BAG1

Summary

BAG1 (BAG cochaperone 1, HGNC:937) is a protein-coding gene on chromosome 9p13.3, encoding BAG family molecular chaperone regulator 1 (Q99933). Co-chaperone for HSP70 and HSC70 chaperone proteins.

The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein encoded by this gene binds to BCL2 and is referred to as BCL2-associated athanogene. It enhances the anti-apoptotic effects of BCL2 and represents a link between growth factor receptors and anti-apoptotic mechanisms. Multiple protein isoforms are encoded by this mRNA through the use of a non-AUG (CUG) initiation codon, and three alternative downstream AUG initiation codons. A related pseudogene has been defined on chromosome X.

Source: NCBI Gene 573 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 57 total — 1 likely-pathogenic
• MANE Select transcript: NM_004323

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:937
Approved symbol	BAG1
Name	BAG cochaperone 1
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000107262
Ensembl biotype	protein_coding
OMIM	601497
Entrez	573

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000379701, ENST00000379704, ENST00000379707, ENST00000467389, ENST00000468274, ENST00000473464, ENST00000473781, ENST00000488499, ENST00000493917, ENST00000634734, ENST00000635077

RefSeq mRNA: 4 — MANE Select: NM_004323 NM_001172415, NM_001349286, NM_001349299, NM_004323

CCDS: CCDS35004, CCDS55301

Canonical transcript exons

ENST00000634734 — 7 exons

Exon	Start	End
ENSE00002346915	33262702	33262830
ENSE00003506454	33255865	33255927
ENSE00003569638	33256801	33256908
ENSE00003574940	33261087	33261169
ENSE00003684099	33258920	33259033
ENSE00003785100	33252471	33255308
ENSE00003847903	33264224	33264708

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.7412 / max 2184.4459, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100448	51.2611	1827
100447	2.4801	1109

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.29	gold quality
sperm	CL:0000019	98.74	gold quality
male germ cell	CL:0000015	98.50	gold quality
apex of heart	UBERON:0002098	98.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.47	gold quality
right atrium auricular region	UBERON:0006631	98.44	gold quality
right testis	UBERON:0004534	98.39	gold quality
left testis	UBERON:0004533	98.27	gold quality
skin of abdomen	UBERON:0001416	98.19	gold quality
gastrocnemius	UBERON:0001388	98.14	gold quality
skin of leg	UBERON:0001511	98.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.85	gold quality
lower esophagus	UBERON:0013473	97.84	gold quality
muscle of leg	UBERON:0001383	97.74	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.56	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.47	gold quality
metanephros cortex	UBERON:0010533	97.45	gold quality
rectum	UBERON:0001052	97.39	gold quality
body of stomach	UBERON:0001161	97.39	gold quality
tendon of biceps brachii	UBERON:0008188	97.39	gold quality
blood	UBERON:0000178	97.27	gold quality
minor salivary gland	UBERON:0001830	97.26	gold quality
adenohypophysis	UBERON:0002196	97.24	gold quality
esophagus	UBERON:0001043	97.11	gold quality
mucosa of stomach	UBERON:0001199	97.11	gold quality
monocyte	CL:0000576	97.06	gold quality
nucleus accumbens	UBERON:0001882	97.04	gold quality
gluteal muscle	UBERON:0002000	97.01	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	119.54
E-GEOD-134144	yes	31.70
E-HCAD-1	yes	13.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCFL, DNMT1, DNMT3B, NFKB1, NFKB, SOX9, TP53, TP73

miRNA regulators (miRDB)

87 targeting BAG1, 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-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-10393-5P	99.65	68.01	1368

Literature-anchored findings (GeneRIF, showing 40)

• BAG-1, an anti-apoptotic tumour marker Review (PMID:12049201)
• nuclear BAG-1 expression is a useful predictive factor for distant metastasis and a poor prognosis in patients with colorectal cancer. (PMID:12402153)
• BAG-1 may function to suppress the GADD34-mediated cellular stress response and have a role in the survival of cells undergoing stress (PMID:12724406)
• BAG-1-mediated resistance to stress-induced growth inhibition is likely to have a major impact on the development and response to therapy of breast cancer. (PMID:12874020)
• Bag-1L enhances androgen receptor action via interaction with the NH2-terminal region of the receptor (PMID:14517289)
• BAG-1 is targeted to the COPI coated structures, implying its contribution toward the COPI vesicular transport in gastrointestinal epithelial cells (PMID:14532969)
• Our experiments suggest that BAG-1 inhibits anti-cancer drug-induced apoptosis through apoptosis regulation pathways that may involve the mitochondrial Bcl-2/Bax ratio, p53, and differential anti-cancer drug-mediated cytochrome c release. (PMID:14680805)
• Recombinant BAG-1 can influence cellular response to stress in cardiomyocytes by multiple mechanisms, potentially influenced by the cell type and nature of the stress signal. (PMID:14978028)
• P. 130:…"[h]igh expression of Bcl-2", was one of the predictive factors “for achievement of pathological remission after preoperative chemotherapy” containing anthracycline. (PMID:15075668)
• a secondary structural model of the Bag-1 IRES has been derived by using chemical and enzymatic probing data as constraints on the RNA folding algorithm Mfold (PMID:15169918)
• BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues, but does not appear to determine response to doxorubicin-based chemotherapy (PMID:15199607)
• BAG-1 is expressed in the endometrium. High-grade cancers stain more frequently than secretory endometrium for both cytoplasmic and nuclear BAG-1 expression, perhaps indicating an association between expression of BAG-1 and prognosis. (PMID:15297164)
• The results of this study implicate BAG-1 p29 in the regulation of both the EGF signaling cascade and the apoptotic cascade induced by loss of anchorage. (PMID:15707960)
• BAG1 activates Hsp70, which is important for neuroprotectivity. (PMID:15831476)
• BAG-1 expression inhibits apoptosis in colorectal adenoma-derived epithelial cells (PMID:15843891)
• BAG-1 may promote colorectal tumour cell survival by making colonic epithelial cells less sensitive to DNA damage. (PMID:16042572)
• In astrocytic tumours low ERbeta expression correlated significantly with high grade, higher expression of cytoplasmic BAG-1 and worse survival. (PMID:16292491)
• Overexpression of BAG-1 and p53 plays an important role in the process laryngeal squamous cell carcinoma development. (PMID:16398049)
• BAG-1 protein showed distinct distribution pattern in hyperplastic and neoplastic prostate. BAG-1 with BCL-2 inhibits apoptosis and may prolong the life of neoplastic cells and give them a chance to gain new oncogenic features in early carcinogenesis. (PMID:16457154)
• Increased cytosolic and nuclear BAG-1 expression may denote more aggressive variants of prostate cancer. (PMID:16482527)
• This is the molecular basis for their effects (Hap50/BAG-1L) on transcriptional activities, which are emphasized in this review and for which a molecular model is presented. (PMID:17278878)
• An antiapoptotic protein, BAG-1, was found to be down-regulated in chewing-tobacco-mediated tongue carcinogenesis. (PMID:17549665)
• over-expression of BAG1 may play an important role in genesis and development of colon carcinoma (PMID:17657847)
• BAG-1L endogenously regulates gene expression by potentiating nuclear hormone receptor function and a role for BAG-1L in 24-hydroxylase regulation of vitamin D metabolism and the cellular response of oral keratinocytes to 1alpha,25-dihydroxyvitamin D3. (PMID:17662274)
• Results suggest that BAG-1 is able to potentiate vitamin D receptor-mediated transactivation by acting as a nuclear chaperone for 1,25(OH)2D3. (PMID:17693608)
• BAG-1 mRNA internal ribosome entry segment maintains synthesis of BAG-1 protein following exposure of cells to the chemotoxic drug vincristine but not to cisplatin. (PMID:17700523)
• Modulation of Bag-1 expression can therefore mediate chondrocyte differentiation and turnover (PMID:17950682)
• BAG-1 associates with Tau protein in an Hsc70-dependent manner. (PMID:17954934)
• By inhibiting NF-kappaB, suppression of BAG-1 could represent a novel strategy to impede colorectal cancer cell survival and as an adjuvant increase sensitivity to current therapeutic regimes. (PMID:18204076)
• Chromatin immunoprecipitation analysis of the BAG-1 promoter in DNMT1-overexpressing or DNMT3B-overexpressing colon cells show a permissive chromatin status assoscsiated with DNA binding of BORIS. (PMID:18413740)
• Bag-1 expression in breast tumors is associated with improved outcome and steroid receptor positivity. (PMID:18430249)
• BAG-1 protein was deregulated in this disease similar to some other malignancies such as breast and colon cancer (PMID:18523358)
• Bag1 NEF increased refolding by Hsc70 and DJA2, as did the newly characterized NEF Hsp110 (PMID:18684711)
• Gene expression revealed up-regulation of pro-angiogenic (PGF), anti-apoptotics (BAG-1, BCL-2), heart development (TNNT2, TNNC1) and extracellular matrix remodelling (MMP-2, MMP-7) genes in SM. (PMID:18805052)
• These findings identify a regulatory mechanism, downstream of hormone binding, used by Bag-1M for attenuating GR action in response to its changing cellular levels. (PMID:18822299)
• A high BAG-1 expression predicts improved patient outcome in estrogen receptor-positive breast carcinoma. (PMID:19066611)
• Distinct isoforms of BAG-1 have different anti-apoptotic functions in breast cancer cells, and that the BAG-1 p50 isoform can potentiate the role of estrogen in ER-positive breast cancer. (PMID:19151744)
• The results of our study showed that overall cytoplasmic and nuclear BAG-1 expression and overall and cytoplasmic CD24 expression, correlates with adverse prognostic parameters for breast carcinoma. (PMID:19243896)
• BAG-1 inhibits the transactivating functions of p73 and provide new insight into the mechanisms that control the expression of p73. (PMID:19293798)
• we report a specific increase of BAG-1M in human Alzheimer’s disease patients (PMID:19317853)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bag1	ENSDARG00000020895
mus_musculus	Bag1	ENSMUSG00000028416
rattus_norvegicus	Bag1	ENSRNOG00000008277
caenorhabditis_elegans	bag-1	WBGENE00000236

