BACH2

protein-coding

BTB domain and CNC homolog 2, the group of BTB domain containing|Basic leucine zipper proteins

Gene summary

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. Implicated in immunodeficiency 60. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_021813.4

Inheritance

ClinVar variants

P:1U:345B:233

Top phenotype

Immunodeficiency 60 and autoimmunity

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr6:89,926,528-90,296,843

External References & Databases

Ensembl (ENSG00000112182)

Transcript & Mutation Effects

hg38 • Region Span ~370.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency 60STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032723

Submitter: Labcorp Genetics (formerly Invitae)

immunodeficiency 60MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032723

Submitter: ClinGen

BACH2 is a transcription factor that forms a heterodimer with MAF transcription factors to bind MAF recognition elements (MAREs) in the promoters of target genes. Bach2 deficiency significantly affected the expression of genes with super-enhancer architecture compared to those with TEs or no enhancer mark in T cells. *BACH2* was first reported in relation to in 2017 (PMID: 28530713). A de novo heterozygous c.71T>C transition in the BACH2 gene, resulting in a leu24-to-pro (L24P) substitution was detected in a female with lymphocyte maturation defects, causing immunoglobulin deficiency and intestinal inflammation. Recurrent sinopulmonary infections, bronchiectasis and intestinal inflammation were also evident in a father and his daughter with a heterozygous point mutation in BACH2, c.2362G>A. Experimental evidence also supports a haploinsufficient model. Bach2+/− mice had a significant reduction in FoxP3+ cells together with significant increases in CCR9+ and β7-integrin+ cells in CD4+ T cells. Immunized Bach2+/− mice exhibited minimal induction of both IgG1 class switched-B220hiCD138− B cells and B220loCD138+ plasma cells compared to WT mice (PMID: 28530713). The immunophenotype of patients with mutations in BACH2 consisted of compromised Treg cells, enhanced TH1 differentiation, impaired proliferation and defective B cell maturation and Ig class switching. Silencing BACH2 in healthy control B cells, significantly suppressed in vitro class switch recombination towards the IgG and IgA isotypes. In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. Gene Clinical Validity Standard Operating Procedures (SOP) - SOP9

immunodeficiency 60LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032723

Submitter: Illumina

immunodeficiency 60STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032723

Submitter: PanelApp Australia

immunodeficiency 60MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032723

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Immunodeficiency 60 and autoimmunityAD

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals may manifest with findings such as inflammatory bowel disease and recurrent sinopulmonary infections and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial

Refs: 28530713

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BACH2 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 545

not specifiedTotal: 147

BACH2-related disorderTotal: 34

Immunodeficiency 60Total: 20

Primary ciliary dyskinesia 3Total: 1

Autosomal recessive congenital ichthyosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021813.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	199 clinvar	4 clinvar	204
missense	1 clinvar		337 clinvar	29 clinvar	1 clinvar	368
nonsense			2 clinvar			2
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	345	228	5	579

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021813.4	RefSeq	NP_068585.1	4	MANE Select
ENST00000257749.9	Ensembl	ENSP00000257749.4	4	MANE Select
NM_001170794.2	RefSeq	NP_001164265.1	4	Standard
ENST00000343122.7	Ensembl	ENSP00000345642.3	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription, DNA-templated
import into nucleus

Molecular Function

RNA polymerase II distal enhancer sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA-binding transcription factor activity

Cellular Component

nucleus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257749
Coding exons: 4
Length: 370380
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125743
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.30	361	506	0.713	0.0000313	5523
Missense (PolyPhen)		83	165.59	0.50125		1858
Synonymous	0.00675	219	219	0.999	0.0000151	1673
Loss of Function	4.46	2	27.0	0.0740	0.00000133	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional regulator that acts as repressor or activator (By similarity). Binds to Maf recognition elements (MARE) (By similarity). Plays an important role in coordinating transcription activation and repression by MAFK (By similarity). Induces apoptosis in response to oxidative stress through repression of the antiapoptotic factor HMOX1 (PubMed:17018862). Positively regulates the nuclear import of actin (By similarity). {ECO:0000250|UniProtKB:P97303, ECO:0000269|PubMed:17018862}.;

Recessive Scores

pRec: 0.176

Intolerance Scores

LoFtool: 0.0845
RVIS EVS: -0.62
RVIS percentile EVS: 17.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.761

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium