GABPA

Summary

GABPA (GA binding protein transcription factor subunit alpha, HGNC:4071) is a protein-coding gene on chromosome 21q21.3, encoding GA-binding protein alpha chain (Q06546). Transcription factor capable of interacting with purine rich repeats (GA repeats). It is a selective cancer dependency (DepMap: 81.9% of cell lines).

This gene encodes one of three GA-binding protein transcription factor subunits which functions as a DNA-binding subunit. Since this subunit shares identity with a subunit encoding the nuclear respiratory factor 2 gene, it is likely involved in activation of cytochrome oxidase expression and nuclear control of mitochondrial function. This subunit also shares identity with a subunit constituting the transcription factor E4TF1, responsible for expression of the adenovirus E4 gene. Because of its chromosomal localization and ability to form heterodimers with other polypeptides, this gene may play a role in the Down Syndrome phenotype. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 2551 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 44 total — 1 pathogenic
• Phenotypes (HPO): 1
• Cancer dependency (DepMap): dependent in 81.9% of screened cell lines
• Transcription factor: yes — 53 downstream targets (CollecTRI)
• MANE Select transcript: NM_002040

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4071
Approved symbol	GABPA
Name	GA binding protein transcription factor subunit alpha
Location	21q21.3
Locus type	gene with protein product
Status	Approved
Aliases	E4TF1A, NFT2, NRF2, E4TF1-60, NRF2A
Ensembl gene	ENSG00000154727
Ensembl biotype	protein_coding
OMIM	600609
Entrez	2551

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 36 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000354828, ENST00000400075, ENST00000487266, ENST00000904127, ENST00000904128, ENST00000904129, ENST00000904130, ENST00000904131, ENST00000904132, ENST00000904133, ENST00000904134, ENST00000904135, ENST00000904136, ENST00000904137, ENST00000904138, ENST00000904139, ENST00000924592, ENST00000924593, ENST00000924594, ENST00000924595, ENST00000924596, ENST00000924597, ENST00000924598, ENST00000924599, ENST00000924600, ENST00000924601, ENST00000924602, ENST00000924603, ENST00000924604, ENST00000962271, ENST00000962272, ENST00000962273, ENST00000962274, ENST00000962275, ENST00000962276, ENST00000962277, ENST00000962278

RefSeq mRNA: 2 — MANE Select: NM_002040 NM_001197297, NM_002040

CCDS: CCDS13575

Canonical transcript exons

ENST00000400075 — 10 exons

Exon	Start	End
ENSE00001017318	25741573	25741675
ENSE00001017320	25764210	25764350
ENSE00001017321	25764595	25764787
ENSE00001017322	25758010	25758204
ENSE00001017324	25751989	25752234
ENSE00001017326	25762312	25762365
ENSE00001411573	25769004	25772460
ENSE00001879843	25734972	25735578
ENSE00003647582	25749036	25749120
ENSE00003678494	25745210	25745354

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 94.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2355 / max 271.3708, expressed in 1788 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188669	5.8822	1617
188671	3.5025	1464
188672	3.3831	1427
188673	2.4677	1232

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.44	gold quality
ventricular zone	UBERON:0003053	89.24	gold quality
ganglionic eminence	UBERON:0004023	88.76	gold quality
thymus	UBERON:0002370	88.73	gold quality
upper arm skin	UBERON:0004263	88.33	gold quality
layer of synovial tissue	UBERON:0007616	88.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.83	gold quality
smooth muscle tissue	UBERON:0001135	87.77	gold quality
cortical plate	UBERON:0005343	86.96	gold quality
oviduct epithelium	UBERON:0004804	86.65	gold quality
synovial joint	UBERON:0002217	86.56	gold quality
germinal epithelium of ovary	UBERON:0001304	86.53	gold quality
lymph node	UBERON:0000029	86.25	gold quality
mammary duct	UBERON:0001765	86.19	gold quality
monocyte	CL:0000576	86.10	gold quality
leukocyte	CL:0000738	86.08	gold quality
epithelium of mammary gland	UBERON:0003244	85.94	gold quality
rectum	UBERON:0001052	85.92	gold quality
decidua	UBERON:0002450	85.79	gold quality
adrenal tissue	UBERON:0018303	85.76	gold quality
endometrium	UBERON:0001295	85.22	gold quality
gall bladder	UBERON:0002110	85.19	gold quality
epithelial cell of pancreas	CL:0000083	85.18	silver quality
vermiform appendix	UBERON:0001154	85.15	gold quality
cardiac muscle of right atrium	UBERON:0003379	84.95	silver quality
islet of Langerhans	UBERON:0000006	84.89	gold quality
tibialis anterior	UBERON:0001385	84.84	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.63	gold quality
tendon	UBERON:0000043	84.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.44	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	408.23
E-CURD-112	yes	4.96
E-GEOD-124858	no	215.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

53 targets.

Target	Regulation
ABCC1	Unknown
ACHE	Activation
ADAM2
AR
ATP5F1B	Activation
AURKA	Activation
BRCA1	Activation
CD79A	Activation
CHRND	Activation
CHRNE	Activation
COX4I1	Activation
CYP2B6
CYP7B1
DLD	Activation
ELANE	Activation
ERBB2	Unknown
F9	Unknown
GFI1
GFM1
HGS
IL10	Activation
IL16	Activation
IL2
IL2RB	Activation
IL7R	Unknown
ITGB2	Activation
LIG4	Activation
NOTCH1
OXTR	Unknown
POLA1	Activation

JASPAR motifs

Motif	Name	Family
MA0062.1	GABPA	Ets-related
MA0062.3	GABPA	Ets-related
MA0062.4	GABPA	Ets-related

JASPAR matrix evidence (PMIDs): PMID:8383622, PMID:9461436

Upstream regulators (CollecTRI, top): ATF1, CREB1, E2F4, ETS1, SP1, STAT3

miRNA regulators (miRDB)

242 targeting GABPA, 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-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 81.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• GABP is essential for the regulation of IL-7Ralpha expression in T cells. (PMID:15361867)
• there is a physical interaction between the GABPalpha subunit and C/EBPalpha (PMID:15928042)
• TRAP220/MED1 plays a novel coregulatory role in facilitating the recruitment of TRAP/Mediator to specific target genes involved in growth and cell cycle progression via GABP (PMID:16574658)
• GABPA and p300 are essential components of retinoic acid-induced enhanceosome in myeloid cells. (PMID:16581781)
• NRF-2 may play a key role in the regulation of mitochondrial protein synthesis in a cell line. (PMID:17161026)
• Upon activation of AChR, GABP recruits the histone acetyl transferase (HAT) p300 on the AChR epsilon subunit promoter, whereas it rather recruits the histone deacetylase HDAC1 when the promoter is not activated. (PMID:17304221)
• These findings demonstrate that GABP regulates the majority of divergent promoters and suggest that bidirectional transcriptional activity is mediated through GABP binding and transactivation at both divergent and nondivergent promoters. (PMID:18020712)
• Elf-1 in combination with Sp1 and GABP reduced FcRgamma promoter activity. (PMID:18378679)
• nuclear respiratory factor-2 binding site methylation suppresses the promoter activity of the human TOMM70 gene (PMID:18852034)
• ILF-3, which has been known to regulate IL-2 expression in T cells, up-regulates synoviolin expression with GABPalpha in rheumatoid synovial cells (PMID:19116932)
• study identified a decrease in a transcription factor complex containing NRF-2 in nuclear extracts from multiple sclerosis cortex; decrease correlates with decreased expression of electron transport chain subunit genes & increased oxidative damage (PMID:19187944)
• The intronic DNase I-hypersensitive sites element acts in cis to maintain transcriptional competency at the TMS1 locus and that this activity is mediated by the ets transcription factor, GABPalpha. (PMID:19324871)
• Data show that a significant overlaps between the ELK1- and SRF-binding regions, and between ELK1- and GABPA-binding regions. (PMID:19687146)
• Data show that NRF2 binds to the proximal promoter region of the genes coding for the mTERF, POLRMT, the B subunit of the DNA polymerase-gamma, TWINKLE, and the single-stranded DNA-binding protein mtSSB. (PMID:19951946)
• NRF2 A/C and NRF2 C/T single nucleotide polymorphisms (SNPs) are associated, separately and in combination, with elite endurance athletes. (PMID:20028934)
• expression of NRF-2alpha in hepatocellular carcinoma (HCC) and tumor-adjacent specimens; higher-grade frequency of expression of NRF-2alpha in tumor-adjacent tissues was higher than tumor tissues, suggesting NRF-2alpha may play important role in carcinogenesis of HCC (PMID:20127517)
• Hepatoprotection of quercetin against oxidative stress by induction of metallothionein expression through activating MAPK and PI3K pathways and enhancing Nrf2 DNA-binding activity. (PMID:21624509)
• an Nrf2-dependent response to exogenous stimuli may affect annual FEV1 decline (PMID:21774808)
• Results suggest that the NRF-2 A/C polymorphism is associated with endurance performance at the elite level in a Spanish population. (PMID:22749526)
