GABPB1

Summary

GABPB1 (GA binding protein transcription factor subunit beta 1, HGNC:4074) is a protein-coding gene on chromosome 15q21.2, encoding GA-binding protein subunit beta-1 (Q06547). Transcription factor capable of interacting with purine rich repeats (GA repeats).

This gene encodes the GA-binding protein transcription factor, beta subunit. This protein forms a tetrameric complex with the alpha subunit, and stimulates transcription of target genes. The encoded protein may be involved in activation of cytochrome oxidase expression and nuclear control of mitochondrial function. The crystal structure of a similar protein in mouse has been resolved as a ternary protein complex. Multiple transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 2553 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_016654

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4074
Approved symbol	GABPB1
Name	GA binding protein transcription factor subunit beta 1
Location	15q21.2
Locus type	gene with protein product
Status	Approved
Aliases	E4TF1-47, GABPB
Ensembl gene	ENSG00000104064
Ensembl biotype	protein_coding
OMIM	600610
Entrez	2553

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 38 protein_coding, 1 retained_intron

ENST00000220429, ENST00000359031, ENST00000380877, ENST00000396464, ENST00000429662, ENST00000543881, ENST00000558335, ENST00000558970, ENST00000559100, ENST00000560825, ENST00000561010, ENST00000901073, ENST00000901074, ENST00000901075, ENST00000901076, ENST00000901077, ENST00000901078, ENST00000901079, ENST00000901080, ENST00000901081, ENST00000901082, ENST00000901083, ENST00000901084, ENST00000928383, ENST00000928384, ENST00000946503, ENST00000946504, ENST00000946505, ENST00000946506, ENST00000946507, ENST00000946508, ENST00000946509, ENST00000946510, ENST00000946511, ENST00000946512, ENST00000946513, ENST00000946514, ENST00000946515, ENST00000946516

RefSeq mRNA: 7 — MANE Select: NM_016654 NM_001320910, NM_001320915, NM_002041, NM_005254, NM_016654, NM_016655, NM_181427

CCDS: CCDS10135, CCDS10136, CCDS32239, CCDS45258

Canonical transcript exons

ENST00000380877 — 9 exons

Exon	Start	End
ENSE00000688187	50302929	50303123
ENSE00000884611	50286068	50286183
ENSE00000884613	50289483	50289668
ENSE00000884614	50300789	50300902
ENSE00001377588	50301257	50301368
ENSE00001845346	50275389	50278784
ENSE00001929390	50354985	50355198
ENSE00003540625	50303966	50304133
ENSE00003758365	50309691	50309798

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 93.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1797 / max 190.5001, expressed in 1795 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149862	8.1734	1705
149864	4.4154	1676
149863	1.5909	1106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.76	gold quality
oocyte	CL:0000023	93.32	gold quality
cartilage tissue	UBERON:0002418	88.59	gold quality
bone marrow cell	CL:0002092	88.58	gold quality
bone marrow	UBERON:0002371	88.31	gold quality
ventricular zone	UBERON:0003053	88.01	gold quality
ganglionic eminence	UBERON:0004023	87.77	gold quality
calcaneal tendon	UBERON:0003701	87.37	gold quality
embryo	UBERON:0000922	86.70	gold quality
sperm	CL:0000019	86.30	silver quality
stromal cell of endometrium	CL:0002255	85.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.24	gold quality
mammary duct	UBERON:0001765	85.24	gold quality
buccal mucosa cell	CL:0002336	85.06	gold quality
epithelium of mammary gland	UBERON:0003244	85.04	gold quality
choroid plexus epithelium	UBERON:0003911	84.91	gold quality
corpus epididymis	UBERON:0004359	84.71	gold quality
adrenal tissue	UBERON:0018303	84.45	gold quality
monocyte	CL:0000576	84.06	gold quality
cauda epididymis	UBERON:0004360	84.03	gold quality
rectum	UBERON:0001052	83.97	gold quality
leukocyte	CL:0000738	83.95	gold quality
colonic epithelium	UBERON:0000397	83.95	gold quality
lymph node	UBERON:0000029	83.90	gold quality
mononuclear cell	CL:0000842	83.88	gold quality
caput epididymis	UBERON:0004358	83.79	gold quality
cortical plate	UBERON:0005343	83.73	gold quality
pericardium	UBERON:0002407	83.57	gold quality
male germ cell	CL:0000015	83.22	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	315.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
IL16	Activation
OXTR	Unknown

miRNA regulators (miRDB)

141 targeting GABPB1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548N	99.98	71.94	4170
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
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 19)

• Mutation of a nuclear respiratory factor 2 binding site in the 5’ untranslated region of the ADSL gene in three patients with adenylosuccinate lyase deficiency. (PMID:12016589)
• Results point out that brain-specific angiogenesis inhibitor 2 controls VEGF transcription through GA-binding protein under normal conditions and cerebral ischemia [GA-binding protein gamma]. (PMID:16412436)
• serum-responsive GABP binding to Ets-binding sites activates the KIS promoter, leading to KIS gene expression, cell migration, and cell cycle progression (PMID:17726090)
• The results are consistent with a pathway whereby PRC regulates NRF-2-dependent genes through a multiprotein complex involving HCF-1.[NRF-2beta] (PMID:18343819)
• Data show that BRAF knockdown led to suppression of the expression of the GABPbeta, which involved in regulating HPR1 promoter activity. (PMID:21076620)
• NRF-1 and GABP expression is coordinated by NRF-1’s activation of the GABPbeta promoter (PMID:21609478)
• GABP beta is required for YAP expression in vitro and in vivo, and that YAP is an important effector downstream of GABP for cell survival and cell-cycle progression. (PMID:23684612)
• The NRF-2beta nuclear localization signal (NLS) is an unusual but is, nevertheless, a bona fide monopartite-type NLS. (PMID:23856623)
• Ectopic overexpression of a dominant-negative acting GABP mutant led to impaired myeloid differentiation of CD34(+) hematopoietic stem/progenitor cells. (PMID:27100840)
• role for GABPA/B1 as the critical ETS transcription factors deregulating SDHD expression in the context of highly recurrent promoter mutations in melanoma. (PMID:28108517)
• Data revealed high expression of GABPB1 in clear cell renal cell carcinoma (ccRCC) tissues and cell lines. Its knockdown significantly decreased the colony formation ability via induction of p21Waf/Cip1 expression. Furthermore, the patients at high risk of a poor survival outcome exhibited the highest expression level of GABPB1. These findings imply that GABPB1 serves an important role in the progression of ccRCC. (PMID:29845229)
• Study in glioblastoma cells shows that genetic disruption of GABPbeta1L (beta1L), a tetramer-forming isoform of GABP that is dispensable for normal development, results in TERT silencing in a TERT promoter mutation-dependent manner. Reducing TERT expression by disrupting beta1L culminates in telomere loss and cell death exclusively in TERT promoter mutant cells. (PMID:30205050)
• G allele of (rs7181866 A/G) was found to be significantly associated with risk for obesity among T2DM subjects (PMID:30904536)
• LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells. (PMID:31700067)
• FGFR4 promotes nuclear localization of GABP to inhibit cell apoptosis in uterine leiomyosarcoma. (PMID:33151453)
• Association study of performance-related polymorphisms in Brazilian combat-sport athletes highlights variants in the GABPB1 gene. (PMID:33346691)
• Cancer-specific loss of TERT activation sensitizes glioblastoma to DNA damage. (PMID:33758097)
• Association of single nucleotide polymorphisms in the nuclear respiratory factor-2 beta subunit-encoding the GABPB1 gene within the occupational environment. (PMID:35343317)
• The cyrstal structure of a ternary complex containing the mouse GA binding protein transcription factor, beta subunit 2, was resolved at 2.15 angstrom resolution. (PMID:9461436)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabpb1	ENSDARG00000023659
mus_musculus	Gabpb1	ENSMUSG00000027361
rattus_norvegicus	Gabpb1	ENSRNOG00000010659
rattus_norvegicus	Gabpb1l	ENSRNOG00000053439

Paralogs (2): GABPB2 (ENSG00000143458), IQANK1 (ENSG00000203499)

Protein

Protein identifiers

GA-binding protein subunit beta-1 — Q06547 (reviewed: Q06547)

Alternative names: GABP subunit beta-2, Nuclear respiratory factor 2, Transcription factor E4TF1-47, Transcription factor E4TF1-53

All UniProt accessions (5): Q06547, F5H7I4, H0YMZ5, H0YNZ0, H9ZYI9

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor capable of interacting with purine rich repeats (GA repeats). Acts as a master regulator of nuclear-encoded mitochondrial genes. (Microbial infection) Necessary for the expression of the Adenovirus E4 gene.

