BATF

Summary

BATF (basic leucine zipper ATF-like transcription factor, HGNC:958) is a protein-coding gene on chromosome 14q24.3, encoding Basic leucine zipper transcriptional factor ATF-like (Q16520). AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system: specifically mediates the differentiation of T-helper 17 cells (Th17), follicular T-helper cells (TfH), CD8(+) dendritic cells and class-switch recombination (CSR)….

The protein encoded by this gene is a nuclear basic leucine zipper protein that belongs to the AP-1/ATF superfamily of transcription factors. The leucine zipper of this protein mediates dimerization with members of the Jun family of proteins. This protein is thought to be a negative regulator of AP-1/ATF transcriptional events.

Source: NCBI Gene 10538 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 14 total — 1 pathogenic
• GTEx eGene: eQTL in 14 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.56 (intermediate), LOEUF 0.74 (unconstrained)
• Transcription factor: yes — 17 downstream targets (CollecTRI)
• MANE Select transcript: NM_006399
• Interaction hub: 1,802 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:958
Approved symbol	BATF
Name	basic leucine zipper ATF-like transcription factor
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	B-ATF, SFA-2, BATF1
Ensembl gene	ENSG00000156127
Ensembl biotype	protein_coding
OMIM	612476
Entrez	10538

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000286639

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 1

ENST00000286639, ENST00000555504, ENST00000555795

RefSeq mRNA: 1 — MANE Select: NM_006399 NM_006399

CCDS: CCDS9843

Canonical transcript exons

ENST00000286639 — 3 exons

Exon	Start	End
ENSE00001024690	75546462	75546992
ENSE00001129828	75522469	75522745
ENSE00003600201	75525084	75525188

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 95.30.

FANTOM5 (CAGE): breadth broad, TPM avg 15.1964 / max 934.2669, expressed in 731 samples.

Highest expression (Bgee): granulocyte, blood, leukocyte, monocyte, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BATF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Heart Atrial Appendage	eqtl	3.2e-08	-0.20	14:75536121:C:G
Artery Tibial	eqtl	9.1e-07	-0.19	14:75519261:A:T
Artery Coronary	eqtl	2.4e-04	-0.26	14:75527597:G:C
Breast Mammary Tissue	eqtl	2.5e-04	-0.14	14:75536121:C:G
Lung	eqtl	8.5e-04	-0.16	14:75519261:A:T
Minor Salivary Gland	eqtl	1.2e-03	-0.26	14:75527597:G:C
Thyroid	eqtl	2.0e-03	-0.12	14:75532722:T:G
Heart Left Ventricle	eqtl	2.5e-03	-0.19	14:75534516:T:C
Adipose Subcutaneous	eqtl	4.9e-03	-0.12	14:75520236:A:G
Whole Blood	eqtl	6.2e-03	-0.07	14:75532722:T:G
Ovary	eqtl	2.0e-02	-1.22	14:76049486:A:G
Skin Sun Exposed Lower leg	eqtl	2.0e-02	-0.11	14:75506004:C:T
Testis	eqtl	2.7e-02	-0.33	14:75520291:C:T
Brain Nucleus accumbens basal ganglia	eqtl	3.2e-02	-0.99	14:76415275:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
140681	9.7821	705
140682	4.6214	410
140683	0.6268	176
207301	0.1661	96

Top tissues by expression

showing 100 of 272 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.30	gold quality
blood	UBERON:0000178	88.33	gold quality
leukocyte	CL:0000738	86.00	gold quality
monocyte	CL:0000576	85.51	gold quality
mononuclear cell	CL:0000842	85.48	gold quality
spleen	UBERON:0002106	85.47	gold quality
lymph node	UBERON:0000029	85.16	gold quality
vermiform appendix	UBERON:0001154	84.81	gold quality
palpebral conjunctiva	UBERON:0001812	84.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.11	gold quality
bone marrow	UBERON:0002371	82.05	gold quality
caecum	UBERON:0001153	80.67	gold quality
endometrium epithelium	UBERON:0004811	80.19	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	79.94	gold quality
cartilage tissue	UBERON:0002418	79.93	silver quality
amniotic fluid	UBERON:0000173	79.35	gold quality
trabecular bone tissue	UBERON:0002483	78.81	gold quality
urinary bladder	UBERON:0001255	78.52	gold quality
mucosa of urinary bladder	UBERON:0001259	78.20	silver quality
nasal cavity epithelium	UBERON:0005384	78.20	silver quality
gluteal muscle	UBERON:0002000	76.64	gold quality
nasal cavity mucosa	UBERON:0001826	76.63	gold quality
bone marrow cell	CL:0002092	76.18	gold quality
triceps brachii	UBERON:0001509	75.71	gold quality
gall bladder	UBERON:0002110	75.43	gold quality
upper lobe of left lung	UBERON:0008952	75.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.31	gold quality
periodontal ligament	UBERON:0008266	74.97	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.71	gold quality
upper lobe of lung	UBERON:0008948	74.69	gold quality
mucosa of transverse colon	UBERON:0004991	74.61	gold quality
tonsil	UBERON:0002372	74.38	gold quality
biceps brachii	UBERON:0001507	74.16	gold quality
tongue squamous epithelium	UBERON:0006919	74.16	gold quality
ileal mucosa	UBERON:0000331	73.63	silver quality
saliva-secreting gland	UBERON:0001044	73.23	gold quality
buccal mucosa cell	CL:0002336	73.22	gold quality
omental fat pad	UBERON:0010414	73.01	gold quality
peritoneum	UBERON:0002358	72.97	gold quality
epithelium of nasopharynx	UBERON:0001951	72.51	silver quality
body of stomach	UBERON:0001161	72.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	72.37	gold quality
minor salivary gland	UBERON:0001830	72.31	gold quality
small intestine	UBERON:0002108	72.19	gold quality
superficial temporal artery	UBERON:0001614	71.74	silver quality
mouth mucosa	UBERON:0003729	71.39	gold quality
left coronary artery	UBERON:0001626	70.10	gold quality
right lung	UBERON:0002167	69.97	gold quality
pancreatic ductal cell	CL:0002079	69.76	silver quality
inferior olivary complex	UBERON:0002127	69.60	gold quality
caudate nucleus	UBERON:0001873	69.50	gold quality
coronary artery	UBERON:0001621	69.30	gold quality
mammary gland	UBERON:0001911	69.13	gold quality
thoracic mammary gland	UBERON:0005200	69.00	gold quality
stomach	UBERON:0000945	68.94	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	68.91	gold quality
subcutaneous adipose tissue	UBERON:0002190	68.62	gold quality
placenta	UBERON:0001987	68.61	gold quality
right coronary artery	UBERON:0001625	68.55	gold quality
putamen	UBERON:0001874	68.46	gold quality
left uterine tube	UBERON:0001303	68.40	gold quality
colonic mucosa	UBERON:0000317	68.18	gold quality
mucosa of sigmoid colon	UBERON:0004993	68.02	silver quality
adipose tissue	UBERON:0001013	68.01	gold quality
tendon of biceps brachii	UBERON:0008188	67.93	silver quality
lower esophagus muscularis layer	UBERON:0035833	67.92	gold quality
connective tissue	UBERON:0002384	67.90	gold quality
skin of leg	UBERON:0001511	67.85	gold quality
lung	UBERON:0002048	67.85	gold quality
lower esophagus	UBERON:0013473	67.85	gold quality
smooth muscle tissue	UBERON:0001135	67.70	gold quality
gingival epithelium	UBERON:0001949	67.63	gold quality
olfactory bulb	UBERON:0002264	67.46	gold quality
transverse colon	UBERON:0001157	67.33	gold quality
skin of abdomen	UBERON:0001416	67.31	gold quality
upper leg skin	UBERON:0004262	67.18	silver quality
seminal vesicle	UBERON:0000998	67.17	silver quality
type B pancreatic cell	CL:0000169	67.15	gold quality
mammalian vulva	UBERON:0000997	67.05	silver quality
esophagus	UBERON:0001043	66.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	66.85	gold quality
cervix squamous epithelium	UBERON:0006922	66.74	gold quality
intestine	UBERON:0000160	66.70	gold quality
zone of skin	UBERON:0000014	66.60	gold quality
fundus of stomach	UBERON:0001160	66.52	gold quality
mucosa of stomach	UBERON:0001199	66.47	gold quality
prostate gland	UBERON:0002367	66.45	gold quality
esophagus mucosa	UBERON:0002469	66.27	gold quality
epithelium of bronchus	UBERON:0002031	66.26	silver quality
bronchus	UBERON:0002185	66.03	silver quality
skeletal muscle tissue	UBERON:0001134	65.77	gold quality
colon	UBERON:0001155	65.76	gold quality
large intestine	UBERON:0000059	65.70	gold quality
bronchial epithelial cell	CL:0002328	65.69	silver quality
descending thoracic aorta	UBERON:0002345	65.66	gold quality
thoracic aorta	UBERON:0001515	65.64	gold quality
oral cavity	UBERON:0000167	65.63	silver quality
mammary duct	UBERON:0001765	65.58	silver quality
duodenum	UBERON:0002114	65.51	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-CURD-95	yes	1281.02
E-MTAB-8142	yes	1177.22
E-MTAB-8410	yes	981.71
E-MTAB-6653	yes	932.12
E-HCAD-15	yes	912.91
E-GEOD-139324	yes	879.18
E-CURD-46	yes	628.71
E-HCAD-8	yes	67.89
E-CURD-88	yes	36.62
E-CURD-120	yes	36.18
E-CURD-122	yes	36.05
E-ANND-3	yes	19.06
E-HCAD-1	yes	18.71
E-GEOD-130148	yes	7.16
E-CURD-97	no	1553.92