• The phenotype is best uniformly termed congenital cone-rod synaptic disorder. In Saudi Arabia a founder homozygous c.81_82insA CABP4 mutation is a recurrent cause. (PMID:23099293)
• although ELK1 and GABPA ultimately control the same biological process, they do so by regulating different cohorts of target genes associated with cytoskeletal functions and cell migration contro (PMID:23284628)
• GABP alpha 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)
• When NRF-2alpha and NRF-2beta form a complex, the nuclear import of NRF-2alphabeta becomes strictly dependent on the nuclear localization signal within NRF-2beta. (PMID:23856623)
• results demonstrate the functional importance of the C/EBPalpha C-terminus beyond the bZIP DNA-binding and dimerization region, which may mediate cooperative activation by C/EBPalpha and GABP of myeloid-specific genes (PMID:24076158)
• GABPA exhibits an increase in binding signal with higher numbers of ETS motifs per promoter. Analysis of the distance between inverted pairs of ETS motifs within promoters and binding by p53, ETS1 and GABPA, shows a coordination of binding for the 3. (PMID:24481480)
• GABPA thus directly links TERT promoter mutations to aberrant expression in multiple cancers. (PMID:25977370)
• Expression of the ETS transcription factor GABPalpha is positively correlated to the BCR-ABL1/ABL1 ratio in CML patients and affects imatinib sensitivity in vitro. (PMID:26072332)
• The results suggest that NRF-2alpha is a regulator of SIRT3 expression and may shed light on how SIRT3 is upregulated during nutrient stress. (PMID:26109058)
• study supports the crucial role of GABP in myeloid cell differentiation and identified ITGAM/CD11b as a novel GABP target gene (PMID:26170143)
• GABPalpha Binding to Overlapping ETS and CRE DNA Motifs Is Enhanced by CREB1 (PMID:26185160)
• ELF1 binding occurs at both TERT promoter mutations in melanoma in vitro such that increased recruitment of GABP is enabled by the spatial architecture of native and novel ETS motifs in the TERT promoter region. (PMID:26553150)
• Analyses of data sets link GABPa to cognitive disorders, diabetes, KRAB zinc finger (KRAB-ZNF), and human-specific genes. (PMID:26814189)
• CRISPR-mediated reversal of mutant TERT promoters, or deletion of its long-range interacting chromatin, abrogates GABPA binding and long-range interactions, leading to depletion of active histone marks, loss of POL2 recruitment, and suppression of TERT transcription (PMID:27650951)
• potential mechanism of TERT reactivation mediated by a novel long-range chromatin interaction between the TERT promoter on chromosome 5p and a 300-kb upstream region. This permits recruitment of the transcription factor GABPA in mutant TERT promoters but not in wild-type promoters. (PMID:27807101)
• a key 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)
• Collectively, our data indicate that GABPA inhibits hepatocellular carcinoma cell migration and could serve as a novel biomarker for prognosis (PMID:28549418)
• enhanced ETS factor activity and the transcription of ETS family target genes related to spliceosome function and cell death induction via alternate MCL1 splicing, is reported. (PMID:29118074)
• Data indicate the essential role of the GABP transcription factor in activating translocase of inner mitochondrial membrane 23 TIMM23 and TIMM23B expression. (PMID:29413900)
• a positive correlation between GABPA and DICER1 expression was seen in multiple types of malignancies. Taken together, despite its stimulatory effect on the mutant TERT promoter and telomerase activation, GABPA may itself act as a tumor suppressor rather than an oncogenic factor to inhibit invasion/metastasis in thyroid carcinomas. (PMID:30181547)
• Therefore, we proposed that GABPA cooperates with the states of histone acetylation to act as a novel bookmarking factor which, may negatively regulate transcription during the early G1 phase. (PMID:30836589)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gabpa	ENSDARG00000069289
mus_musculus	Gabpa	ENSMUSG00000008976
rattus_norvegicus	Gabpa	ENSRNOG00000053205
drosophila_melanogaster	Ets97D	FBGN0004510

Paralogs (28): ETV1 (ENSG00000006468), ETV7 (ENSG00000010030), SPI1 (ENSG00000066336), ELF4 (ENSG00000102034), ETV2 (ENSG00000105672), ERF (ENSG00000105722), ELF2 (ENSG00000109381), ELK3 (ENSG00000111145), ETV3 (ENSG00000117036), ELF1 (ENSG00000120690), SPDEF (ENSG00000124664), ELK1 (ENSG00000126767), ETS1 (ENSG00000134954), EHF (ENSG00000135373), ELF5 (ENSG00000135374), ETV6 (ENSG00000139083), FLI1 (ENSG00000151702), ERG (ENSG00000157554), ETS2 (ENSG00000157557), ELK4 (ENSG00000158711), ELF3 (ENSG00000163435), FEV (ENSG00000163497), SPIC (ENSG00000166211), ETV4 (ENSG00000175832), ETV5 (ENSG00000244405), ETV3L (ENSG00000253831), ERFL (ENSG00000268041), SPIB (ENSG00000269404)

Protein

Protein identifiers

GA-binding protein alpha chain — Q06546 (reviewed: Q06546)

Alternative names: Nuclear respiratory factor 2 subunit alpha, Transcription factor E4TF1-60

All UniProt accessions (2): Q06546, A8IE48

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor capable of interacting with purine rich repeats (GA repeats). Positively regulates transcription of transcriptional repressor RHIT/ZNF205. (Microbial infection) Necessary for the expression of the Adenovirus E4 gene.

Subunit / interactions. Heterotetramer of two alpha and two beta subunits.

Subcellular location. Nucleus.

Similarity. Belongs to the ETS family.

RefSeq proteins (2): NP_001184226, NP_002031* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000418	Ets_dom	Domain
IPR003118	Pointed_dom	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR016312	TF_GA-bd_asu	Family
IPR024668	GABP_asu_N	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR046328	ETS_fam	Family

Pfam: PF00178, PF02198, PF11620

UniProt features (9 total): sequence variant 2, sequence conflict 2, chain 1, domain 1, DNA-binding region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06546-F1	68.86	0.26

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 (1): 303

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 268 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BROWNE_HCMV_INFECTION_8HR_UP, ATACCTC_MIR202, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, GOBP_BLASTOCYST_FORMATION, ATGTTAA_MIR302C, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MEGAKARYOCYTE_DIFFERENTIATION

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), blastocyst formation (GO:0001825), regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), negative regulation of megakaryocyte differentiation (GO:0045653), positive regulation of transcription by RNA polymerase II (GO:0045944), in utero embryonic development (GO:0001701), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (10): transcription cis-regulatory region binding (GO:0000976), 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), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

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
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
blastocyst development	1
anatomical structure formation involved in morphogenesis	1
cellular developmental process	1
megakaryocyte differentiation	1
negative regulation of myeloid cell differentiation	1
regulation of megakaryocyte differentiation	1
positive regulation of DNA-templated transcription	1
chordate embryonic development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
DNA binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GABPA	GABPB1	Q06547	999
GABPA	TFAM	Q00059	866
GABPA	METTL23	Q86XA0	788
GABPA	YY1	P25490	777
GABPA	COX6A1	P12074	773
GABPA	NRF1	Q16656	768
GABPA	CTCF	P49711	723
GABPA	ESRRA	P11474	686
GABPA	PPARGC1A	Q9UBK2	679
GABPA	PPARGC1B	Q86YN6	675
GABPA	YAF2	Q8IY57	656
GABPA	ELF1	P32519	635
GABPA	MYC	P01106	582
GABPA	CREB1	P16220	578
GABPA	SIN3A	Q96ST3	560

IntAct

90 interactions, top by confidence:

A	B	Type	Score
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
GABPB2	GABPA	psi-mi:“MI:0915”(physical association)	0.770
GABPA	GABPB2	psi-mi:“MI:0915”(physical association)	0.770
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
FHL2	GABPA	psi-mi:“MI:0407”(direct interaction)	0.590
GABPA	ZC2HC1B	psi-mi:“MI:0915”(physical association)	0.560
STK16	GABPA	psi-mi:“MI:0915”(physical association)	0.560
SP1	GABPA	psi-mi:“MI:0407”(direct interaction)	0.540
SP3	GABPA	psi-mi:“MI:0407”(direct interaction)	0.540
SP1	GABPA	psi-mi:“MI:0915”(physical association)	0.540
GABPA	SP3	psi-mi:“MI:0915”(physical association)	0.540
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
TPD52L3	TPD52L2	psi-mi:“MI:0914”(association)	0.530
YEATS4	ACTL6B	psi-mi:“MI:0914”(association)	0.530
HCFC1	GABPA	psi-mi:“MI:0915”(physical association)	0.500
HCFC1	GABPA	psi-mi:“MI:0914”(association)	0.500
ADGRB2	GABPA	psi-mi:“MI:0915”(physical association)	0.400
	GABPA	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (165): EP300 (Affinity Capture-Western), EP300 (Reconstituted Complex), GABPA (Reconstituted Complex), GABPA (Affinity Capture-Western), GABPA (Affinity Capture-MS), GABPA (Affinity Capture-MS), GABPA (Co-fractionation), GABPA (Affinity Capture-MS), GABPA (Two-hybrid), GABPA (Affinity Capture-MS), GABPA (Affinity Capture-MS), GABPA (Affinity Capture-MS), GABPA (Affinity Capture-MS), GABPA (Affinity Capture-MS), GABPA (Reconstituted Complex)

ESM2 similar proteins: A2VDZ4, A5PKL1, A7KAX9, A8KBE0, B2GUY1, B3LXF2, B4F6Q9, E2QYC9, E7F1U2, E7FDW2, F1MAD2, O15018, O55164, O75970, P68907, Q00422, Q06546, Q4L1J4, Q63ZW7, Q64702, Q69ZS0, Q6AWC2, Q6DJR2, Q6IVY4, Q6NLL1, Q6RHR9, Q6XZF7, Q6ZMN7, Q7ZXT3, Q80VW5, Q810W9, Q8CDM1, Q8K3E5, Q8N573, Q8NI35, Q8VBX6, Q92870, Q96QZ7, Q99NH2, Q9BYG5

Diamond homologs: A0A1W2PQ73, A0JN51, A1A4L6, A1YF15, A1YG61, A1YG91, A2D4Z7, A2T737, A2T762, A3FEM2, A4GTP4, A8WFJ9, O00321, O01519, O70132, O70273, O95238, P01105, P10157, P11308, P11536, P13474, P14921, P15036, P15037, P15062, P18755, P18756, P19102, P19419, P20105, P26323, P27577, P28322, P28324, P29773, P29774, P29775, P29776, P32519

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	29
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1184625	Single allele	Pathogenic

SpliceAI

1884 predictions. Top by Δscore:

Variant	Effect	Δscore
21:25745208:A:AG	acceptor_gain	1.0000
21:25745209:G:GG	acceptor_gain	1.0000
21:25745209:GC:G	acceptor_gain	1.0000
21:25745209:GCA:G	acceptor_gain	1.0000
21:25745209:GCATT:G	acceptor_gain	1.0000
21:25745350:TCCAG:T	donor_loss	1.0000
21:25745351:CCAGG:C	donor_loss	1.0000
21:25745352:CAGG:C	donor_loss	1.0000
21:25745353:AGGTA:A	donor_loss	1.0000
21:25745354:GG:G	donor_loss	1.0000
21:25745355:G:C	donor_loss	1.0000
21:25745356:T:G	donor_loss	1.0000
21:25749028:AT:A	acceptor_gain	1.0000
21:25749029:T:TA	acceptor_gain	1.0000
21:25749030:G:A	acceptor_gain	1.0000
21:25749034:A:AG	acceptor_gain	1.0000
21:25749034:AGCT:A	acceptor_gain	1.0000
21:25749035:G:GG	acceptor_gain	1.0000
21:25749035:GCTG:G	acceptor_gain	1.0000
21:25751981:C:G	acceptor_gain	1.0000
21:25751982:T:A	acceptor_gain	1.0000
21:25751984:TTCAG:T	acceptor_loss	1.0000
21:25751986:CAGG:C	acceptor_loss	1.0000
21:25751987:A:AG	acceptor_gain	1.0000
21:25751987:AG:A	acceptor_gain	1.0000
21:25751987:AGGA:A	acceptor_loss	1.0000
21:25751988:G:GG	acceptor_gain	1.0000
21:25751988:GG:G	acceptor_gain	1.0000
21:25751988:GGA:G	acceptor_gain	1.0000
21:25752204:A:T	donor_gain	1.0000