Subunit / interactions. Heterotetramer of two alpha and two beta subunits. Interacts with HCFC1, causing repression of transcriptional activity.

Subcellular location. Nucleus.

Post-translational modifications. Acetylated by EP300/p300. Deacetylated by SIRT7, promoting heterotetramerization and activity.

Isoforms (4)

UniProt ID	Names	Canonical?
Q06547-1	1, GABPB-1, Beta-1	yes
Q06547-2	2, Beta-2
Q06547-3	3, GABPB-2, Gamma-1
Q06547-4	4, Gamma-2

RefSeq proteins (7): NP_001307839, NP_001307844, NP_002032, NP_005245, NP_057738, NP_057739, NP_852092 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR050663	Ankyrin-SOCS_Box	Family

Pfam: PF00023, PF12796

UniProt features (27 total): mutagenesis site 8, repeat 5, modified residue 4, sequence conflict 4, splice variant 2, initiator methionine 1, chain 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06547-F1	69.46	0.48

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): 352, 381, 2, 69

Mutagenesis-validated functional residues (8):

Position	Phenotype
262–263	minor reduction in transcriptional activation; when associated with a-295 or a-305 and a-306.
264–265	minor effect upon interaction with hcfc1 and transcriptional activation. loss of activity; when associated with a-297; a
270–271	minor reduction in transcriptional activation. moderate reduction in activity; when associated with a-305 and a-306.
273–275	strongly reduces interaction with hcfc1 and transcriptional activation. loss of activity; when associated with a-297; a-
295	no effect on transcriptional activation. minor reduction in activity; when associated with a-270 and a-271.
297–299	strongly reduces interaction with hcfc1 and transcriptional activation. loss of activity; when associated with a-264 and
305–306	minor reduction in transcriptional activation. moderate reduction in activity; when associated with a-270 and a-271.
307–310	moderately reduces interaction with hcfc1 and transcriptional activation. loss of activity; when associated with a-273 a

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis

MSigDB gene sets: 389 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, SWEET_KRAS_ONCOGENIC_SIGNATURE, AAGCCAT_MIR135A_MIR135B, MAZ_Q6, IVANOVA_HEMATOPOIESIS_MATURE_CELL, CAGCTG_AP4_Q5, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_48HR_DN, MODULE_331, NFKB_C, HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP, BOYLAN_MULTIPLE_MYELOMA_C_CLUSTER_UP, ATTCTTT_MIR186, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, ATGCTGG_MIR338

GO Biological Process (2): mitochondrion organization (GO:0007005), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (2): transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasmic ribonucleoprotein granule (GO:0036464)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitochondrial biogenesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
ribonucleoprotein granule	1

Protein interactions and networks

STRING

1565 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABPB1	GABPA	Q06546	999
GABPB1	TFAM	Q00059	928
GABPB1	YAF2	Q8IY57	864
GABPB1	PPARGC1A	Q9UBK2	859
GABPB1	TFB1M	Q8WVM0	852
GABPB1	RYBP	Q8N488	829
GABPB1	YY1	P25490	811
GABPB1	TFB2M	Q9H5Q4	698
GABPB1	NRF1	Q16656	697
GABPB1	ESRRA	P11474	661
GABPB1	POLRMT	O00411	639
GABPB1	CBX2	Q14781	583
GABPB1	KLK6	Q92876	556
GABPB1	HNF1A	P20823	480
GABPB1	RING1	Q06587	445

IntAct

89 interactions, top by confidence:

A	B	Type	Score
TRAF2	GABPB1	psi-mi:“MI:0915”(physical association)	0.780
GABPB1	TRAF2	psi-mi:“MI:0915”(physical association)	0.780
TDRD7	GABPB1	psi-mi:“MI:0915”(physical association)	0.740
GABPB1	TDRD7	psi-mi:“MI:0915”(physical association)	0.740
LMO4	GABPB1	psi-mi:“MI:0915”(physical association)	0.720
GABPB1	LMO4	psi-mi:“MI:0915”(physical association)	0.720
GABPA	GABPB1	psi-mi:“MI:0915”(physical association)	0.700
GABPB1	GABPA	psi-mi:“MI:0915”(physical association)	0.700
GABPA	GABPB1	psi-mi:“MI:0914”(association)	0.700
GABPB1	LMO1	psi-mi:“MI:0915”(physical association)	0.670
LMO1	GABPB1	psi-mi:“MI:0915”(physical association)	0.670
GABPB1	MAGEB18	psi-mi:“MI:0915”(physical association)	0.620
Adgrb2	GABPB1	psi-mi:“MI:0915”(physical association)	0.580
Adgrb2	GABPB1	psi-mi:“MI:0407”(direct interaction)	0.580
SNRPB2	GABPB1	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	SNRPA	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	RBM11	psi-mi:“MI:0915”(physical association)	0.560
POGZ	GABPB1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (71): LMO1 (Two-hybrid), SNRPA (Two-hybrid), SNRPB2 (Two-hybrid), TRAF2 (Two-hybrid), LMO4 (Two-hybrid), POGZ (Two-hybrid), TDRD7 (Two-hybrid), RSPH14 (Two-hybrid), RBM11 (Two-hybrid), FAM90A1 (Two-hybrid), GABPB1 (Two-hybrid), TPD52L2 (Affinity Capture-MS), GABPA (Affinity Capture-MS), TDRD7 (Affinity Capture-MS), GABPB1 (Two-hybrid)

ESM2 similar proteins: A6QQW0, B4F7E9, O15391, O43167, O62836, O70230, O70494, P08048, P15337, P17010, P17012, P18846, P20385, P25490, P27699, P36508, P52747, P79145, P81069, P81269, Q00420, Q00899, Q01147, Q01611, Q02447, Q03060, Q03061, Q06547, Q08DA8, Q0V8G2, Q1LYE3, Q1LZH5, Q1RMI3, Q4V8R6, Q52KB5, Q52V16, Q58DZ6, Q5XIU2, Q66K89, Q6B4Z5

Diamond homologs: P81069, Q00420, Q06547, Q0V8G2, Q1RMI3, Q69ZU8, Q8TAK5, Q9Y2G4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GABPB1	“down-regulates activity”	HCFC1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2484 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:50303032:A:G	L123S	1.000
15:50303080:G:T	A107D	1.000
15:50303098:T:A	D101V	1.000
15:50303098:T:G	D101A	1.000
15:50303099:C:G	D101H	1.000
15:50303973:A:G	L90S	1.000
15:50304006:G:T	A79D	1.000
15:50304010:C:G	A78P	1.000
15:50304021:G:C	P74R	1.000
15:50304021:G:T	P74Q	1.000
15:50304027:C:G	R72P	1.000
15:50304069:A:G	L58P	1.000
15:50304072:A:G	L57P	1.000
15:50304096:C:A	G49V	1.000
15:50304111:A:G	L44P	1.000
15:50304117:A:T	L42H	1.000
15:50304120:G:T	P41Q	1.000
15:50304129:C:A	G38V	1.000
15:50304129:C:T	G38E	1.000
15:50304130:C:G	G38R	1.000
15:50304130:C:T	G38R	1.000
15:50309695:T:A	D35V	1.000
15:50302998:A:C	S134R	0.999
15:50302998:A:T	S134R	0.999
15:50303000:T:G	S134R	0.999
15:50303068:G:T	A111D	0.999
15:50303069:C:G	A111P	0.999
15:50303070:C:A	W110C	0.999
15:50303070:C:G	W110C	0.999
15:50303072:A:G	W110R	0.999

dbSNP variants (sampled 300 via entrez): RS1000005840 (15:50297162 C>A,T), RS1000014871 (15:50318181 A>G), RS1000030194 (15:50324914 A>T), RS1000046809 (15:50357111 C>T), RS1000089863 (15:50319665 G>A,T), RS1000145923 (15:50324644 A>G), RS1000200355 (15:50280410 T>C), RS1000220475 (15:50287713 T>C), RS1000232892 (15:50283049 T>C), RS1000236927 (15:50304480 G>T), RS1000256345 (15:50331022 C>T), RS1000303671 (15:50328384 A>T), RS1000323103 (15:50317684 T>C,G), RS1000330850 (15:50337483 G>T), RS1000357170 (15:50285532 G>A)

Disease associations

OMIM: gene MIM:600610 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
trichostatin A	affects expression, decreases expression	2
sodium arsenite	increases abundance, increases expression	2
Cisplatin	affects expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases abundance, increases expression	1
butylbenzyl phthalate	decreases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression	1
seocalcitol	decreases expression	1
deguelin	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Antimycin A	increases expression	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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