). Co-chaperone for HSP70 and HSC70 chaperone proteins.

BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The predicted BAG2 protein contains 211 amino acids. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner.

Source: NCBI Gene 9532 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total — 3 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:938
Approved symbol	BAG2
Name	BAG cochaperone 2
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112208
Ensembl biotype	protein_coding
OMIM	603882
Entrez	9532

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000370693, ENST00000965201

RefSeq mRNA: 1 — MANE Select: NM_004282 NM_004282

CCDS: CCDS4961

Canonical transcript exons

ENST00000370693 — 3 exons

Exon	Start	End
ENSE00000757340	57182032	57182141
ENSE00001453348	57183778	57189833
ENSE00001453368	57172326	57172810

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 96.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.3393 / max 290.7712, expressed in 1739 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68331	14.3947	1570
68334	9.3984	1527
68335	3.5640	1243
68336	1.1801	646
68332	0.5459	373
68333	0.2560	133

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	96.88	gold quality
heart right ventricle	UBERON:0002080	93.63	gold quality
biceps brachii	UBERON:0001507	92.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.61	gold quality
saphenous vein	UBERON:0007318	91.33	gold quality
seminal vesicle	UBERON:0000998	90.85	gold quality
smooth muscle tissue	UBERON:0001135	90.71	gold quality
diaphragm	UBERON:0001103	90.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.42	gold quality
myometrium	UBERON:0001296	90.41	gold quality
blood vessel layer	UBERON:0004797	88.97	gold quality
urethra	UBERON:0000057	88.31	gold quality
body of uterus	UBERON:0009853	87.92	gold quality
vena cava	UBERON:0004087	87.91	gold quality
myocardium	UBERON:0002349	87.74	gold quality
urinary bladder	UBERON:0001255	87.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.49	gold quality
lower esophagus	UBERON:0013473	87.43	gold quality
skeletal muscle tissue	UBERON:0001134	86.59	gold quality
popliteal artery	UBERON:0002250	86.46	gold quality
tibial artery	UBERON:0007610	86.44	gold quality
muscle tissue	UBERON:0002385	86.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.20	gold quality
vastus lateralis	UBERON:0001379	85.91	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.74	gold quality
aorta	UBERON:0000947	85.53	gold quality
deltoid	UBERON:0001476	85.39	silver quality
left ventricle myocardium	UBERON:0006566	85.20	gold quality
sigmoid colon	UBERON:0001159	85.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, MYC, SP1

miRNA regulators (miRDB)

86 targeting BAG2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-338-5P	99.92	72.34	2951

Literature-anchored findings (GeneRIF, showing 21)

• BAG2 was directly phosphorylated at serine 20 in vitro by MAPKAPK2 and MAPKAP2 is also required for phosphorylation of BAG2 in vivo. (PMID:15271996)
• BAG2 binds to the carboxyl terminus of Hsp70-interacting protein (CHIP) and provides a cochaperone-dependent regulatory mechanism for preventing unregulated ubiquitylation of misfolded proteins by CHIP (PMID:16169850)
• The activity of BAG-2 resembles that of the previously characterized Hsc70 cochaperone and CHIP inhibitor HspBP1. (PMID:16207813)
• we measured the binding of human Hsp72 (HSPA1A) to BAG1, BAG2, BAG3, and the unrelated NEF Hsp105. These studies revealed a clear hierarchy of affinities: BAG3 > BAG1 > Hsp105 » BAG2. (PMID:24318877)
• this data correlate BAG2 to PINK1 for the first time, strengthening the important role of BAG2 in Parkinson disease -related neurodegeneration. (PMID:24383081)
• This study showed that BAG2 (Bcl-2 associated athanogene family protein 2) and BAG5 (Bcl-2-associated athanogene family protein 5) stabilise pathogenic ataxin3-80Q by inhibiting its ubiquitination (PMID:25006867)
• NF-kappaB-mediated modulation of BAG2 expression regulates the shift between the neurotrophic and neurotoxic effects of Abeta1-42. (PMID:25985852)
• repression of BAG2 expression or BAG2 activity by cold-sensitive pathways, as modeled in undifferentiated and differentiated cells, respectively, may be a causal factor in the accumulation of cytotoxic hyperphosphorylated tau protein. (PMID:26208804)
• Thus, BAG2 promotes mutant p53 accumulation and gain-of-function in tumor growth, metastasis and chemoresistance. (PMID:26271008)
• Data show that BAG2 Inhibits CHIP-Mediated HSP72 ubiquitination in aged cells. (PMID:28042827)
• A comprehensive review of the structure, functions, and protein interactions of BAG2 (PMID:28536620)
• the nucleotide exchange factor (NEF) Bag2 stimulates SV40 release from Hsc70, thereby enabling successful virus arrival at the cytosol, which leads to infection. Hsp105, another NEF of Hsc70, displays a function overlapping that of Bag2, underscoring the importance of this release reaction. (PMID:29769335)
• High-regulated BAG2 is related to poor prognosis and could promote proliferation, invasion and migration of oral squamous cell carcinomas (PMID:31055249)
• LOXL1 confers antiapoptosis and promotes gliomagenesis through stabilizing BAG2. (PMID:32424143)
• Identification of BAG2 and Cathepsin D as Plasma Biomarkers for Parkinson’s Disease. (PMID:33202088)
• Bcl-2 Associated Athanogene 2 (BAG2) is Associated With Progression and Prognosis of Hepatocellular Carcinoma: A Bioinformatics-Based Analysis. (PMID:34257542)
• Helicobacter pylori Targets in AGS Human Gastric Adenocarcinoma: In Situ Proteomic Profiling and Systematic Analysis. (PMID:34969763)
• c-MYC-USP49-BAG2 axis promotes proliferation and chemoresistance of colorectal cancer cells in vitro. (PMID:35367823)
• BAG2 prevents Tau hyperphosphorylation and increases p62/SQSTM1 in cell models of neurodegeneration. (PMID:35612780)
• BAG2 drives chemoresistance of breast cancer by exacerbating mutant p53 aggregate. (PMID:36593950)
• Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma. (PMID:38236773)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bag2	ENSDARG00000035005
mus_musculus	Bag2	ENSMUSG00000042215
rattus_norvegicus	Bag2	ENSRNOG00000012709
drosophila_melanogaster	CG7945	FBGN0036505
caenorhabditis_elegans		WBGENE00006760

Protein

Protein identifiers

BAG family molecular chaperone regulator 2 — O95816 (reviewed: O95816)

Alternative names: Bcl-2-associated athanogene 2

All UniProt accessions (1): O95816

UniProt curated annotations — full annotation on UniProt →

Function. Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release.

Subunit / interactions. Binds to the ATPase domain of HSP/HSC70 chaperones. May interact with NWD1. Interacts with HSPA1A (via NBD), HSPA1B (via NBD) and HSPA8. May interact with DNJC9; the interaction seems to be histone-dependent.

Isoforms (2)

UniProt ID	Names	Canonical?
O95816-1	1	yes
O95816-2	2

RefSeq proteins (1): NP_004273* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003103	BAG_domain	Domain
IPR037689	BAG2	Family

UniProt features (10 total): modified residue 4, initiator methionine 1, chain 1, domain 1, coiled-coil region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95816-F1	86.55	0.67

Functional residue map

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

Post-translational modifications (4): 2, 20, 31, 73

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-9918487	Dengue Virus Genome Translation and Replication
R-HSA-2262752	Cellular responses to stress
R-HSA-3371556	Cellular response to heat stress
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 263 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, AP1_01, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_PROTEIN_MATURATION, AP1_Q4_01, ONKEN_UVEAL_MELANOMA_UP, chr6p12, GOBP_REGULATION_OF_CATABOLIC_PROCESS

GO Biological Process (7): protein folding (GO:0006457), positive regulation of protein processing (GO:0010954), protein metabolic process (GO:0019538), negative regulation of protein ubiquitination (GO:0031397), protein stabilization (GO:0050821), positive regulation of proteasomal protein catabolic process (GO:1901800), positive regulation of proteolysis (GO:0045862)

GO Molecular Function (8): adenyl-nucleotide exchange factor activity (GO:0000774), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), transmembrane transporter binding (GO:0044325), tau protein binding (GO:0048156), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (6): cytosol (GO:0005829), axon (GO:0030424), dendrite (GO:0030425), protein folding chaperone complex (GO:0101031), dendritic microtubule (GO:1901588), microtubule (GO:0005874)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cellular response to heat stress	1
Dengue Virus Infection	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
neuron projection	2
cellular process	1
protein maturation	1
protein processing	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
macromolecule metabolic process	1
primary metabolic process	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
regulation of protein stability	1
proteasomal protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
proteolysis	1
regulation of proteolysis	1
positive regulation of protein metabolic process	1
ATP binding	1
ADP binding	1
ATPase regulator activity	1
ubiquitin-like protein ligase binding	1
cytoskeletal protein binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1
dendritic tree	1
intracellular protein-containing complex	1
microtubule	1
dendrite	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

1442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BAG2	HSPA8	P11142	997
BAG2	HSPA4	P34932	990
BAG2	BAG1	Q99933	979
BAG2	STUB1	Q9UNE7	976
BAG2	HSPH1	Q92598	955
BAG2	BAG3	O95817	934
BAG2	SGTA	O43765	921
BAG2	BAG5	Q9UL15	903
BAG2	BAG4	O95429	853
BAG2	HSP90AA1	P07900	660
BAG2	HSP90AB1	P08238	659
BAG2	DNAJB1	P25685	638
BAG2	MT1A	P04731	635
BAG2	HSPA1A	P08107	619
BAG2	HSPBP1	Q9NZL4	599

