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GABRP

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Summary

GABRP (gamma-aminobutyric acid type A receptor subunit pi, HGNC:4089) is a protein-coding gene on chromosome 5q35.1, encoding Gamma-aminobutyric acid receptor subunit pi (O00591). Pi subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA).

The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. The subunit encoded by this gene is expressed in several non-neuronal tissues including the uterus and ovaries. This subunit can assemble with known GABA A receptor subunits, and the presence of this subunit alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2568 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 67 total
  • Druggable target: yes — 15 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_014211

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:4089
Approved symbolGABRP
Namegamma-aminobutyric acid type A receptor subunit pi
Location5q35.1
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000094755
Ensembl biotypeprotein_coding
OMIM602729
Entrez2568

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000265294, ENST00000518122, ENST00000518525, ENST00000519137, ENST00000519196, ENST00000519385, ENST00000519598, ENST00000521009, ENST00000521481, ENST00000522868, ENST00000862231

RefSeq mRNA: 2 — MANE Select: NM_014211 NM_001291985, NM_014211

CCDS: CCDS4375, CCDS75368

Canonical transcript exons

ENST00000265294 — 10 exons

ExonStartEnd
ENSE00002127168170783725170783874
ENSE00003888765170805716170805853
ENSE00003889817170797466170797548
ENSE00003889879170811956170814047
ENSE00003891512170789129170789247
ENSE00003892133170794231170794298
ENSE00003893713170808600170808752
ENSE00003895416170788574170788668
ENSE00003895461170809568170809755
ENSE00003896002170795208170795425

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 98.97.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0355 / max 2243.9919, expressed in 295 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
601623.9276238
601610.107965

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
nasal cavity epitheliumUBERON:000538498.97gold quality
epithelium of nasopharynxUBERON:000195198.32gold quality
nasopharynxUBERON:000172898.30gold quality
palpebral conjunctivaUBERON:000181297.63gold quality
lower esophagus mucosaUBERON:003583497.61gold quality
olfactory segment of nasal mucosaUBERON:000538696.49gold quality
endometriumUBERON:000129595.04gold quality
nasal cavity mucosaUBERON:000182694.86gold quality
epithelium of mammary glandUBERON:000324494.78gold quality
mammary ductUBERON:000176594.45gold quality
mucosa of paranasal sinusUBERON:000503094.09gold quality
esophagus squamous epitheliumUBERON:000692093.67gold quality
amniotic fluidUBERON:000017393.56gold quality
epithelium of bronchusUBERON:000203192.07gold quality
bronchusUBERON:000218591.43gold quality
pharyngeal mucosaUBERON:000035591.32gold quality
bronchial epithelial cellCL:000232891.14gold quality
epithelium of esophagusUBERON:000197690.52gold quality
mammary glandUBERON:000191190.04gold quality
thoracic mammary glandUBERON:000520089.96gold quality
pancreatic ductal cellCL:000207989.61gold quality
upper leg skinUBERON:000426288.27gold quality
minor salivary glandUBERON:000183087.92gold quality
esophagus mucosaUBERON:000246987.21gold quality
oral cavityUBERON:000016785.03gold quality
skin of legUBERON:000151184.68gold quality
skin of abdomenUBERON:000141682.99gold quality
vaginaUBERON:000099682.63gold quality
mouth mucosaUBERON:000372981.92gold quality
zone of skinUBERON:000001481.80gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 10.

ExperimentMarker?Max mean expression
E-GEOD-75688yes1885.88
E-MTAB-6701yes1497.58
E-CURD-7yes833.32
E-ENAD-21yes728.84
E-MTAB-8495yes492.67
E-CURD-114yes60.18
E-MTAB-10287yes50.83
E-HCAD-1yes12.27
E-MTAB-9388yes8.60
E-MTAB-6819no287.66
E-MTAB-7008no211.75
E-MTAB-9801no3.80
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting GABRP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-29A-3P100.0073.111835
HSA-MIR-29B-3P100.0073.181833
HSA-MIR-29C-3P100.0073.151833
HSA-MIR-4533100.0069.482758
HSA-MIR-5692A100.0074.406850
HSA-MIR-3163100.0077.238605
HSA-MIR-366299.9973.825684
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-4482-3P99.9872.503147
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-548J-3P99.9472.614881
HSA-MIR-552-5P99.9368.561583
HSA-MIR-548AE-3P99.9372.664867
HSA-MIR-548AH-3P99.9372.544872
HSA-MIR-548AM-3P99.9372.544872
HSA-MIR-548AQ-3P99.9372.664867
HSA-MIR-6508-5P99.9270.672465
HSA-MIR-497-5P99.9271.832674
HSA-MIR-205-3P99.9269.923165
HSA-MIR-589-3P99.9169.622088
HSA-MIR-15A-5P99.9072.802787
HSA-MIR-15B-5P99.9072.782798
HSA-MIR-16-5P99.9072.802780
HSA-MIR-195-5P99.9072.812805
HSA-MIR-808799.9069.551351
HSA-MIR-6783-3P99.8967.922059

Literature-anchored findings (GeneRIF, showing 11)