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Lymph node	tissue	28.7	not detected
Bone marrow	tissue	20.5	not detected
Appendix	tissue	19.3	low
Tonsil	tissue	19.1	not detected
Urinary bladder	tissue	17.0	not detected
Spleen	tissue	10.1	not detected
Parathyroid gland	tissue	7.5	not detected
Stomach 1	tissue	7.4	not detected
Breast	tissue	7.3	not detected
Thymus	tissue	6.7
Salivary gland	tissue	6.1	not detected
Gallbladder	tissue	5.4	not detected
Adipose tissue	tissue	4.7	not detected
Lung	tissue	4.5	not detected
Placenta	tissue	3.8	not detected
Small intestine	tissue	3.3	not detected
Vagina	tissue	3.1	not detected
Esophagus	tissue	2.7	not detected
Colon	tissue	2.6	low
Duodenum	tissue	2.5	low
Cervix	tissue	2.1	not detected
Smooth muscle	tissue	2.1	not detected
Seminal vesicle	tissue	1.7	not detected
Spinal cord	tissue	1.6
Skin 1	tissue	1.4	not detected
Rectum	tissue	1.3	not detected
Epididymis	tissue	1.1	not detected
Liver	tissue	1.1	low
Prostate	tissue	1.1	not detected
Hippocampal formation	tissue	1.1
Medulla oblongata	tissue	1.0
Tongue	tissue	0.9
Hypothalamus	tissue	0.8
Corpus callosum	tissue	0.8
Pancreas	tissue	0.7	not detected
Midbrain	tissue	0.7
Substantia nigra	tissue	0.7
Fallopian tube	tissue	0.7	not detected
Pituitary gland	tissue	0.6
Testis	tissue	0.6	high
Heart muscle	tissue	0.6	low
Basal ganglia	tissue	0.6	not detected
Choroid plexus	tissue	0.6
Thalamus	tissue	0.6
Adrenal gland	tissue	0.6	not detected
Periaqueductal gray	tissue	0.6
Septum	tissue	0.6
Pons	tissue	0.5
Endometrium 1	tissue	0.5	not detected
Superior colliculi	tissue	0.5
Ventral forebrain	tissue	0.5
Putamen	tissue	0.4
Amygdala	tissue	0.4
Locus coeruleus	tissue	0.4
Hippocampus	tissue	0.4	not detected
Cerebral cortex	tissue	0.3	low
Nucleus accumbens	tissue	0.3
Thyroid gland	tissue	0.3	not detected
Olfactory bulb	tissue	0.3
Temporal cortex	tissue	0.3

Brain sub-regions (HPA Brain Atlas): detected in 176; highest nTPM — Blood vessel (4.2), Anterior thalamic nucleus, ventral (2.8), Caudate nucleus (2.1), Dorsal tegmental nucleus (1.9), Dorsal spinal cord (1.6).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

17 targets:

Target	Regulation
CCR9
CD2	Unknown
CD8A
IGBP1
IL10	Activation
IL17A	Activation
IL21	Activation
IL23A	Activation
IL4	Activation
IRF4	Activation
MAF	Activation
RARA
SIRT1
SLC11A1
SNCA
STAT3	Unknown
TBXT

JASPAR motifs

Motif	Name	Family
MA0462.1	BATF::JUN	B-ATF-related factors,Jun-related
MA0462.2	BATF::JUN	B-ATF-related factors,Jun-related
MA0462.3	BATF::JUN	B-ATF-related factors,Jun-related
MA1634.1	BATF	B-ATF-related factors
MA1634.2	BATF	B-ATF-related factors

JASPAR matrix evidence (PMIDs): PMID:8570175, PMID:22992523, PMID:29588546

Upstream regulators (CollecTRI, top): STAT3, STAT6

miRNA regulators (miRDB)

Targeting BATF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

8 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-4734	88.28	63.44	87
HSA-MIR-4707-3P	86.55	62.02	99

Functional genomics

gnomAD constraint: pLI 0.563, LOEUF 0.739, missense Z 1.32 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000286639 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
14:75,522,683–75,546,563	65 / 113.3	0.57	no
14:75,546,564–75,546,668	59 / 49.7	1.19	no

Literature-anchored findings (GeneRIF, showing 24)

• Overexpression of human BATF in transgenic mice disrupts the development of thymus-derived NKT cells (PMID:12594265)
• up-regulated dramatically within 24 h following the infection of established and primary human B cells with EBV by the action of EBNA2 and activated Notch protein (PMID:12719594)
• Phosphorylation of serine-43 converts BATF from a DNA binding into a non-DNA binding inhibitor of activator protein-1 activity. (PMID:12809553)
• PD-1 inhibits T cell function by upregulating BATF. (PMID:20890291)
• The activator protein 1 (AP1) family transcription factor BATF (B cell, activating transcription factor-like) was among the genes enriched in Th9 cells and was required for the expression of IL-9 and other Th9-associated genes. (PMID:24216482)
• increase expression in children with recurrent asthma (PMID:24290279)
• Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorgammaT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung (PMID:25491772)
• data strongly support a model in which EBNA3A is tethered to DNA through a BATF-containing protein complexes to enable continuous cell proliferation (PMID:25540416)
• BATF plays a key role in the differentiation of T helper cell subsets and Ig class-switching. Apart from that we suggest an important function in mast cell development and in murine models of allergic asthma, it was observed that mice deficient for Batf are protected from the disease. Hence, the previous findings on BATF make it an interesting target for the treatment of Th cell-derived-cytokine-driven diseases. (PMID:26970726)
• Retinoic acid signaling and BATF productions are activated in IgAN patients compared with controls. (PMID:27073891)
• BATF/JUN-B and BATF/C-JUN complexes play important roles in OA cartilage destruction through regulating anabolic and catabolic gene expression in chondrocytes. (PMID:27147707)
• Findings demonstrate that peripheral and intrahepatic BATF expressions are dramatically increased in chronic hepatitis B (CHB) patients, which might boost the differentiation of Th17 cells and the release of associated cytokine during chronic HBV infection. (PMID:29164410)
• BATF-dependent pathogenic GM-CSF+ effector T cells are critical promoters of intestinal inflammation in graft-versus-host disease (PMID:29376889)
• results reveal that JunB, c-Jun, and Bach2 cooperate with BATF to contribute to the specificity of BATF-dependent cytokine induction in Th subsets. (PMID:31451674)
• Prognostic Value of DNA Methylation-Driven Genes in Clear Cell Renal Cell Carcinoma: A Study Based on Methylation and Transcriptome Analyses. (PMID:32733620)
• Supervised machine learning algorithm identified KRT20, BATF and TP63 as biologically relevant biomarkers for bladder biopsy specimens from interstitial cystitis/bladder pain syndrome patients. (PMID:35102612)
• A systematic comparison of FOSL1, FOSL2 and BATF-mediated transcriptional regulation during early human Th17 differentiation. (PMID:35511484)
• BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors. (PMID:36206353)
• Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells. (PMID:36240777)
• BATF reprograms the tumor immune status. (PMID:36640752)
• Relative Expression of BATF and CD112 in PBMC of Patients with Chronic Lymphocytic Leukemia. (PMID:37378949)
• Integrated BATF transcriptional network regulates suppressive intratumoral regulatory T cells. (PMID:37713508)
• BATF promotes extramedullary infiltration through TGF-beta1/Smad/MMPs axis in acute myeloid leukemia. (PMID:38477642)
• BATF is a major driver of NK cell epigenetic reprogramming and dysfunction in AML. (PMID:39259809)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	batf	ENSDARG00000011818
mus_musculus	Batf	ENSMUSG00000034266
rattus_norvegicus	Batf	ENSRNOG00000008588
drosophila_melanogaster	Atf3	FBGN0028550

Paralogs (8): FOSL2 (ENSG00000075426), BATF3 (ENSG00000123685), FOSB (ENSG00000125740), JDP2 (ENSG00000140044), ATF3 (ENSG00000162772), BATF2 (ENSG00000168062), FOS (ENSG00000170345), FOSL1 (ENSG00000175592)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1859147) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 17 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased interleukin-17 secretion	2
decreased IgM level	1
decreased IgA level	1
decreased IgE level	1
decreased susceptibility to experimental autoimmune encephalomyelitis	1
abnormal class switch recombination	1
decreased CD4-positive, alpha-beta T cell number	1
abnormal CD4-positive T cell differentiation	1
abnormal T-helper 2 cell differentiation	1
absent germinal center B cells	1
decreased IgG1 level	1
decreased interleukin-4 secretion	1
decreased IgG2c level	1
decreased interleukin-21 secretion	1
decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number	1
decreased T follicular helper cell number	1
decreased T-helper 17 cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	P11939	100.0%	Diamond
Ovis aries	O02761	99.0%	Diamond
Mesocricetus auratus	O88479	97.6%	Diamond
Cricetiscus campbelli	Q56TT7	97.6%	Diamond
Phodopus roborovskii	Q56TN0	97.4%	Diamond
Bos taurus	O77628	97.1%	Diamond
Felis catus	Q8HZP6	97.1%	Diamond
Cricetulus griseus	Q9Z2Q8	96.9%	Diamond
Sus scrofa	O97930	96.8%	Diamond
Xenopus laevis	A1L2X1	80.0%	Diamond
Xenopus tropicalis	F7EMX9	80.0%	Diamond
Avian retrovirus NK24	P23050	100.0%	Diamond
FBJ murine osteosarcoma virus	P01102	98.5%	Diamond
Finkel-Biskis-Jinkins murine sarcoma virus	P29176	89.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
JDP2	protein-coding	122953
LINC01220	ncRNA	731223
FLVCR2	protein-coding	55640
JDP2-AS1	ncRNA	101928377
FLVCR2-AS1	ncRNA	102724153
ERG28	protein-coding	11161
TTLL5	protein-coding	23093