IntAct

431 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
NPHP1	NPHP4	psi-mi:“MI:2364”(proximity)	0.930
HSPA8	BAG2	psi-mi:“MI:2364”(proximity)	0.860
BAG2	HSPA8	psi-mi:“MI:0915”(physical association)	0.860
BAG2	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.710
BAG2	BAG2	psi-mi:“MI:0915”(physical association)	0.680
BAG2	ATXN1	psi-mi:“MI:0915”(physical association)	0.670
PPP2R2B	MYO9A	psi-mi:“MI:0914”(association)	0.640
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
CPSF3	CPSF4	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
BAG2	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.590
PHLPP1	USP12	psi-mi:“MI:0914”(association)	0.570
BAG2	DISC1	psi-mi:“MI:0915”(physical association)	0.560
DAPK1	SVIL	psi-mi:“MI:0914”(association)	0.530
DAPK1	MYO1B	psi-mi:“MI:0914”(association)	0.530
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
IRAK1	SEC16A	psi-mi:“MI:0914”(association)	0.530
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
ARAF	BAG2	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530

BioGRID (1819): BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-Western), BAG2 (Two-hybrid), BAG2 (Reconstituted Complex), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1P8ARG1, A0A1S3X835, A6NKT7, B3LHE1, E7KNG0, E7NHN2, E7Q3U9, F4HVS6, F4HYG2, F4I131, F4IJK1, F4KEW8, O48767, O95816, P0DMS1, P21651, P46640, P48002, Q10006, Q12912, Q1T763, Q2T9U9, Q3UYG1, Q3ZBG5, Q56WM6, Q5XVI1, Q811D2, Q8LPQ1, Q8S8C6, Q91YN9, Q93ZY2, Q94CG5, Q94FL6, Q9BXU0, Q9C8Y4, Q9C9F5, Q9CR81, Q9FG14, Q9FX84, Q9LEZ4

Diamond homologs: O95816, Q3ZBG5, Q91YN9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAPKAPK2	up-regulates	BAG2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 221 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Degradation of DVL	6	9.3×	4e-03
Negative regulation of the PI3K/AKT network	5	9.1×	9e-03
Signaling by RAF1 mutants	5	9.1×	9e-03
Antimicrobial mechanism of IFN-stimulated genes	7	9.0×	2e-03
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	7	8.9×	2e-03
Interferon Signaling	10	7.9×	1e-04
Activation of NF-kappaB in B cells	6	7.7×	9e-03
PKR-mediated signaling	8	7.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
insulin-like growth factor receptor signaling pathway	6	15.9×	4e-04
obsolete positive regulation of NF-kappaB transcription factor activity	10	11.0×	1e-05
cellular response to growth factor stimulus	6	10.2×	4e-03
mitotic spindle organization	6	8.7×	8e-03
protein autophosphorylation	11	8.6×	2e-05
MAPK cascade	10	8.2×	1e-04
protein phosphorylation	18	6.5×	3e-07
mitotic cell cycle	9	6.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	29
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
145584	GRCh38/hg38 6p12.3-11.2(chr6:50971182-57432788)x1	Pathogenic
148002	GRCh38/hg38 6p12.1-q12(chr6:53931543-68149750)x3	Pathogenic
4279318	GRCh37/hg19 6p12.1-11.2(chr6:56988171-57193366)x1	Pathogenic

SpliceAI

439 predictions. Top by Δscore:

Variant	Effect	Δscore
6:57172809:AGG:A	donor_loss	1.0000
6:57172810:GGTGA:G	donor_loss	1.0000
6:57172811:GTGA:G	donor_loss	1.0000
6:57172811:G:GG	donor_gain	0.9900
6:57172812:T:G	donor_loss	0.9900
6:57182028:ATAG:A	acceptor_gain	0.9900
6:57182030:AG:A	acceptor_gain	0.9900
6:57182031:GG:G	acceptor_gain	0.9900
6:57182120:GACA:G	donor_gain	0.9900
6:57182139:ACGG:A	donor_loss	0.9900
6:57182140:CGGT:C	donor_loss	0.9900
6:57182141:GGTGA:G	donor_loss	0.9900
6:57182142:G:GG	donor_gain	0.9900
6:57182142:GTGAG:G	donor_loss	0.9900
6:57182143:T:C	donor_loss	0.9900
6:57182144:G:GG	donor_loss	0.9900
6:57182199:A:G	donor_gain	0.9900
6:57172809:AG:A	donor_gain	0.9800
6:57172810:GG:G	donor_gain	0.9800
6:57182103:G:GG	donor_gain	0.9800
6:57182128:GCAGA:G	donor_gain	0.9800
6:57182132:A:G	donor_gain	0.9800
6:57182102:A:AG	donor_gain	0.9700
6:57182203:GT:G	donor_gain	0.9700
6:57183915:GTCAA:G	donor_gain	0.9700
6:57183916:TCAAT:T	donor_gain	0.9700
6:57172807:TCAG:T	donor_gain	0.9600
6:57172808:CAG:C	donor_gain	0.9600
6:57182027:TATA:T	acceptor_loss	0.9600
6:57182029:TAGG:T	acceptor_loss	0.9600