AlphaMissense

2986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:25745341:T:C	L70P	1.000
21:25752177:T:A	W166R	1.000
21:25752177:T:C	W166R	1.000
21:25752178:G:C	W166S	1.000
21:25752179:G:C	W166C	1.000
21:25752179:G:T	W166C	1.000
21:25752211:A:C	Q177P	1.000
21:25752212:A:C	Q177H	1.000
21:25752212:A:T	Q177H	1.000
21:25758013:C:A	P186H	1.000
21:25758021:T:A	W189R	1.000
21:25758021:T:C	W189R	1.000
21:25758022:G:C	W189S	1.000
21:25758023:G:C	W189C	1.000
21:25758023:G:T	W189C	1.000
21:25758045:T:A	W197R	1.000
21:25758045:T:C	W197R	1.000
21:25758046:G:C	W197S	1.000
21:25758047:G:C	W197C	1.000
21:25758047:G:T	W197C	1.000
21:25758054:T:A	W200R	1.000
21:25758054:T:C	W200R	1.000
21:25758056:G:C	W200C	1.000
21:25758056:G:T	W200C	1.000
21:25758069:T:C	F205L	1.000
21:25758070:T:C	F205S	1.000
21:25758071:C:A	F205L	1.000
21:25758071:C:G	F205L	1.000
21:25758111:G:A	G219R	1.000
21:25758111:G:C	G219R	1.000

dbSNP variants (sampled 300 via entrez): RS1000047691 (21:25740314 G>A,C), RS1000253134 (21:25743245 C>CT), RS1000273514 (21:25734541 A>T), RS1000411806 (21:25740480 A>G), RS1000431249 (21:25768378 G>A,T), RS1000504002 (21:25740063 A>C,G), RS1000636597 (21:25765227 G>A), RS1000692298 (21:25751770 T>C,G), RS1000759107 (21:25758781 A>C), RS1000782457 (21:25768680 G>C), RS1000791966 (21:25758484 C>A), RS1000840282 (21:25745007 T>G), RS1000853786 (21:25744452 G>A), RS1000952241 (21:25751154 GATAA>G), RS1001004468 (21:25750747 GAAA>G)

Disease associations

OMIM: gene MIM:600609 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): Alzheimer disease (MONDO:0004975)

Orphanet (2): Early-onset autosomal dominant Alzheimer disease (Orphanet:1020), NON RARE IN EUROPE: Alzheimer disease (Orphanet:238616)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0002511	Alzheimer disease

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010105_52	Nicotine dependence symptom count	2.000000e-06
GCST010273_2	Gout (normal type)	7.000000e-08
GCST90011768_17	Glaucoma (primary open-angle)	7.000000e-06
GCST90011770_82	Glaucoma (primary open-angle)	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009262	nicotine dependence symptom count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000544	Alzheimer Disease	C10.228.140.380.100; C10.574.945.249; F03.615.400.100

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs59288687	GABPA		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
trichostatin A	affects cotreatment, decreases expression, affects expression	3
Air Pollutants	increases expression, affects cotreatment, increases abundance, increases oxidation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
butyraldehyde	decreases expression	1
2-tert-butylhydroquinone	affects localization	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
SB 203580	decreases reaction, increases expression	1
GW 7604	increases expression	1
pyrazolanthrone	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Caffeine	increases phosphorylation	1
Clorgyline	increases expression	1
Gallic Acid	increases expression, affects localization, increases activity, decreases reaction	1

