BTG2

Summary

BTG2 (BTG anti-proliferation factor 2, HGNC:1131) is a protein-coding gene on chromosome 1q32.1, encoding Protein BTG2 (P78543). Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex.

The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein is involved in the regulation of the G1/S transition of the cell cycle.

Source: NCBI Gene 7832 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 28 total
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• MANE Select transcript: NM_006763

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1131
Approved symbol	BTG2
Name	BTG anti-proliferation factor 2
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	PC3, TIS21, MGC126063, MGC126064, APRO1
Ensembl gene	ENSG00000159388
Ensembl biotype	protein_coding
OMIM	601597
Entrez	7832

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000290551, ENST00000475157

RefSeq mRNA: 1 — MANE Select: NM_006763 NM_006763

CCDS: CCDS1437

Canonical transcript exons

ENST00000290551 — 2 exons

Exon	Start	End
ENSE00003992647	203307104	203309602
ENSE00003992651	203305519	203305748

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 184.4228 / max 11023.7574, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7876	184.4228	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.82	gold quality
cardia of stomach	UBERON:0001162	99.25	gold quality
body of pancreas	UBERON:0001150	99.10	gold quality
trachea	UBERON:0003126	99.00	gold quality
renal medulla	UBERON:0000362	98.94	gold quality
gall bladder	UBERON:0002110	98.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.72	gold quality
left uterine tube	UBERON:0001303	98.68	gold quality
periodontal ligament	UBERON:0008266	98.59	gold quality
pylorus	UBERON:0001166	98.56	gold quality
mucosa of urinary bladder	UBERON:0001259	98.55	gold quality
nipple	UBERON:0002030	98.53	gold quality
saphenous vein	UBERON:0007318	98.53	gold quality
popliteal artery	UBERON:0002250	98.51	gold quality
thymus	UBERON:0002370	98.51	gold quality
tibial artery	UBERON:0007610	98.51	gold quality
left ovary	UBERON:0002119	98.44	gold quality
monocyte	CL:0000576	98.38	gold quality
diaphragm	UBERON:0001103	98.36	gold quality
bone marrow cell	CL:0002092	98.33	gold quality
right atrium auricular region	UBERON:0006631	98.28	gold quality
mononuclear cell	CL:0000842	98.26	gold quality
cardiac atrium	UBERON:0002081	98.26	gold quality
right ovary	UBERON:0002118	98.23	gold quality
leukocyte	CL:0000738	98.20	gold quality
rectum	UBERON:0001052	98.13	gold quality
colonic epithelium	UBERON:0000397	97.94	gold quality
vermiform appendix	UBERON:0001154	97.94	gold quality
omental fat pad	UBERON:0010414	97.90	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	1143.40
E-HCAD-31	yes	808.48
E-CURD-122	yes	62.67
E-HCAD-6	yes	42.52
E-CURD-46	yes	40.28
E-HCAD-1	yes	40.26
E-MTAB-8410	yes	39.72
E-MTAB-10287	yes	31.92
E-CURD-119	yes	24.12
E-HCAD-10	yes	24.11
E-MTAB-6701	yes	16.71
E-GEOD-81608	yes	9.56
E-GEOD-125970	yes	9.10
E-GEOD-93593	yes	7.18
E-GEOD-137537	yes	6.11

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CAT	Activation
CCND1	Repression
HRAS	Repression
KLK3	Repression
SOD1	Activation
SOD2	Activation
SPHK1	Activation

Upstream regulators (CollecTRI, top): AR, ASCL1, CEBPB, CREB1, ESR1, ESR2, FOXM1, GATA1, HIF1A, NEUROG2, NFKB1, PHB2, RARA, RELA, RXRA, TP53

miRNA regulators (miRDB)

246 targeting BTG2, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 40)

• First evidence showing that PC3 / BTG2 acts as cell cycle checkpoint at G1 phase by inhibiting the expression of cyclin D1 (PMID:10669755)
• This review describes BTG2 / PC3 as link between p53 and pRb. p53 via BTG2 / PC3 may activate pRb, since the BTG2 / PC3 product promotes accumulation of hypophosphorylated pRb by reducing cyclin D1 protein levels and thereby inhibiting CDK4 activity. (PMID:11267995)
• Transient expression assays with BTG2/TIS21/PC3 promoter deletions and electrophoretic mobility shift analysis identified a major wild-type p53 response element located -74 to -122 relative to the start codon. (PMID:11814693)
• Antiproliferative proteins of the BTG/Tob family are degraded by the ubiquitin-proteasome system. the C-terminal regions are necessary and sufficient to control the stabilities of BTG1, BTG2, Tob, and Tob2 proteins. (PMID:12135500)
• BTG2 interacts with the CCR4 complex and has a role in cell-cycle regulation (PMID:12771185)
• PC3 / BTG2 induces neural precursors to shift from proliferation to differentiation. This differentiative action occurs in cerebellar progenitors by a dual mechanism: inhibition of cell cycle (of cyclin D1) and induction of the proneural gene Math1. (PMID:15056715)
• deregulation of BTG2 may be an important step in the development of mammary tumors (PMID:15378000)
• DeltaNp73alpha not only acts as an inhibitor of p53/TAp73 functions in neuroblastoma tumors, but also cooperates with wt-p53 in playing a physiological role through the activation of BTG2TIS21/PC3 gene expression (PMID:15741235)
• binding of tis21/BTG2/pc3 to Pin-1 or cyclin B1-Cdc2 complex and induction of mitochondrial depolarization are responsible for the antiproliferative effects of EGF in human tumor cells (PMID:15788397)
• BTG2 expression was found to be significantly reduced in a large proportion of human kidney and breast carcinomas, suggesting that BTG2 is a tumor suppressor that links p53 and Rb pathways in human tumorigenesis. (PMID:16418486)
• BTG2 contributes to retinoic acid activity by favoring differentiation through a gene-specific modification of histone H4 arginine methylation and acetylation levels. (PMID:16782888)
• Reverse-transcription polymerase chain reaction confirmed increased expression of GADD45A, BTG2, PDE4B, and CEBPD and downregulation of TOB1 in skeletal muscle intradialysis. (PMID:16997058)
• PC3 / BTG2 acts as a tumor suppressor of medulloblastoma by its antiproliferative and prodifferentiative effect on cerebellar progenitors. This antagonizes Shh and appears physiologic since endogenous PC3 / BTG2 decreases in human medulloblastomas. (PMID:17371797)
• T3 upregulates proliferation of LNCaP cells by downregulating BTG2 gene expression through the consensus TRE pathway. (PMID:18196550)
• BTG2 expression may play a role at a very early point during the differentiation processes of hematopoietic cells. (PMID:18288394)
• BTG2 is a general activator of mRNA decay, thereby contributing to gene expression control. (PMID:18337750)
• TIS21 negatively regulated hepatocarcinogenesis in part by disruption of the FoxM1-cyclin B1 regulatory loop, thereby inhibiting proliferation of transformed cells developed in mouse and human livers. (PMID:18393292)
• BTG2/TIS21/PC3 enhances cancer cell death by accumulating H2O2 via imbalance of the antioxidant enzymes in response to chemotherapy. (PMID:18840609)
• Crystal structure of human BTG2 reveal the putative CAF1 binding site. (PMID:18974182)
• Estradiol downregulation of the tumor suppressor gene BTG2 requires estrogen receptor-alpha and the REA corepressor (PMID:19117054)
• miR-18 may negatively regulate the expression of BTG2 in HepG2 cells. (PMID:19203451)
• BTG2 may be a modulator of neuron survival and differentiation (PMID:19468252)
• Deregulation of BTG2, which was identified to be a miR-21 target gene, may be responsible for the miR-21-mediated abnormal cellular phenotype. (PMID:19546886)
• These data indicate that TIS21 is a novel target of SCF-Skp2 ubiquitin ligase, which is regulated by expression of FoxM1. (PMID:19615363)
• The influence of BTG2 on the growth, proliferation, apoptosis, invasion and cell cycle of the gastric cancer cell lines, was investigated. (PMID:19728149)
• Study of murine BTG2 suggests that BTG2 is essential for terminal differentiation of neural progenitors. Genetic ablation of BTG2 in rodents impairs terminal differentiation and shortens G1 phase of cell cycle duration of neural progenitor cells. (PMID:20020054)
• High-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma. (PMID:20553615)
• The neutralization of Pin1 by BTG2 provides a critical mechanism to maintain senescent arrest in the presence of mitogenic signals in normal primary fibroblasts. (PMID:20569234)
• Estrogen receptor beta causes a G2 cell cycle arrest by inactivating CDK1 through the repression of cyclin B1 and stimulation of GADD45A and BTG2 expression. (PMID:21120602)
• These findings, for the first time, demonstrate that BTG2 complexes with AR via an LxxLL-dependent mechanism and may play a role in prostate cancer via modulating the AR signaling pathway. (PMID:21172304)
• MIR32 is upregulated in prostate cancer and regulates expression of BTG2. (PMID:22266859)
• Results suggest that the overexpression of B cell translocation gene 2 (BTG2) may inhibit the growth, proliferation, and invasiveness of the A549 lung cancer cell line. (PMID:22392501)
• a novel role for BTG2 as a co-activator for NFE2L2 in up-regulating cellular antioxidant defenses. (PMID:22493435)
• study reveals that BTG2 negatively regulated cancer cell migration by inhibiting Src activity through downregulation of reactive oxygen species generation in mitochondria (PMID:22562501)
• Downregulation of the basal protein B-cell translocation gene 2 is associated with prostate cancer transformation and progression. (PMID:22614007)
• TIS21 regulates DNA double strand break repair and apoptosis via increasing Mre11 methylation. (PMID:23089312)
• These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. (PMID:23299537)
• Data indicate that the pattern of B cell translocation gene 2 (BTG2) protein expression was exactly the opposite of miRNA-21 expression in lung cancer cells. (PMID:23857284)
• Reactive oxygen spieces regulate Btg2/TIS21/PC3 expression via Protein kinase C-NFkappaappaB pathway. (PMID:23876794)
• TIS21 suppresses invadopodia formation as well as invasion activity along with F-actin remodeling. (PMID:23907596)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	btg2	ENSDARG00000020298
mus_musculus	Btg2	ENSMUSG00000020423
rattus_norvegicus	Btg2	ENSRNOG00000003300

Paralogs (3): BTG1 (ENSG00000133639), BTG4 (ENSG00000137707), BTG3 (ENSG00000154640)

Protein

Protein identifiers

Protein BTG2 — P78543 (reviewed: P78543)

Alternative names: BTG family member 2, NGF-inducible anti-proliferative protein PC3

All UniProt accessions (1): P78543

UniProt curated annotations — full annotation on UniProt →

Function. Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex. Activates mRNA deadenylation in a CNOT6 and CNOT7-dependent manner. In vitro can inhibit deadenylase activity of CNOT7 and CNOT8. Involved in cell cycle regulation. Could be involved in the growth arrest and differentiation of the neuronal precursors. Modulates transcription regulation mediated by ESR1. Involved in mitochondrial depolarization and neurite outgrowth.

Subunit / interactions. Interacts with PRKCABP. Interacts with CNOT7 and CNOT8; indicative for an association with the CCR4-NOT complex. Interacts with PIN1, inducing mitochondrial depolarization.

Post-translational modifications. Phosphorylated at Ser-147 by MAPK1/ERK2 and MAPK3/ERK1, and at Ser-149 by MAPK14, leading to PIN1-binding and mitochondrial depolarization.

Similarity. Belongs to the BTG family.

RefSeq proteins (1): NP_006754* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002087	Anti_prolifrtn	Domain
IPR033332	BTG	Family
IPR036054	BTG-like_sf	Homologous_superfamily

Pfam: PF07742

UniProt features (23 total): mutagenesis site 9, helix 5, strand 4, modified residue 2, chain 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3E9V	X-RAY DIFFRACTION	1.7
3DJU	X-RAY DIFFRACTION	2.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78543-F1	86.38	0.76

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 (2): 147, 149

Mutagenesis-validated functional residues (9):