Protein

Protein identifiers

BAG family molecular chaperone regulator 1 — Q99933 (reviewed: Q99933)

Alternative names: Bcl-2-associated athanogene 1

All UniProt accessions (6): Q99933, A0A0U1RR89, C9J9Y9, C9JYK5, F1LLU6, J3QTA2

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. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli. Involved in the STUB1-mediated proteasomal degradation of ESR1 in response to age-related circulating estradiol (17-beta-estradiol/E2) decline, thereby promotes neuronal apoptosis in response to ischemic reperfusion injury.

Subunit / interactions. Homodimer. Forms a heteromeric complex with HSP70/HSC70. Binds to the ATPase domain of HSP/HSC70 chaperones. Isoform 1, isoform 3 and isoform 4 but not isoform 2 interact with HSPA8/HSC70. Interacts with NR3C1. Interacts with the N-terminal region of MAPRE2. Interacts with PPP1R15A. Interacts with BCL2 in an ATP-dependent manner. Isoform 2 does not interact with BCL2. Interacts with SIAH1. Interacts with HSPA8 (via NBD). Interacts with HSPA1A (via NBD) and HSPA1B (via NBD). Interacts with SIAH2. Interacts with ESR1; the interaction is promoted in the absence of estradiol (17-beta-estradiol/E2).

Subcellular location. Nucleus. Cytoplasm Cytoplasm. Nucleus Cytoplasm.

Tissue specificity. Isoform 4 is the most abundantly expressed isoform. It is ubiquitously expressed throughout most tissues, except the liver, colon, breast and uterine myometrium. Isoform 1 is expressed in the ovary and testis. Isoform 4 is expressed in several types of tumor cell lines, and at consistently high levels in leukemia and lymphoma cell lines. Isoform 1 is expressed in the prostate, breast and leukemia cell lines. Isoform 3 is the least abundant isoform in tumor cell lines (at protein level).

Post-translational modifications. Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation.

Induction. Up-regulated during differentiation of bladder epithelial cells and down-regulated during differentiation of prostate epithelium.

Miscellaneous. Produced by alternative splicing. Produced by alternative initiation at Met-72 of isoform 1. Produced by alternative initiation at Met-116 of isoform 1.