Protein

Protein identifiers

Basic leucine zipper transcriptional factor ATF-like — Q16520 (reviewed: Q16520)

Alternative names: B-cell-activating transcription factor, SF-HT-activated gene 2 protein

All UniProt accessions (2): Q16520, G3V266

UniProt curated annotations — full annotation on UniProt →

Function. AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system: specifically mediates the differentiation of T-helper 17 cells (Th17), follicular T-helper cells (TfH), CD8(+) dendritic cells and class-switch recombination (CSR) in B-cells. Acts via the formation of a heterodimer with JUNB that recognizes and binds DNA sequence 5’-TGA[CG]TCA-3’. The BATF-JUNB heterodimer also forms a complex with IRF4 (or IRF8) in immune cells, leading to recognition of AICE sequence (5’-TGAnTCA/GAAA-3’), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 (or IRF8) and activation of genes. Controls differentiation of T-helper cells producing interleukin-17 (Th17 cells) by binding to Th17-associated gene promoters: regulates expression of the transcription factor RORC itself and RORC target genes such as IL17 (IL17A or IL17B). Also involved in differentiation of follicular T-helper cells (TfH) by directing expression of BCL6 and MAF. In B-cells, involved in class-switch recombination (CSR) by controlling the expression of both AICDA and of germline transcripts of the intervening heavy-chain region and constant heavy-chain region (I(H)-C(H)). Following infection, can participate in CD8(+) dendritic cell differentiation via interaction with IRF4 and IRF8 to mediate cooperative gene activation. Regulates effector CD8(+) T-cell differentiation by regulating expression of SIRT1. Following DNA damage, part of a differentiation checkpoint that limits self-renewal of hematopoietic stem cells (HSCs): up-regulated by STAT3, leading to differentiation of HSCs, thereby restricting self-renewal of HSCs.

Subunit / interactions. Heterodimer; mainly heterodimerizes with JUNB. The BATF-JUNB heterodimer interacts with IRF4 and IRF8. Interacts (via bZIP domain) with IRF4 and IRF8; the interaction is direct. Also forms heterodimers with JUN and JUND. Also interacts with IFI35.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed at highest levels in lung, and at lower levels in placenta, liver, kidney, spleen, and peripheral blood. Detected in SW480 colorectal cancer cell line and several hematopoietic tumor cell lines, including Raji Burkitt’s lymphoma. Strongly expressed in mature B- and T-lymphocytes. Also expressed in moderate levels in lymph node and appendix and at low levels in thymus and bone marrow.

Post-translational modifications. Phosphorylated on serine and threonine residues and at least one tyrosine residue. Phosphorylation at Ser-43 inhibit DNA binding activity and transforms it as a negative regulator of AP-1 mediated transcription. Phosphorylated.

Induction. Up-regulated by PDCD1 following infection by HIV-1 virus, leading to inhibit T-cell functions and exhaust T-cells. Up-regulated by Epstein-Barr virus (EBV) protein EBNA2 following infection by EBV.

Similarity. Belongs to the bZIP family.

RefSeq proteins (1): NP_006390* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000837	AP-1	Family
IPR004827	bZIP	Domain
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF00170

UniProt features (8 total): region of interest 3, modified residue 2, chain 1, domain 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16520-F1	81.59	0.56

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Basic domains

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

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)

Type	Positions
Phosphoserine	43
Phosphothreonine	48

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	curated
R-HSA-9938027	Affinity selection of immunoglobulins	electronic
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	electronic
R-HSA-168256	Immune System	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-9938024	Somatic hypermutation of immunoglobulin genes	electronic

MSigDB gene sets: 366 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, LU_IL4_SIGNALING, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOZGIT_ESR1_TARGETS_DN, GOBP_REGULATION_OF_T_HELPER_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, RACCACAR_AML_Q6

GO Biological Process (18): positive regulation of cytokine production (GO:0001819), lymphoid progenitor cell differentiation (GO:0002320), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), DNA damage response (GO:0006974), DNA damage response, signal transduction by p53 class mediator (GO:0030330), defense response to protozoan (GO:0042832), myeloid dendritic cell differentiation (GO:0043011), T-helper 2 cell differentiation (GO:0045064), isotype switching (GO:0045190), hematopoietic stem cell differentiation (GO:0060218), T-helper 17 cell differentiation (GO:0072539), T-helper 17 cell lineage commitment (GO:0072540), integrated stress response signaling (GO:0140467), regulation of T-helper 17 cell differentiation (GO:2000319), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (8): 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 activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Signaling by Interleukins	1
Affinity selection of immunoglobulins	1
Immunoglobulin maturation	1
Differentiation of T cells	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

56 GO namespaces:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
hematopoietic progenitor cell differentiation	2
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
cellular response to stress	2
alpha-beta T cell activation involved in immune response	2
T cell differentiation involved in immune response	2
T-helper cell differentiation	2
T-helper 17 cell differentiation	2
regulation of transcription by RNA polymerase II	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
gene expression	1
RNA biosynthetic process	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
response to protozoan	1
defense response to other organism	1
myeloid dendritic cell activation	1
myeloid leukocyte differentiation	1
dendritic cell differentiation	1
type 2 immune response	1
somatic recombination of immunoglobulin genes involved in immune response	1
B cell activation involved in immune response	1
stem cell differentiation	1
T-helper 17 type immune response	1
T-helper cell lineage commitment	1
intracellular signaling cassette	1
regulation of immune effector process	1
regulation of T-helper cell differentiation	1
regulation of T-helper 17 type immune response	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay
sequence-specific double-stranded DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,802 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BATF	IRF4	Q15306	791
BATF	PDCD1	Q15116	784
BATF	JUND	P17535	761
BATF	BCL6	P41182	739
BATF	CD8A	P01732	705
BATF	RORC	P51449	697
BATF	CXCR5	P32302	696
BATF	TBX21	Q9UL17	682
BATF	PRDM1	O75626	680
BATF	IL17F	Q96PD4	666
BATF	MAF	O75444	661
BATF	IL22	Q9GZX6	660
BATF	RORA	P35397	644
BATF	CD4	P01730	629
BATF	PDCD1LG2	Q9BQ51	623

IntAct

Human interaction partners of BATF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 35 partners by confidence:

Partner	Interaction type	MIscore	Records
JUNB	physical association	0.970	45
DDIT3	direct interaction	0.850	9
CEBPG	direct interaction	0.620	4
JUN	direct interaction	0.620	4
ATF4	direct interaction	0.620	3
CEBPA	direct interaction	0.620	3
HLF	direct interaction	0.620	2
HTT	physical association	0.560	12
COX8A	physical association	0.560	3
DMWD	physical association	0.560	3
FGFR3	physical association	0.560	3
GARS1	physical association	0.560	3
GLE1	physical association	0.560	3
GOPC	physical association	0.560	3
GSN	physical association	0.560	3
KIF1B	physical association	0.560	3
PEX1	physical association	0.560	3
PRPS1	physical association	0.560	3
SPRED1	physical association	0.560	3
WFS1	physical association	0.560	3
ATF2	direct interaction	0.440	2
ATF3	direct interaction	0.440	2
CEBPB	direct interaction	0.440	2
CEBPE	direct interaction	0.440	2
DBP	direct interaction	0.440	2
JUND	direct interaction	0.440	2
ATF5	direct interaction	0.440	1
BACH1	direct interaction	0.440	1
BATF3	direct interaction	0.440	1
CEBPD	direct interaction	0.440	1

