BACH2

Chr 6AD

BTB domain and CNC homolog 2

NCBI Gene: 60468ENSG00000112182UniProt: Q9BYV9

Transcriptional regulator that acts as a 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). Is a key regulator of adaptive immunity, crucial for the maintenance of regulatory T-cell function and B-cell maturation (PubMed:28530713)

Primary Disease Associations & Inheritance

Immunodeficiency 60 and autoimmunityMIM #618394
AD
378
ClinVar variants
1
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— BACH2
🧬
Gene-Disease Validity (ClinGen)
immunodeficiency 60 · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
1 Pathogenic / Likely Pathogenic· 244 VUS of 378 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.23LOEUF
pLI 0.998
Z-score 4.46
OE 0.07 (0.03–0.23)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.30Z-score
OE missense 0.71 (0.65–0.78)
361 obs / 506.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.65–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 2 / 27.0Missense obs/exp: 361 / 506.4Syn Z: 0.01

ClinVar Variant Classifications

378 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS244
Likely Benign124
Benign5
Conflicting4
1
Pathogenic
244
VUS
124
Likely Benign
5
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
2
225
17
0
244
Likely Benign
0
2
9
113
124
Benign
0
0
4
1
5
Conflicting
—4
Total222731114378

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BACH2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency 60 and autoimmunity

MIM #618394

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
BACH2 regulates diversification of regulatory and proinflammatory chromatin states in T(H)17 cells.
Thakore PI et al.·Nat Immunol
2024
TBL1XR1 Mutations Drive Extranodal Lymphoma by Inducing a Pro-tumorigenic Memory Fate.
Venturutti L et al.·Cell
2020
Multiomic analysis of monocyte-derived alveolar macrophages in idiopathic pulmonary fibrosis.
Zhang M et al.·J Transl Med
2024
BACH2: The Future of Induced T-Regulatory Cell Therapies.
Zwick D et al.·Cells
2024Review
Single-Nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root.
Liu X et al.·Adv Sci (Weinh)
2024
Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes.
Robertson CC et al.·Nat Genet
2021
The role of Bach2 in regulating CD8 + T cell development and function.
Weng X et al.·Cell Commun Signal
2024Review
Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells.
Inaba A et al.·Nat Commun
2023
The critical role of Bach2 in regulating type 2 chronic airway inflammation.
Yamashita M et al.·Int Immunol
2018Review
BACH2 regulates T cell lineage state to enhance CAR T cell function.
Chang TC et al.·Nat Immunol
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools