BACH2

Summary

BACH2 (BACH transcriptional regulator 2, HGNC:14078) is a protein-coding gene on chromosome 6q15, encoding Transcription regulator protein BACH2 (Q9BYV9). Transcriptional regulator that acts as a repressor or activator.

Enables sequence-specific double-stranded DNA binding activity. Involved in primary adaptive immune response involving T cells and B cells. Located in cytosol and nucleoplasm. Part of RNA polymerase II transcription regulator complex. Implicated in immunodeficiency 60.

Source: NCBI Gene 60468 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 60 (Strong, GenCC)
• GWAS associations: 109
• Clinical variants (ClinVar): 618 total — 1 pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes
• MANE Select transcript: NM_021813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14078
Approved symbol	BACH2
Name	BACH transcriptional regulator 2
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	BTBD25
Ensembl gene	ENSG00000112182
Ensembl biotype	protein_coding
OMIM	605394
Entrez	60468

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000257749, ENST00000343122, ENST00000406998, ENST00000453877, ENST00000470301, ENST00000472023, ENST00000481150, ENST00000493201, ENST00000494747, ENST00000695952, ENST00000695953, ENST00000695954, ENST00000695955, ENST00000931217, ENST00000931218, ENST00000968922

RefSeq mRNA: 2 — MANE Select: NM_021813 NM_001170794, NM_021813

CCDS: CCDS5026

Canonical transcript exons

ENST00000257749 — 9 exons

Exon	Start	End
ENSE00000798242	89938144	89938350
ENSE00000918700	89950270	89951862
ENSE00001230414	90088961	90089109
ENSE00001230422	90206569	90206681
ENSE00001230434	90252513	90252590
ENSE00001230445	90271849	90271941
ENSE00003796242	90008602	90008856
ENSE00003844963	89926528	89932890
ENSE00003847104	90296480	90296843

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.5493 / max 982.9928, expressed in 1101 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74737	9.4399	923
74738	3.2968	646
74736	0.7511	242
74740	0.2700	126
74741	0.2098	99
74734	0.1737	66
74742	0.1556	64
74728	0.0776	30
74735	0.0662	37
74727	0.0572	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.45	gold quality
sural nerve	UBERON:0015488	89.56	gold quality
epithelium of nasopharynx	UBERON:0001951	87.44	gold quality
nasopharynx	UBERON:0001728	87.42	gold quality
oocyte	CL:0000023	85.87	gold quality
bone marrow	UBERON:0002371	83.42	gold quality
secondary oocyte	CL:0000655	83.18	gold quality
thymus	UBERON:0002370	83.09	gold quality
ganglionic eminence	UBERON:0004023	83.00	gold quality
tonsil	UBERON:0002372	81.38	gold quality
lymph node	UBERON:0000029	80.68	gold quality
ventricular zone	UBERON:0003053	80.52	gold quality
superficial temporal artery	UBERON:0001614	79.49	silver quality
bone marrow cell	CL:0002092	79.08	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	78.92	gold quality
vermiform appendix	UBERON:0001154	77.69	gold quality
caecum	UBERON:0001153	76.96	gold quality
calcaneal tendon	UBERON:0003701	76.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.84	gold quality
embryo	UBERON:0000922	76.66	gold quality
blood	UBERON:0000178	76.40	gold quality
granulocyte	CL:0000094	75.45	gold quality
germinal epithelium of ovary	UBERON:0001304	75.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.32	gold quality
corpus callosum	UBERON:0002336	75.16	gold quality
ileal mucosa	UBERON:0000331	74.69	gold quality
superior surface of tongue	UBERON:0007371	74.47	gold quality
colonic epithelium	UBERON:0000397	73.24	gold quality
hair follicle	UBERON:0002073	73.21	silver quality
biceps brachii	UBERON:0001507	73.13	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	798.38
E-CURD-122	yes	69.05
E-HCAD-4	yes	59.51
E-CURD-112	yes	47.41
E-ANND-3	yes	11.67
E-MTAB-9801	yes	7.41
E-MTAB-10042	yes	4.62
E-HCAD-29	no	275.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
BCL2	Unknown
CEL
FGF4	Activation
HBB	Repression
HMOX1	Repression
IL2	Unknown
PRDM1	Unknown
TP53
XBP1	Repression

JASPAR motifs

Motif	Name	Family
MA1101.1	BACH2	Jun-related
MA1101.2	BACH2	Jun-related
MA1101.3	BACH2	Jun-related
MA1470.1	BACH2	Jun-related
MA1470.2	BACH2	Jun-related

JASPAR matrix evidence (PMIDs): PMID:8887638, PMID:28461702

Upstream regulators (CollecTRI, top): PAX5

miRNA regulators (miRDB)

326 targeting BACH2, 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-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
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

Literature-anchored findings (GeneRIF, showing 40)

• BACH2 is transcriptionally regulated by the BCR/ABL oncogene. (PMID:11746976)
• antineoplastic drugs that were oxidative stressors induced the nuclear accumulation of BACH2 (PMID:12829606)
• loss of BACH2 expression through Epstein-Barr virus integration might contribute to lymphomagenesis (PMID:14982850)
• Results demonstrate that transcription activity associated with PML bodies is selectively repressed by the recruitment of Bach2 around PML bodies. (PMID:15060166)
• Upregulation of BACH2 is associated with ovarian cancer (PMID:16832351)
• Bach2 is phosphorylated on S521 via Bcr-Abl signaling thru the phosphatidylinositol-3/S6 kinase pathway,and transcriptionally represses heme oxygenase-1 (PMID:17018862)
• down-regulation of the BACH2 gene through the interaction with centromeric heterochromatin would take part in leukomogenesis of BCR-ABL positive lymphoid leukemia. (PMID:17044046)
• This study demonstrated strong integration clusters in the BACH2 gene were observed in 2 HIV infection patients without detectable viremia. (PMID:17262715)
• expression of the silencing mediator of retinoid and thyroid receptor (SMRT) & histone deacetylase4 (HDAC4) enhances formation of Bach2 foci in nuclear matrix. SMRT mediates HDAC4 binding to Bach2, & HDAC4 facilitates the retention of Bach2 in the foci. (PMID:17383980)
• This study demonstrates a novel role for Bach2 as a key regulator of nucleic acid-triggered antiviral responses in human cells. (PMID:17991429)
• reporter assays demonstrated that Bach2 and Bcl6 cooperate to repress Prdm1 through its intron enhancer region (PMID:18256039)
• BACH2 expression is necessary to maintain IL-2 production when NFAT1 protein is reduced, potentially impacting umbilical cord blood graft CD4(+) T-cell allogeneic responses (PMID:18769450)
• BACH2 may be partially responsible for regulation of BCL2 expression from the t(14;18)(q21;q34) translocation (PMID:18929412)
• This is the first report that shows the involvement of both BCL2L1 and the transcription factor BACH2 in a chromosomal rearrangement. (PMID:21412927)
• crystal structure of the human Bach2 POZ domain is reported at 2.1 A resolution (PMID:22194330)
• Downregulation of BACH2 mediated by Bcr-Abl oncoprotein via PAX5 is associated with chronic myeloid leukaemia. (PMID:22858985)
• We suggest that duodenal follicular lymphoma cells are in the memory B-cell stage, and require BACH2 instead of AID for ongoing mutation. (PMID:22899287)
• BACH2 competes with BCL6 for promoter binding and reverses BCL6-mediated repression of p53 and other cell cycle checkpoint-control genes. (PMID:23852341)
• our data suggest that BACH2 may play an essential role for somatic hypermutation of the Ig gene in B-cell lymphoma (PMID:23865571)
• Lower levels of BACH2 is associated with drug resistance in mantle cell lymphoma. (PMID:23936317)
• This study provides robust evidence for an association of rheumatoid arthritis susceptibility with genes involved in B cell differentiation (BACH2) and DNA repair (RAD51B). (PMID:24022229)
• The dynamics of Bach2 expression in response to DNA damage shows that it is a highly sensitive responder to transcription-blocking DNA lesions. (PMID:24075570)
• Our study clearly demonstrated that BACH2 is a susceptibility gene for GD in the Chinese Han population (PMID:24346624)
• BACH2 expression level is a promising predictor of prognosis for diffuse large B cell lymphoma. (PMID:24450488)
• The type 1 diabetes candidate gene BACH2 regulates proinflammatory cytokine-induced apoptotic pathways in pancreatic beta-cells by crosstalk with another candidate gene, PTPN2, and activation of JNK1 and BIM. (PMID:24608439)
• A restored BACH2 expression in BACH2-silenced gastric cancer cell lines, and knockdown of BACH2 using short hairpin RNA (i.e. RNA interference) increased cell proliferation in gastric cancer cells. (PMID:24858026)
• There were multiple independent HIV integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. (PMID:24968937)
• These observations suggested that the unstructured region of Bach2 is important for heme binding, and consequently for its functional regulation (PMID:25444856)
• Gene expression analysis revealed that three gene BACH2, PTGER4 and ZFP36L1, are down-regulated in MS patients’ blood cells compared to healthy subjects. (PMID:25670004)
• The investigated Bach2 gene polymorphisms (rs11755527, rs3757247, rs12212193 and rs2474619) are not related to the susceptibility to either Vogt-Koyanagi-Harada syndrome and Behcet’s disease in our investigated Chinese Han population. (PMID:25873652)
• The study identifies a strong association of Coeliac Disease with a network of BACH2 regulated genes, supporting emerging evidence of an important role of BACH2 in the regulation of T cell differentiation and prevention of autoimmune disease. (PMID:26444573)
• we developed a CRISPR-Cas9-based tool for specific DNA methylation consisting of deactivated Cas9 (dCas9) nuclease and catalytic domain of the DNA methyltransferase DNMT3A targeted by co-expression of a guide RNA to any 20 bp DNA sequence followed by the NGG trinucleotide.we demonstrated that directed DNA methylation of a wider promoter region of the target loci IL6ST and BACH2 decreased their expression (PMID:26969735)
• The shift in the CSDs by heme binding suggested that heme binding causes Bach2(331-520) to adopt a more compact conformation. In addition, heme binding to the CP-motif could reduce the flexibility of Bach2(331-520) Consequently, the five-coordinated heme binding destabilizes Bach2(331-520), by reducing the flexibility of the polypeptide chain. (PMID:27206783)
• genetic association studies in population in the United Kingdom: Data suggest that an SNP in BACH2 (rs3757247) is associated with autoimmune Addison’s disease and with polyglandular autoimmune syndrome type 2. These findings were replicated in a Norwegian validation cohort. (PMID:27680876)
• Ikaros regulates expression of the BCL6/BACH2 axis in acute lymphoblastic leukemia cells. (PMID:28030830)
• BACH2 downregulation contributes to constitutive activation of the nuclear factor-kappaB. (PMID:28256087)
• BACH2 haploinsufficiency causing a syndrome of immune deficiency and autoimmunity is described in two families. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation. (PMID:28530713)
• In this study silencing BACH2 in mantle cell lymphoma cells resulted in increased proliferation and enhanced tumor dispersal in hypoxic microenvironments, suggesting a tumor suppressor-like role of BACH2. (PMID:28592433)
• Data show that BACH2 and STAT5B are activated by viral insertions, generating chimeric mRNAs specifically enriched in T regulatory cells favoring their persistence. (PMID:28887441)
• The authors show that the timed repression of BACH2 through IL-2-mediated ERK/ELK1 signalling pathway directs plasma cell lineage commitment. (PMID:29129929)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	bach2b	ENSDARG00000004074
mus_musculus	Bach2	ENSMUSG00000040270
rattus_norvegicus	Bach2	ENSRNOG00000006170

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), KLHL5 (ENSG00000109790), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), IVNS1ABP (ENSG00000116679), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Transcription regulator protein BACH2 — Q9BYV9 (reviewed: Q9BYV9)

Alternative names: BTB and CNC homolog 2

All UniProt accessions (2): Q9BYV9, Q7Z6Q0

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator that acts as a repressor or activator. Binds to Maf recognition elements (MARE). Plays an important role in coordinating transcription activation and repression by MAFK. Induces apoptosis in response to oxidative stress through repression of the antiapoptotic factor HMOX1. Positively regulates the nuclear import of actin. Is a key regulator of adaptive immunity, crucial for the maintenance of regulatory T-cell function and B-cell maturation.

Subunit / interactions. Homodimer; disulfide-linked. Heterodimer of BACH2 and Maf-related transcription factors.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. B-cell specific.

Post-translational modifications. Phosphorylation at Ser-521 downstream of the PI-3K pathway promotes nuclear export. The reversible disulfide bond may provide a mechanism to regulate the activity in oxidative stress responses.

Disease relevance. Immunodeficiency 60 and autoimmunity (IMD60) [MIM:618394] An autosomal dominant primary immunologic disorder characterized by intestinal inflammation, recurrent sino-pulmonary infections, impaired lymphocyte maturation, and variably decreased immunoglobulin production. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the bZIP family. CNC subfamily.

RefSeq proteins (2): NP_001164265, NP_068585* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR004826	bZIP_Maf	Domain
IPR004827	bZIP	Domain
IPR008917	TF_DNA-bd_sf	Homologous_superfamily
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR043321	bZIP_BACH	Domain
IPR046347	bZIP_sf	Homologous_superfamily
IPR050457	ZnFinger_BTB_dom_contain	Family

Pfam: PF00651, PF03131

UniProt features (38 total): region of interest 7, strand 6, helix 5, compositionally biased region 4, sequence variant 3, domain 2, modified residue 2, cross-link 2, sequence conflict 2, chain 1, short sequence motif 1, disulfide bond 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3OHU	X-RAY DIFFRACTION	2.1
3OHV	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYV9-F1	54.66	0.21

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): 315, 521, 382, 421

Disulfide bonds (1): 20

Mutagenesis-validated functional residues (1):

Position	Phenotype
521	leads to nuclear accumulation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 528 (showing top): chr6q15, TGGTGCT_MIR29A_MIR29B_MIR29C, AAGCAAT_MIR137, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MOTAMED_RESPONSE_TO_ANDROGEN_DN, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOBP_NUCLEAR_TRANSPORT, GTGCCTT_MIR506, MARTINEZ_RB1_TARGETS_UP, HUTTMANN_B_CLL_POOR_SURVIVAL_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, OCT1_03, MODULE_301, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), import into nucleus (GO:0051170), primary adaptive immune response involving T cells and B cells (GO:0090721), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
negative regulation of DNA-templated transcription	1
nucleocytoplasmic transport	1
intercellular transport	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
primary adaptive immune response	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BACH2	MAF	O75444	993
BACH2	MAFG	O15525	944
BACH2	MAFK	O60675	940
BACH2	NCOR1	O75376	874
BACH2	MAFF	Q9ULX9	873
BACH2	IRF4	Q15306	851
BACH2	PRDM1	O75626	798
BACH2	PAX5	Q02548	783
BACH2	NCOR2	Q9Y618	777
BACH2	AICDA	Q9GZX7	767
BACH2	BATF	Q16520	761
BACH2	XBP1	P17861	710
BACH2	C1QTNF6	Q9BXI9	680
BACH2	CLEC16A	Q2KHT3	661
BACH2	PTPN2	P17706	653

IntAct

159 interactions, top by confidence:

A	B	Type	Score
BACH2	BATF3	psi-mi:“MI:0915”(physical association)	0.810
BATF3	BACH2	psi-mi:“MI:0407”(direct interaction)	0.810
MAFG	BACH2	psi-mi:“MI:0915”(physical association)	0.760
BACH2	MAFG	psi-mi:“MI:0407”(direct interaction)	0.760
MAFG	BACH2	psi-mi:“MI:0407”(direct interaction)	0.760
TULP3	BACH2	psi-mi:“MI:0915”(physical association)	0.740
MAFK	BACH2	psi-mi:“MI:0915”(physical association)	0.740
FOSL2	BACH2	psi-mi:“MI:0915”(physical association)	0.740
MAFK	BACH1	psi-mi:“MI:0914”(association)	0.730
BACH2	MAFF	psi-mi:“MI:0407”(direct interaction)	0.690
MAFF	BACH2	psi-mi:“MI:0407”(direct interaction)	0.690
ZBTB34	BACH2	psi-mi:“MI:0915”(physical association)	0.670
ZBTB24	BACH2	psi-mi:“MI:0915”(physical association)	0.670
MAFF	NFE2L1	psi-mi:“MI:0914”(association)	0.590
BACH2	HMG20A	psi-mi:“MI:0915”(physical association)	0.560
ZNF774	BACH2	psi-mi:“MI:0915”(physical association)	0.560
RPL9	BACH2	psi-mi:“MI:0915”(physical association)	0.560
MCRS1	BACH2	psi-mi:“MI:0915”(physical association)	0.560
AP1M1	BACH2	psi-mi:“MI:0915”(physical association)	0.560
BACH2	CBX8	psi-mi:“MI:0915”(physical association)	0.560
SMYD1	BACH2	psi-mi:“MI:0915”(physical association)	0.560
BACH2	CTSZ	psi-mi:“MI:0915”(physical association)	0.560
CFAP58	BACH2	psi-mi:“MI:0915”(physical association)	0.560
ANKRD55	BACH2	psi-mi:“MI:0915”(physical association)	0.560
ZNF124	BACH2	psi-mi:“MI:0915”(physical association)	0.560
BACH2	TSHZ2	psi-mi:“MI:0915”(physical association)	0.560
ZNF792	BACH2	psi-mi:“MI:0915”(physical association)	0.560
CCDC185	BACH2	psi-mi:“MI:0915”(physical association)	0.560
TRIM42	BACH2	psi-mi:“MI:0915”(physical association)	0.560
BACH2	NXF1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (112): BACH2 (Affinity Capture-MS), BACH2 (Affinity Capture-MS), BACH2 (Affinity Capture-MS), BACH2 (Affinity Capture-MS), BACH2 (Affinity Capture-MS), BACH2 (Affinity Capture-MS), MAFK (Affinity Capture-Western), BACH2 (Proximity Label-MS), BACH2 (Proximity Label-MS), BACH2 (Two-hybrid), BACH2 (Two-hybrid), BACH2 (Two-hybrid), BACH2 (Two-hybrid), BACH2 (Two-hybrid), BACH2 (Two-hybrid)

ESM2 similar proteins: A0A0A6YY25, A0A5K7RLP0, A6NMK8, A8MVX0, B2RQL2, B2RXH4, C9JSJ3, D2J0Y4, O54824, P97303, Q01954, Q05AH6, Q0VET5, Q14005, Q1W617, Q2YDE2, Q3MHT3, Q3U0P1, Q3ULM6, Q3UXL4, Q4R7L6, Q5RC05, Q5T0L3, Q68CR7, Q6GQV1, Q6NS69, Q6NZK5, Q6P1D7, Q6PG16, Q6ZVT6, Q7Z4V0, Q80W88, Q80XI1, Q811R2, Q86T90, Q86YN6, Q8BHP2, Q8BLK9, Q8BP99, Q8BW86

Diamond homologs: A0JN76, A1L2U9, A1YEX3, A1YPR0, A2AAX3, B1WAZ8, B1WBS3, B1WBU4, B2RXF5, D3ZA50, O14867, O15062, O15156, O15209, O43167, O43298, O43829, O88282, O88939, O93567, O95365, P24278, P41182, P41183, P52739, P97302, P97303, Q08376, Q0IH98, Q0IJ29, Q0P4X6, Q0VCJ6, Q13105, Q14526, Q1H9T6, Q1L8W0, Q2T9Z7, Q3B725, Q3B7N9, Q3SWU4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BACH2	“down-regulates quantity by repression”	XBP1	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	349
Likely benign	209
Benign	21