Position	Phenotype
147	impairs phosphorylation by mapk1 and mapk3, and decreases pin1-binding.
148	impairs pin1-binding.
149	impairs phosphorylation by mapk14, and decreases pin1-binding.
53	impairs interaction with cnot7 and cnot8.
65	abolishes interaction with cnot7 and cnot8.
75	abolishes interaction with cnot7 and cnot8.
103	abolishes interaction with cnot7 and cnot8; impairs anti-proliferative activity.
105	impairs interaction with cnot7 and cnot8.
115	impairs interaction with cnot7. inhibits cnot7 mrna deadenylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 590 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_DENTATE_GYRUS_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, AMIT_DELAYED_EARLY_GENES, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELLULAR_RESPONSE_TO_LIPID, SHEPARD_CRASH_AND_BURN_MUTANT_UP

GO Biological Process (22): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA repair (GO:0006281), DNA damage response (GO:0006974), neuroblast proliferation (GO:0007405), negative regulation of neuroblast proliferation (GO:0007406), negative regulation of cell population proliferation (GO:0008285), associative learning (GO:0008306), response to mechanical stimulus (GO:0009612), anterior/posterior pattern specification (GO:0009952), negative regulation of translation (GO:0017148), dentate gyrus development (GO:0021542), central nervous system neuron development (GO:0021954), neuron projection development (GO:0031175), skeletal muscle cell differentiation (GO:0035914), response to peptide hormone (GO:0043434), negative regulation of neuron apoptotic process (GO:0043524), response to electrical stimulus (GO:0051602), positive regulation of nuclear-transcribed mRNA poly(A) tail shortening (GO:0060213), cellular response to phorbol 13-acetate 12-myristate (GO:1904628), neuron differentiation (GO:0030182), negative regulation of apoptotic process (GO:0043066), neural precursor cell proliferation (GO:0061351)

GO Molecular Function (2): transcription corepressor activity (GO:0003714), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Cycle Genes	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
generation of neurons	2
response to abiotic stimulus	2
neuron development	2
cell differentiation	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
neural precursor cell proliferation	1
neuroblast proliferation	1
negative regulation of neurogenesis	1
regulation of neuroblast proliferation	1
negative regulation of neural precursor cell proliferation	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
learning	1
response to external stimulus	1
regionalization	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
hippocampus development	1
anatomical structure development	1
central nervous system neuron differentiation	1
plasma membrane bounded cell projection organization	1
skeletal muscle tissue development	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
nuclear-transcribed mRNA poly(A) tail shortening	1
regulation of nuclear-transcribed mRNA poly(A) tail shortening	1
positive regulation of mRNA catabolic process	1

Protein interactions and networks

STRING

1496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTG2	PRMT1	Q99873	981
BTG2	HOXB9	P17482	892
BTG2	CNOT7	Q9UIV1	691
BTG2	GADD45A	P24522	686
BTG2	PABPC1	P11940	643
BTG2	DUSP1	P28562	640
BTG2	NR4A1	P22736	637
BTG2	CCND1	P24385	635
BTG2	DUSP12	Q9UNI6	627
BTG2	CCN1	O00622	624
BTG2	CCNE1	P24864	618
BTG2	TP53	P04637	570
BTG2	CNOT6L	Q96LI5	570
BTG2	CDKN1A	P38936	562
BTG2	TBX20	Q9UMR3	551

IntAct

26 interactions, top by confidence:

A	B	Type	Score
BTG2	CNOT7	psi-mi:“MI:0915”(physical association)	0.800
BTG2	CNOT8	psi-mi:“MI:0915”(physical association)	0.700
CNOT8	BTG2	psi-mi:“MI:0915”(physical association)	0.700
Cnot7	BTG2	psi-mi:“MI:0915”(physical association)	0.650
Cnot7	BTG2	psi-mi:“MI:0407”(direct interaction)	0.650
BTG2	Cnot7	psi-mi:“MI:0915”(physical association)	0.650
AR	BTG2	psi-mi:“MI:0915”(physical association)	0.520
BTG2	AR	psi-mi:“MI:0915”(physical association)	0.520
BTG2	POPDC2	psi-mi:“MI:0915”(physical association)	0.370
BTG2	CNOT1	psi-mi:“MI:0915”(physical association)	0.000
BTG2	CNOT6L	psi-mi:“MI:0915”(physical association)	0.000
BTG2	CNOT7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): CNOT8 (Two-hybrid), CNOT7 (Two-hybrid), BTG2 (Biochemical Activity), BTG2 (Affinity Capture-RNA), CNOT1 (Affinity Capture-MS), CNOT6L (Affinity Capture-MS), PRMT1 (Two-hybrid), BTG2 (Reconstituted Complex), PRMT1 (Co-purification), PRMT1 (Two-hybrid), PRMT1 (Reconstituted Complex), CNOT7 (Two-hybrid), Pick1 (Two-hybrid), BTG2 (Reconstituted Complex), BTG2 (Affinity Capture-Western)

ESM2 similar proteins: A6QQA5, A7YWU3, B5XBP5, F5HA27, F5HF47, F5HG20, O36381, O36391, O36416, O36417, P03185, P03220, P0C6Z9, P0C866, P0CK56, P0CK57, P10191, P20402, P29882, P78543, Q03552, Q04566, Q07G87, Q1RMA6, Q20A00, Q2HR98, Q3KSP4, Q3KSR8, Q3TDK6, Q4V7D2, Q567C3, Q5BK64, Q5PQ92, Q5R7X1, Q5REJ0, Q5U2R2, Q66669, Q6DFN5, Q758A1, Q7ZVT5

Diamond homologs: A4UTQ2, O70552, O88677, P27049, P34743, P40744, P40745, P50615, P50616, P53348, P62324, P62325, P78543, Q04211, Q14106, Q14201, Q54NU5, Q61471, Q63073, Q8R5K6, Q9JM55, Q9NY30

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
BTG2	“up-regulates activity”	HOXB9	binding
AR	“down-regulates quantity by repression”	BTG2	“transcriptional regulation”
BTG2	“up-regulates activity”	NFE2L2	binding
BTG2	“up-regulates quantity by expression”	CAT	“transcriptional regulation”
BTG2	“up-regulates quantity by expression”	SOD2	“transcriptional regulation”
BTG2	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
BTG2	“down-regulates quantity by repression”	KLK3	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — CLLSLL, DLBCLNOS, MLYM, NHL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

181 predictions. Top by Δscore:

Variant	Effect	Δscore
1:203305708:GCT:G	donor_gain	1.0000
1:203305747:AGGT:A	donor_loss	1.0000
1:203305749:G:GG	donor_gain	1.0000
1:203305750:T:A	donor_loss	1.0000
1:203305736:G:GT	donor_gain	0.9900
1:203307087:T:TA	acceptor_gain	0.9900
1:203307100:ACAG:A	acceptor_loss	0.9900
1:203307101:CAG:C	acceptor_gain	0.9900
1:203307102:A:AG	acceptor_gain	0.9900
1:203307102:AG:A	acceptor_loss	0.9900
1:203307102:AGA:A	acceptor_gain	0.9900
1:203307103:G:GA	acceptor_loss	0.9900
1:203307103:G:GG	acceptor_gain	0.9900
1:203307103:GA:G	acceptor_gain	0.9900
1:203307103:GAG:G	acceptor_gain	0.9900
1:203307103:GAGC:G	acceptor_gain	0.9900
1:203307103:GAGCA:G	acceptor_gain	0.9900
1:203307099:CACAG:C	acceptor_gain	0.9700
1:203307100:ACAGA:A	acceptor_gain	0.9700
1:203305747:AG:A	donor_gain	0.9600
1:203305748:GG:G	donor_gain	0.9600
1:203307088:G:A	acceptor_gain	0.9600
1:203307100:A:AG	acceptor_gain	0.9600
1:203305746:CAG:C	donor_gain	0.9500
1:203306048:G:A	acceptor_gain	0.9400
1:203307093:T:A	acceptor_loss	0.9400
1:203307101:C:G	acceptor_gain	0.9400
1:203306047:C:CA	acceptor_gain	0.9100
1:203307093:T:TA	acceptor_gain	0.9100
1:203306140:G:T	donor_gain	0.8900

AlphaMissense

1035 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:203307118:C:G	H53D	0.999
1:203307123:G:C	W54C	0.999
1:203307123:G:T	W54C	0.999
1:203307124:T:C	F55L	0.999
1:203307126:T:A	F55L	0.999
1:203307126:T:G	F55L	0.999
1:203307154:T:G	Y65D	0.999
1:203307157:C:A	R66S	0.999
1:203307268:T:A	W103R	0.999
1:203307268:T:C	W103R	0.999
1:203307270:G:C	W103C	0.999
1:203307270:G:T	W103C	0.999
1:203307296:G:C	R112P	0.999
1:203305661:T:C	F19L	0.998
1:203305663:C:A	F19L	0.998
1:203305663:C:G	F19L	0.998
1:203307121:T:A	W54R	0.998
1:203307121:T:C	W54R	0.998
1:203307145:G:C	G62R	0.998
1:203307152:G:A	G64D	0.998
1:203307161:G:A	C67Y	0.998
1:203307162:C:G	C67W	0.998
1:203307278:C:A	P106H	0.998
1:203307289:T:C	S110P	0.998
1:203307292:T:G	Y111D	0.998
1:203307295:C:A	R112S	0.998
1:203305662:T:C	F19S	0.997
1:203305743:T:C	L46P	0.997
1:203307120:C:A	H53Q	0.997
1:203307120:C:G	H53Q	0.997

dbSNP variants (sampled 300 via entrez): RS1000200665 (1:203305534 G>A,T), RS1000938390 (1:203306925 T>G), RS1001236061 (1:203304477 C>T), RS1002919340 (1:203305245 C>G,T), RS1003803880 (1:203309192 C>T), RS1004409872 (1:203307366 C>T), RS1004806296 (1:203307684 C>A), RS1004884523 (1:203307545 T>C), RS1005413280 (1:203304916 T>C), RS1005478738 (1:203306317 G>A,C), RS1005819349 (1:203306106 G>A), RS1005901225 (1:203305242 T>C), RS1006441334 (1:203305436 G>A,C,T), RS1006904171 (1:203307786 A>G), RS1006935143 (1:203308074 AT>A)

Disease associations

OMIM: gene MIM:601597 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST004601_8	Red blood cell count	3.000000e-12
GCST004602_22	Mean corpuscular volume	3.000000e-27
GCST004621_40	Red cell distribution width	6.000000e-14
GCST004628_135	Immature fraction of reticulocytes	2.000000e-12
GCST004630_17	Mean corpuscular hemoglobin	4.000000e-24
GCST006804_137	Red cell distribution width	5.000000e-10
GCST90002387_239	Immature fraction of reticulocytes	4.000000e-19
GCST90002390_24	Mean corpuscular hemoglobin	1.000000e-41
GCST90002392_295	Mean corpuscular volume	1.000000e-16
GCST90002392_296	Mean corpuscular volume	6.000000e-63
GCST90002396_158	Mean reticulocyte volume	7.000000e-42
GCST90002396_159	Mean reticulocyte volume	4.000000e-167
GCST90002397_741	Mean spheric corpuscular volume	4.000000e-158
GCST90002397_790	Mean spheric corpuscular volume	8.000000e-45
GCST90002403_56	Red blood cell count	1.000000e-16
GCST90002404_439	Red cell distribution width	4.000000e-44

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0009188	Red cell distribution width
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects response to substance, increases expression	10
Benzo(a)pyrene	increases expression, increases methylation	9
Aflatoxin B1	affects expression, increases expression, affects reaction	7
Tretinoin	affects response to substance, affects localization, affects binding, decreases reaction, increases expression	5
bisphenol A	increases expression, affects cotreatment, decreases expression	4
Doxorubicin	affects reaction, increases response to substance, increases expression	3
Estradiol	affects cotreatment, decreases expression	3
Hydrogen Peroxide	affects expression, increases expression	3
sodium arsenite	decreases expression, increases abundance	2
nickel chloride	increases expression, affects reaction	2
mercuric bromide	increases expression, affects cotreatment	2
Zoledronic Acid	decreases expression, increases expression	2
Arsenic Trioxide	increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Etoposide	increases expression, increases reaction	2
Fluorouracil	increases expression, affects reaction, increases reaction	2
Formaldehyde	increases expression	2
Methyl Methanesulfonate	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Dronabinol	decreases expression, decreases response to substance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Palmitic Acid	affects cotreatment, affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
9-hydroxyoctadecadienoic acid	increases expression	1
sotorasib	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KT44	HeLa SilenciX BTG2	Cancer cell line	Female

Clinical trials (associated diseases)

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