Isoforms (4)

UniProt ID	Names	Canonical?
Q99933-1	1, BAG-1L, p50	yes
Q99933-2	2, BAG1V, HAPV
Q99933-3	3, BAG-1M, RAP46
Q99933-4	4, BAG-1, p32

RefSeq proteins (4): NP_001165886, NP_001336215, NP_001336228, NP_004314* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR003103	BAG_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036533	BAG_dom_sf	Homologous_superfamily
IPR039773	BAG_chaperone_regulator	Family

Pfam: PF00240, PF02179

UniProt features (44 total): strand 8, repeat 7, sequence conflict 6, helix 6, region of interest 4, compositionally biased region 4, splice variant 3, domain 2, chain 1, modified residue 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
5AQM	X-RAY DIFFRACTION	1.63
5AQL	X-RAY DIFFRACTION	1.69
5AQV	X-RAY DIFFRACTION	1.75
5AQF	X-RAY DIFFRACTION	1.88
1HX1	X-RAY DIFFRACTION	1.9
3LDQ	X-RAY DIFFRACTION	1.9
5AQT	X-RAY DIFFRACTION	1.9
5AQR	X-RAY DIFFRACTION	1.91
5AQU	X-RAY DIFFRACTION	1.92
5AQJ	X-RAY DIFFRACTION	1.96
5AQI	X-RAY DIFFRACTION	1.98
3FZH	X-RAY DIFFRACTION	2
5AQH	X-RAY DIFFRACTION	2
5AQS	X-RAY DIFFRACTION	2
5AQP	X-RAY DIFFRACTION	2.08
5AQK	X-RAY DIFFRACTION	2.09
3FZK	X-RAY DIFFRACTION	2.1
3M3Z	X-RAY DIFFRACTION	2.1
5AQO	X-RAY DIFFRACTION	2.12
3FZF	X-RAY DIFFRACTION	2.2
3FZL	X-RAY DIFFRACTION	2.2
5AQG	X-RAY DIFFRACTION	2.24
3FZM	X-RAY DIFFRACTION	2.3
5AQN	X-RAY DIFFRACTION	2.45
5AQQ	X-RAY DIFFRACTION	2.72
9SZT	ELECTRON MICROSCOPY	3.5
9HEU	ELECTRON MICROSCOPY	3.6
9SZV	ELECTRON MICROSCOPY	3.6
1WXV	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99933-F1	62.89	0.06

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 (1): 223

Mutagenesis-validated functional residues (1):

Position	Phenotype
308–309	significant loss of interaction with hspa8.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
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: 182 (showing top): TGCGCANK_UNKNOWN, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GGGTGGRR_PAX4_03, WEINMANN_ADAPTATION_TO_HYPOXIA_UP, GOBP_PROTEIN_MATURATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_PROTEIN_STABILIZATION, chr9p13, DER_IFN_BETA_RESPONSE_UP, AIYAR_COBRA1_TARGETS_DN, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, GOBP_PROTEIN_FOLDING, GOBP_REGULATION_OF_PROTEIN_STABILITY

GO Biological Process (6): protein folding (GO:0006457), apoptotic process (GO:0006915), cell surface receptor signaling pathway (GO:0007166), positive regulation of smooth muscle cell apoptotic process (GO:0034393), negative regulation of apoptotic process (GO:0043066), protein stabilization (GO:0050821)

GO Molecular Function (4): adenyl-nucleotide exchange factor activity (GO:0000774), ubiquitin protein ligase binding (GO:0031625), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular response to heat stress	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	1
protein maturation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
signal transduction	1
positive regulation of muscle cell apoptotic process	1
smooth muscle cell apoptotic process	1
regulation of smooth muscle cell apoptotic process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of protein stability	1
ATP binding	1
ADP binding	1
ATPase regulator activity	1
ubiquitin-like protein ligase binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1261 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BAG1	HSPA8	P11142	998
BAG1	HSPA4	P34932	997
BAG1	BCL2	P10415	993
BAG1	DNAJB1	P25685	988
BAG1	BAG2	O95816	979
BAG1	BAG3	O95817	935
BAG1	HSP90AA1	P07900	878
BAG1	HSP90AB1	P08238	876
BAG1	RAF1	P04049	876
BAG1	BAG5	Q9UL15	867
BAG1	BAG4	O95429	841
BAG1	ST13	P50502	823
BAG1	HSPA1A	P08107	789
BAG1	STUB1	Q9UNE7	785
BAG1	STIP1	P31948	764

IntAct

109 interactions, top by confidence:

A	B	Type	Score
BAG1	PSMD2	psi-mi:“MI:0915”(physical association)	0.830
PSMD2	BAG1	psi-mi:“MI:0915”(physical association)	0.830
BAG1	HSPA8	psi-mi:“MI:0915”(physical association)	0.790
HSPA8	BAG1	psi-mi:“MI:0915”(physical association)	0.790
BAG1	HSPA8	psi-mi:“MI:0407”(direct interaction)	0.790
HSPA8	BAG1	psi-mi:“MI:0407”(direct interaction)	0.790
BAG1	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	BAG1	psi-mi:“MI:0915”(physical association)	0.780
TRIM23	BAG1	psi-mi:“MI:0915”(physical association)	0.700

BioGRID (595): BAG1 (Two-hybrid), HSPA8 (Two-hybrid), PSMD2 (Two-hybrid), TRIM27 (Two-hybrid), BAG1 (Reconstituted Complex), BAG1 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), BAG1 (Co-fractionation), BAG1 (Co-fractionation), BAG1 (Co-fractionation), BAG1 (Co-fractionation)

ESM2 similar proteins: A1L1K1, A2ARM1, A2AVJ5, A4IFC9, A7E305, G5EGQ2, O08653, O36006, O43435, O46080, O95343, P13481, P28702, P28704, P56423, P56424, P56645, P61260, P97499, Q02556, Q07820, Q2NL16, Q32N92, Q5E9R0, Q5REG4, Q5SQI0, Q5TJF7, Q5U2W6, Q5U2Y1, Q61010, Q62233, Q6MZQ0, Q80V91, Q86Y01, Q86YD1, Q8AW93, Q8BIG4, Q8HYS5, Q8N9I9, Q91VU8

Diamond homologs: B0K019, Q60739, Q99933, O44739, Q61D31

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
DNMT1	“up-regulates quantity by expression”	BAG1	“transcriptional regulation”
DNMT3B	“up-regulates quantity by expression”	BAG1	“transcriptional regulation”
BAG1	“down-regulates activity”	PPP1R15A
BAG1	“up-regulates activity”	BCL2	binding
CTCFL	“up-regulates quantity by expression”	BAG1	“transcriptional regulation”
BAG1	“up-regulates activity”	HSPA8	binding
BAG1	“up-regulates activity”	STUB1	binding
BAG1	“down-regulates quantity by destabilization”	HSPA8	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
AUF1 (hnRNP D0) binds and destabilizes mRNA	6	29.8×	2e-05
Autodegradation of the E3 ubiquitin ligase COP1	5	26.6×	1e-04
Regulation of PTEN stability and activity	6	22.1×	6e-05
Proteasome assembly	5	20.4×	4e-04
Regulation of HSF1-mediated heat shock response	7	19.5×	2e-05
The role of GTSE1 in G2/M progression after G2 checkpoint	6	19.3×	9e-05
Regulation of RUNX2 expression and activity	5	18.1×	5e-04
Hedgehog ‘on’ state	5	15.9×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of protein ubiquitination	6	17.3×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	45
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
559575	GRCh37/hg19 9p24.3-11.2(chr9:204193-44259464)x4	Likely pathogenic

SpliceAI

936 predictions. Top by Δscore:

Variant	Effect	Δscore
9:33255306:TGC:T	acceptor_gain	1.0000
9:33255306:TGCC:T	acceptor_loss	1.0000
9:33255308:CCTAG:C	acceptor_loss	1.0000
9:33255309:CTA:C	acceptor_loss	1.0000
9:33255925:GATC:G	acceptor_loss	1.0000
9:33255927:TC:T	acceptor_loss	1.0000
9:33255928:C:T	acceptor_loss	1.0000
9:33255929:T:G	acceptor_loss	1.0000
9:33255930:A:C	acceptor_gain	1.0000
9:33256798:TA:T	donor_loss	1.0000
9:33256799:A:AC	donor_gain	1.0000
9:33256799:AC:A	donor_gain	1.0000
9:33256800:C:CC	donor_gain	1.0000
9:33256800:CC:C	donor_gain	1.0000
9:33256800:CCA:C	donor_gain	1.0000
9:33256800:CCAG:C	donor_gain	1.0000
9:33256800:CCAGT:C	donor_gain	1.0000
9:33256904:AAACC:A	acceptor_gain	1.0000
9:33256905:AACC:A	acceptor_gain	1.0000
9:33256906:ACC:A	acceptor_gain	1.0000
9:33256907:CC:C	acceptor_gain	1.0000
9:33256907:CCC:C	acceptor_gain	1.0000
9:33256908:CC:C	acceptor_gain	1.0000
9:33256909:C:CA	acceptor_loss	1.0000
9:33256909:C:CC	acceptor_gain	1.0000
9:33256910:T:A	acceptor_loss	1.0000
9:33258915:GTTAC:G	donor_loss	1.0000
9:33258916:TTACC:T	donor_loss	1.0000
9:33258917:TA:T	donor_loss	1.0000
9:33258919:CCTG:C	donor_gain	1.0000

AlphaMissense

2245 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:33262710:A:T	I191K	0.997
9:33262710:A:G	I191T	0.995
9:33264232:A:T	V148D	0.995
9:33261106:A:T	V215D	0.994
9:33262734:A:T	V183D	0.994
9:33261100:A:G	L217S	0.993
9:33262773:A:T	V170D	0.993
9:33261094:C:T	G219E	0.992
9:33261103:A:G	M216T	0.992
9:33262718:C:A	Q188H	0.992
9:33262718:C:G	Q188H	0.992
9:33262752:A:T	V177D	0.992
9:33255889:C:A	R308S	0.991
9:33255889:C:G	R308S	0.991
9:33261139:A:G	L204S	0.991
9:33261124:A:G	I209T	0.990
9:33262713:A:G	L190P	0.990
9:33261169:C:T	G194E	0.989
9:33262710:A:C	I191R	0.989
9:33262713:A:T	L190H	0.989
9:33261124:A:T	I209K	0.988
9:33261160:A:G	L197P	0.988
9:33262702:C:G	G194R	0.988
9:33262702:C:T	G194R	0.988
9:33262706:A:C	F192L	0.988
9:33262706:A:T	F192L	0.988
9:33262708:A:G	F192L	0.988
9:33256903:A:C	F261L	0.986
9:33256903:A:T	F261L	0.986
9:33256905:A:G	F261L	0.986

dbSNP variants (sampled 300 via entrez): RS1000234535 (9:33263396 C>A,G), RS1000774456 (9:33257209 G>A), RS1000982073 (9:33264981 G>A), RS1001269373 (9:33253698 G>T), RS1001287597 (9:33264657 C>A,G,T), RS1001553115 (9:33258761 G>A), RS1001596770 (9:33262370 C>T), RS1001647674 (9:33262667 A>G), RS1001935346 (9:33263713 G>A), RS1001987740 (9:33263972 G>T), RS1002166562 (9:33255372 G>A,C,T), RS1002276427 (9:33252427 G>A), RS1002524914 (9:33258422 C>A,T), RS1002607897 (9:33260671 A>G), RS1002718751 (9:33261835 G>T)

Disease associations

OMIM: gene MIM:601497 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010796_5113	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	7
cobaltous chloride	increases expression, increases reaction, decreases expression	4
Cadmium Chloride	decreases expression, increases expression, affects cotreatment	3
alvocidib	decreases expression	2
Air Pollutants	affects expression, affects cotreatment, decreases expression, increases abundance	2
Formaldehyde	decreases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Valproic Acid	affects expression, affects cotreatment, increases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
lead acetate	affects cotreatment, decreases expression	1
arsenite	increases expression, affects reaction	1
sulforaphane	decreases expression	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
zinc chromate	increases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric chloride	decreases expression	1
hydroquinone	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
7-hydroxystaurosporine	decreases expression	1
polyhexamethyleneguanidine	increases expression	1
usnic acid	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
candoxin	decreases expression	1
3,4,5,4’-tetramethoxystilbene	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	increases expression	1

Clinical trials (associated diseases)

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