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2E5	SEES3-1V human GABPA, clone1	Embryonic stem cell	Male
CVCL_A2E6	SEES3-1V human GABPA, clone2	Embryonic stem cell	Male
CVCL_A2E7	SEES3-1V human GABPA, clone3	Embryonic stem cell	Male
CVCL_GZ86	K562 eGFP-GABPA	Cancer cell line	Female
CVCL_HA14	MCF-7 eGFP-GABPA	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00009191	PHASE4	COMPLETED	The Depression in Alzheimer’s Disease Study (DIADS)
NCT00009217	PHASE4	COMPLETED	Treatment of Behavioral Symptoms in Alzheimer’s Disease
NCT00018278	PHASE4	COMPLETED	Electrophysiologic Measures of Treatment Response in Alzheimer Disease
NCT00035204	PHASE4	COMPLETED	A Study of the Effects on Sleep, Attention, and Gastrointestinal Tolerance of Galantamine and Donepezil in Patients With Alzheimer’s Disease
NCT00042172	PHASE4	COMPLETED	Treatment for Early Memory Loss
NCT00046358	PHASE4	COMPLETED	The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated With Alzheimer’s Disease
NCT00104442	PHASE4	COMPLETED	Study of the Effects of Current Drug Treatments on Levels of Certain Brain Chemicals in Alzheimer’s Disease
NCT00120874	PHASE4	COMPLETED	Memantine and Comprehensive, Individualized Management of Alzheimer’s Disease and Caregiver Training
NCT00142324	PHASE4	UNKNOWN	CALM-AD
NCT00165724	PHASE4	COMPLETED	Alzheimer’s Disease Long-term Follow-up Study (ALF Study)
NCT00165750	PHASE4	TERMINATED	Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients
NCT00202124	PHASE4	COMPLETED	Double Blind Study of Trp01 in Patients With Alzheimer’s Disease
NCT00208819	PHASE4	COMPLETED	A Comparison of Two Standard Therapies in the Management of Dementia With Agitation
NCT00216515	PHASE4	COMPLETED	The Efficacy of Galantamine on the Attention and the Frontal Function of the Patients With Dementia of Alzheimer Type
NCT00230568	PHASE4	COMPLETED	EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer’s Disease (AD)
NCT00234637	PHASE4	COMPLETED	Rivastigmine Monotherapy and Combination Therapy With Memantine in Patients With Moderately Severe Alzheimer’s Disease Who Failed to Benefit From Previous Cholinesterase Inhibitor Treatment
NCT00245206	PHASE4	COMPLETED	Side Effects of Newer Antipsychotics in Older Adults
NCT00254033	PHASE4	COMPLETED	Apathy Associated With Alzheimer’s Disease
NCT00260624	PHASE4	COMPLETED	Escitalopram Treatment of Patients With Agitated Dementia
NCT00303277	PHASE4	COMPLETED	Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
NCT00305903	PHASE4	COMPLETED	Safety and Tolerability of Rivastigmine With Add-on Memantine in Patients With Probable Alzheimer’s Disease
NCT00306124	PHASE4	UNKNOWN	Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dementia/Mild Cognitive Impairment
NCT00334906	PHASE4	COMPLETED	Study of Memantine in Assessment of Selected Measures of Volumetric Magnetic Resonance Imaging (MRI) and Cognition in Moderate AD (Alzheimer’s Disease)
NCT00369603	PHASE4	TERMINATED	Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer’s Disease Patients
NCT00375557	PHASE4	WITHDRAWN	Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients
NCT00381381	PHASE4	COMPLETED	The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer’s Disease
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00401167	PHASE4	COMPLETED	Memantine for Agitation and Aggression in Severe Alzheimer’s Disease
NCT00403520	PHASE4	COMPLETED	Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers
NCT00417482	PHASE4	COMPLETED	Antipsychotic Discontinuation in Alzheimer’s Disease
NCT00443014	PHASE4	COMPLETED	The Dementia Study in Northern Norway
NCT00469456	PHASE4	COMPLETED	Effect of Memantine on Functional Communication in Patients With Alzheimer’s Disease
NCT00476008	PHASE4	COMPLETED	Delaying the Progression of Driving Impairment in Individuals With Mild Alzheimer’s Disease
NCT00477659	PHASE4	COMPLETED	Neural Correlates In Mild Alzheimer’s Disease
NCT00480870	PHASE4	COMPLETED	The Effect of Anticholinesterase Drugs on Sleep in Alzheimer’s Disease Patients
NCT00495820	PHASE4	COMPLETED	Methylphenidate for Apathy in Alzheimer’s Dementia: A Controlled Study
NCT00523666	PHASE4	UNKNOWN	Diffusion Tensor Weighted MRI in Alzheimer’s Disease Modifying Treatment Effects of Galantamine (Reminyl®)
NCT00549601	PHASE4	COMPLETED	Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer’s Disease
NCT00551161	PHASE4	COMPLETED	Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer’s Disease
NCT00561392	PHASE4	COMPLETED	Clinical Effectiveness of 10 cm^2 Rivastigmine Patch in Patients With Alzheimer’s Disease