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625843	NM_021813.4(BACH2):c.71T>C (p.Leu24Pro)	Pathogenic

SpliceAI

3667 predictions. Top by Δscore:

Variant	Effect	Δscore
6:89936023:AATCC:A	donor_gain	1.0000
6:89938138:ACT:A	donor_loss	1.0000
6:89938141:C:CC	donor_loss	1.0000
6:89938142:A:AC	donor_gain	1.0000
6:89938143:C:CC	donor_gain	1.0000
6:89938143:C:G	donor_loss	1.0000
6:90008595:A:AC	donor_gain	1.0000
6:90008596:C:CC	donor_gain	1.0000
6:90008598:GTACC:G	donor_loss	1.0000
6:90008599:TAC:T	donor_loss	1.0000
6:90008600:AC:A	donor_loss	1.0000
6:90008600:ACCT:A	donor_gain	1.0000
6:90008601:CCTC:C	donor_gain	1.0000
6:90008603:T:TA	donor_gain	1.0000
6:90008619:C:CT	donor_gain	1.0000
6:90008620:C:CT	donor_gain	1.0000
6:90008709:T:TA	donor_gain	1.0000
6:90008852:ACACC:A	acceptor_gain	1.0000
6:90008853:CACC:C	acceptor_gain	1.0000
6:90008853:CACCC:C	acceptor_gain	1.0000
6:90008854:ACC:A	acceptor_gain	1.0000
6:90008855:CC:C	acceptor_gain	1.0000
6:90008855:CCC:C	acceptor_gain	1.0000
6:90008856:CC:C	acceptor_gain	1.0000
6:90008856:CCTG:C	acceptor_loss	1.0000
6:90008857:C:CA	acceptor_loss	1.0000
6:90008857:C:CC	acceptor_gain	1.0000
6:90008857:C:T	acceptor_gain	1.0000
6:90008858:T:A	acceptor_loss	1.0000
6:90206564:CTTAC:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005631 (6:90250124 T>C), RS1000008812 (6:90079443 A>T), RS1000016257 (6:90108239 T>C), RS1000017691 (6:89958011 C>T), RS1000018247 (6:90154188 T>A,C), RS1000041064 (6:90015764 A>G), RS1000045164 (6:90060988 T>C), RS1000073780 (6:90262892 C>A,T), RS1000084399 (6:89959890 G>C), RS1000085920 (6:90086229 A>C), RS1000086024 (6:90223332 G>A,T), RS1000115019 (6:90111171 C>T), RS1000115065 (6:90216561 G>C), RS1000115799 (6:90194509 C>T), RS1000124141 (6:90028253 G>C,T)

Disease associations

OMIM: gene MIM:605394 | disease phenotypes: MIM:618394, MIM:242300, MIM:608644

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 60	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immunodeficiency 60	Moderate	AD

Mondo (3): immunodeficiency 60 (MONDO:0032723), autosomal recessive congenital ichthyosis (MONDO:0017265), primary ciliary dyskinesia 3 (MONDO:0012085)

Orphanet (2): Autosomal recessive congenital ichthyosis (Orphanet:281097), Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001744	Splenomegaly
HP:0001876	Pancytopenia
HP:0001945	Fever
HP:0002028	Chronic diarrhea
HP:0002110	Bronchiectasis
HP:0002113	Pulmonary infiltrates
HP:0002206	Pulmonary fibrosis
HP:0002583	Colitis
HP:0002720	Decreased circulating IgA concentration
HP:0002850	Decreased circulating total IgM
HP:0004315	Decreased circulating IgG concentration
HP:0005425	Recurrent sinopulmonary infections
HP:0005479	Decreased circulating IgE concentration
HP:0030374	Decreased proportion of memory B cells
HP:0031808	Decreased total basophil count
HP:0032229	Perinuclear antineutrophil antibody positivity
HP:0100279	Ulcerative colitis
HP:0100280	Crohn’s disease