AlphaMissense

1398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:57182047:A:C	R43S	1.000
6:57182047:A:T	R43S	1.000
6:57183804:G:C	A84P	1.000
6:57183814:T:C	L87S	1.000
6:57183835:T:A	V94D	1.000
6:57183892:C:A	A113D	1.000
6:57184018:T:C	F155S	1.000
6:57184038:T:C	C162R	1.000
6:57172792:T:C	L32P	0.999
6:57172803:G:A	E36K	0.999
6:57182046:G:C	R43T	0.999
6:57182046:G:T	R43I	0.999
6:57182054:G:C	A46P	0.999
6:57182055:C:A	A46E	0.999
6:57182085:T:C	L56P	0.999
6:57183793:T:C	L80S	0.999
6:57183799:T:C	L82P	0.999
6:57183811:G:C	R86P	0.999
6:57183814:T:G	L87W	0.999
6:57183823:G:C	R90T	0.999
6:57183824:A:C	R90S	0.999
6:57183824:A:T	R90S	0.999
6:57183859:G:C	R102T	0.999
6:57183859:G:T	R102I	0.999
6:57183860:A:C	R102S	0.999
6:57183860:A:T	R102S	0.999
6:57183883:T:C	L110P	0.999
6:57183891:G:C	A113P	0.999
6:57183978:T:C	C142R	0.999
6:57184017:T:C	F155L	0.999

dbSNP variants (sampled 300 via entrez): RS1000195032 (6:57171476 C>T), RS1000513353 (6:57175297 T>G), RS1000700013 (6:57171825 G>A), RS1000734649 (6:57176253 C>T), RS1000804002 (6:57178014 G>A), RS1000810921 (6:57189866 T>A), RS1000976181 (6:57173139 C>A,T), RS1001067163 (6:57173418 C>T), RS1001127673 (6:57184359 A>G), RS1001472693 (6:57177304 C>A), RS1001610313 (6:57176535 T>A), RS1001784571 (6:57176865 C>T), RS1001809280 (6:57184725 CTG>C), RS1001861979 (6:57175859 G>T), RS1002092256 (6:57182782 CT>C)

Disease associations

OMIM: gene MIM:603882 | disease phenotypes: MIM:119530, MIM:201000

GenCC curated gene-disease

Mondo (2): orofacial cleft (MONDO:0000358), RAB23-related Carpenter syndrome (MONDO:0008710)

Orphanet (1): Carpenter syndrome (Orphanet:65759)

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: yes

ChEMBL targets (1): CHEMBL5725021 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.75	Kd	17.66	nM	CHEMBL3752910
7.73	ED50	18.78	nM	CHEMBL3752910
7.24	Kd	58	nM	MOLIBRESIB
6.92	IC50	120	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 9 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149832: Binding affinity to human BAG2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0177	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179218: Binding affinity against BAG2 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0580	uM

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
methylmercuric chloride	increases expression, affects cotreatment	4
bisphenol A	decreases expression, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases expression, affects methylation, affects cotreatment, increases abundance	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Estradiol	increases expression, increases reaction	2
Hydrogen Peroxide	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
pinosylvin	decreases expression	1
polyhexamethyleneguanidine	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652874	Binding	Binding affinity to human BAG2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1KX	Abcam HeLa BAG2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04342234	Not specified	RECRUITING	Neural Network to Calculate Morphology of the Cleft Palate to Reduce Cleft Lip and Palate Treatment Burden.
NCT05867862	Not specified	COMPLETED	Implementation of a Program to Strengthen Oral Hygiene in Patient With Cleft Deformities
NCT06880094	Not specified	RECRUITING	Study of Congenital Orofacial Clefts by Implementing Optical Genome Mapping
NCT07340008	Not specified	RECRUITING	Analgosedation With Ketamine, Nalbuphine, or Dexmedetomidine for Suture Removal in Children After Cleft Surgery
NCT07557576	Not specified	RECRUITING	Effect of Opioid-Free vs Opioid-Based Anesthesia on Postoperative Pain and Emergence Agitation in Children Undergoing Cleft Surgery