BioGRID (45 interactions; top human partners by supporting records): JUNB (Two-hybrid; 11 records), DDIT3 (Two-hybrid; 5 records), ATF2 (FRET; 2 records), ATF3 (FRET; 2 records), ATF4 (FRET; 2 records), BATF3 (FRET; 2 records), CEBPA (FRET; 2 records), CEBPE (FRET; 2 records), CEBPG (FRET; 2 records), DBP (FRET; 2 records), IFI35 (Two-hybrid; 2 records), CEBPB (Affinity Capture-MS), COX8A (Two-hybrid), EPAS1 (FRET), GOPC (Two-hybrid)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
BATF	“form complex”	“BZIP transcription factor complex, BATF-ATF3”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
Response of EIF2AK1 (HRI) to heme deficiency	6	138.2×	4e-10
ATF4 activates genes in response to endoplasmic reticulum stress	5	65.8×	1e-06
Cellular response to starvation	5	26.7×	5e-05
Response of EIF2AK4 (GCN2) to amino acid deficiency	6	21.5×	2e-05
Signaling by Interleukins	5	10.3×	2e-03
Cellular responses to stress	8	9.5×	5e-05
Diseases of signal transduction by growth factor receptors and second messengers	5	9.2×	2e-03
Cellular responses to stimuli	8	8.1×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	10	206.5×	3e-19
response to endoplasmic reticulum stress	7	34.4×	1e-07
liver development	5	32.6×	4e-05
regulation of cell cycle	5	11.0×	2e-03
transcription by RNA polymerase II	5	10.4×	3e-03
positive regulation of gene expression	8	9.1×	1e-04

Disease & clinical

Genetic variants

Variant evidence for BATF: 14 ClinVar records (1 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	11
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
144734	GRCh38/hg38 14q24.1-31.1(chr14:69562099-81975384)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore BATF’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 248):

Position(s)	Effect	Δscore	Sites
14:75525082–75525083	acceptor_loss	1.0000	6
14:75525189–75525190	donor_loss	1.0000	3
14:75546460–75546461	acceptor_loss	1.0000	6
14:75522746–75522747	donor_loss	0.9900	3
14:75525190	donor_loss	0.9900
14:75522747	donor_loss	0.9800
14:75525189	donor_loss	0.9800
14:75546459	acceptor_gain	0.9700
14:75522746	donor_loss	0.9600
14:75546453	acceptor_gain	0.9500

AlphaMissense

344 missense substitutions predicted likely pathogenic (of 824 scored), across 79 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N36	8	0.998	1.000
D52	8	0.996	0.999
H55	8	0.995	1.000
H89	8	0.995	0.998
N65	8	0.993	0.998
S43	8	0.959	0.999
S58	8	0.849	0.995
C93	7	0.993	0.997
Q47	7	0.984	0.999
R33	7	0.983	1.000
R32	7	0.979	0.999
E62	7	0.971	0.991
E34	7	0.966	0.989
R46	7	0.938	0.999
Q41	7	0.927	0.999
E59	7	0.911	0.960
E57	7	0.907	0.980
F82	7	0.827	0.969
R37	6	0.999	1.000
K42	6	0.995	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	0.000103
Breast Invasive Carcinoma (TCGA)	favorable	0.000638

Disease associations

OMIM: gene MIM:612476 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST009597_37	Multiple sclerosis	6e-13
GCST005038_123	Allergic disease (asthma, hay fever or eczema)	9e-9
GCST001198_5	Multiple sclerosis	2e-8
GCST009617_1	LDL cholesterol levels x thiazide or thiazide-like diuretics use interaction	1e-7
GCST005531_84	Multiple sclerosis	2e-7

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Nickel	increases expression	2
TL8-506	affects cotreatment, increases expression	1
octa-2,4,6-trienoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
abrine	increases expression	1
LG 100815	increases expression	1
gardiquimod	increases expression, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Clodronic Acid	decreases expression	1
Ozone	increases expression	1
Selenium	increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression, increases abundance	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression	1
Vincristine	increases expression	1
Vitamin E	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Antirheumatic Agents	decreases expression	1
Palmitic Acid	decreases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0G9	SEES3-1V human BATF, clone1	Embryonic stem cell	Male
CVCL_A0H0	SEES3-1V human BATF, clone2	Embryonic stem cell	Male
CVCL_A0H1	SEES3-1V human BATF, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.