GWAS associations

109 associations (top):

Study	Trait	p-value
GCST000244_1	Type 1 diabetes	1.000000e-06
GCST000258_1	Type 1 diabetes	5.000000e-12
GCST000392_30	Type 1 diabetes	5.000000e-08
GCST000579_49	Cognitive performance	9.000000e-06
GCST000612_23	Celiac disease	4.000000e-10
GCST000879_66	Crohn’s disease	5.000000e-09
GCST001191_18	Type 1 diabetes	3.000000e-08
GCST001198_4	Multiple sclerosis	4.000000e-08
GCST001200_8	Graves’ disease	2.000000e-06
GCST001509_11	Vitiligo	3.000000e-08
GCST001524_9	Visceral adipose tissue/subcutaneous adipose tissue ratio	6.000000e-07
GCST001762_355	Obesity-related traits	3.000000e-06
GCST001795_11	Systemic lupus erythematosus	9.000000e-06
GCST001848_575	IgG glycosylation	5.000000e-06
GCST001848_79	IgG glycosylation	7.000000e-09
GCST002378_5	Thyroid peroxidase antibody positivity	4.000000e-08
GCST002520_1	Celiac disease	2.000000e-08
GCST003329_1	Response to anti-TNF therapy in rheumatoid arthritis	7.000000e-07
GCST003329_4	Response to anti-TNF therapy in rheumatoid arthritis	3.000000e-08
GCST003622_17	Systemic lupus erythematosus	4.000000e-12
GCST003622_7	Systemic lupus erythematosus	1.000000e-10
GCST003987_17	Asthma	7.000000e-11
GCST003988_2	Hypothyroidism	2.000000e-07
GCST004030_5	Primary sclerosing cholangitis	1.000000e-09
GCST004131_53	Inflammatory bowel disease	2.000000e-09
GCST004132_27	Crohn’s disease	6.000000e-09
GCST004383_1	Thyroid peroxidase autoantibody levels in type 1 diabetes	1.000000e-06
GCST004600_26	Eosinophil percentage of white cells	2.000000e-20
GCST004602_114	Mean corpuscular volume	9.000000e-10
GCST004606_143	Eosinophil count	1.000000e-27

EFO canonical traits (31, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0005115	metabolic rate measurement
EFO:0005193	serum IgG glycosylation measurement
EFO:0004653	response to TNF antagonist
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004587	lymphocyte count
EFO:0008378	mosquito bite reaction size measurement
EFO:0004810	interleukin-6 measurement
EFO:0004531	urate measurement
EFO:0009706	latent autoimmune diabetes in adults
EFO:0008579	risk-taking behaviour
EFO:0004847	age at onset
EFO:1002011	adult onset asthma
EFO:0009933	Thyroid preparation use measurement
EFO:0009941	Inhalant adrenergic use measurement
EFO:0009942	Glucocorticoid use measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0010176	keratinocyte carcinoma
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535278	Primary ciliary dyskinesia, 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5069364 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment, decreases expression, affects expression	6
methylmercuric chloride	increases expression, decreases expression	2
Acetaminophen	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
TAK-243	decreases sumoylation	1
sotorasib	decreases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
bis(tri-n-butyltin)oxide	increases expression	1
deoxynivalenol	increases expression	1
trichostatin A	decreases expression	1
sodium arsenite	increases expression	1
arsenic trichloride	affects binding, affects reaction	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	decreases expression	1
NSC 689534	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Anisomycin	increases expression	1
Vehicle Emissions	increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Phenylmercuric Acetate	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5059497	Binding	Proteomics fold change data (SUDHL4 cells, 1h)	Data for DCP probe CCT369260

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1967	BLUE-1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03041038	PHASE2	COMPLETED	The Efficacy and Safety of Secukinumab in Patients With Ichthyoses
NCT05312073	Not specified	COMPLETED	Study of in Vivo and in Vitro Transcriptomic and Proteomic Signatures in Unhereditary Ichtyosis