  • Data suggest that GABRP is progressively down-regulated with tumour-progression, and that it may be useful as a prognostic marker in breast cancer. (PMID:16187283)
  • HOXA10 expression leads to production of a less progestin-responsive GABA receptor subtype pi (PMID:20103740)
  • data reveal a GABRP-ERK1/2-cytokeratin axis that maintains the migratory phenotype of basal-like breast cancer (PMID:25012653)
  • genetic polymorphism is associated with systemic lupus erythematosus in female patients (PMID:26634217)
  • Hypomethylation of the GABRP promoter is associated with aggressive phenotype of ovarian cancer. (PMID:28524180)
  • rs505474, rs1398175, and rs4868029 in the GABRA2, GABRA4, and GABRP genes, respectively, allele frequencies were significantly different between patients and controls.Four haplotypes were significantly associated with Bipolar Disorder (TA and AG for rs3815762 and rs4868029 in GABRP, GG for rs11636988 and rs8024256 in GABRB3 and GAGG for rs2197414, rs4921195, rs13188991, and rs11956731 in GABRA6. (PMID:29135068)
  • Use of a human embryonic stem cell model to discover GABRP, WFDC2, VTCN1 and ACTC1 as markers of early first trimester human trophoblast. (PMID:32359161)
  • GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling. (PMID:34023418)
  • The Emerging Roles of pi Subunit-Containing GABAA Receptors in Different Cancers. (PMID:34790061)
  • GABRP promotes CD44s-mediated gemcitabine resistance in pancreatic cancer. (PMID:35846884)
  • GABRP Promotes the Metastasis of Pancreatic Cancer by Activation of the MEK/ERK Signaling Pathway. (PMID:37326897)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusGabrpENSMUSG00000020159
rattus_norvegicusGabrpENSRNOG00000032417

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Gamma-aminobutyric acid receptor subunit pi — O00591 (reviewed: O00591)

Alternative names: GABA(A) receptor subunit pi

All UniProt accessions (8): O00591, E5RG98, E5RGF7, E5RHF6, E5RHU0, E5RI57, E5RK74, E7EWG0

UniProt curated annotations — full annotation on UniProt →

Function. Pi subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interfaces. When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Pi-containing GABAARs are mostly located in peripheral tissues. In the uterus, pi subunits modulate uterus contraction by altering the sensitivity of GABAARs to pregnanolone. In the lungs, pi-containing GABAARs contribute to pulmonary fluid transport via luminal secretion of chloride.

Subunit / interactions. Heteropentamer, formed by a combination of alpha (GABRA1-6), beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho (GABRR1-3), pi (GABRP) and theta (GABRQ) chains, each subunit exhibiting distinct physiological and pharmacological properties.

Subcellular location. Cell membrane. Apical cell membrane.

Tissue specificity. Most abundant in non-neuronal tissues including the uterus, ovaries and also expressed in lung, thymus and prostate. Expressed in the hippocampus.

Activity regulation. Allosterically potentiated by alphaxalone. Allosterically inhibited by pregnenolone sulfate. Inhibited by lanthanum. High sensitivity to inhibition by zinc. The binding of pi subunit with other GABAAR subunits alters the receptor sensitivity to modulatory agents such as pregnanolone.

Domain organisation. GABAARs subunits share a common topological structure: a peptide sequence made up of a long extracellular N-terminal, four transmembrane domains, intracellular or cytoplasmic domain located between the third and the fourth transmembrane domains.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRP sub-subfamily.

RefSeq proteins (2): NP_001278914, NP_055026* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR006028GABAA/Glycine_rcptFamily
IPR006029Neurotrans-gated_channel_TMDomain
IPR006201Neur_channelFamily
IPR006202Neur_chan_lig-bdDomain
IPR008100GABAAp_rcptFamily
IPR018000Neurotransmitter_ion_chnl_CSConserved_site
IPR036719Neuro-gated_channel_TM_sfHomologous_superfamily
IPR036734Neur_chan_lig-bd_sfHomologous_superfamily
IPR038050Neuro_actylchol_recHomologous_superfamily
IPR047032GABAAR_pi_TMDomain

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 1 shown:

  • chloride(in) = chloride(out) (RHEA:29823)

UniProt features (47 total): strand 14, helix 11, glycosylation site 5, turn 4, topological domain 4, transmembrane region 4, sequence variant 2, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

2 structures.

PDBMethodResolution (Å)
8VSZELECTRON MICROSCOPY3.07
8VV0ELECTRON MICROSCOPY3.1

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O00591-F179.360.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 160–174

Glycosylation sites (5): 43, 102, 145, 196, 228

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 159 (showing top): MODULE_64, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, SMID_BREAST_CANCER_ERBB2_DN, MARTINEZ_RB1_TARGETS_UP, GOBP_CHLORIDE_TRANSPORT, YANG_BREAST_CANCER_ESR1_DN, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SYNAPTIC_SIGNALING, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, RICKMAN_HEAD_AND_NECK_CANCER_A, GOCC_APICAL_PLASMA_MEMBRANE, TGGNNNNNNKCCAR_UNKNOWN, MODULE_6

GO Biological Process (5): synaptic transmission, GABAergic (GO:0051932), chloride transmembrane transport (GO:1902476), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (6): GABA-A receptor activity (GO:0004890), GABA-gated chloride ion channel activity (GO:0022851), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), chloride channel activity (GO:0005254)

GO Cellular Component (6): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), chloride channel complex (GO:0034707), synapse (GO:0045202), GABA-A receptor complex (GO:1902711), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
chemical synaptic transmission1
chloride transport1
monoatomic anion transmembrane transport1
transport1
monoatomic anion transport1
inorganic anion transport1
monoatomic ion transport1
transmembrane transport1
GABA receptor activity1
chloride channel activity1
transmitter-gated monoatomic ion channel activity1
ligand-gated monoatomic anion channel activity1
signaling receptor activity1
monoatomic ion transmembrane transporter activity1
channel activity1
ligand-gated monoatomic ion channel activity1
monoatomic anion channel activity1
chloride transmembrane transporter activity1
membrane1
cell periphery1
apical part of cell1
plasma membrane region1
monoatomic ion channel complex1
cell junction1
GABA receptor complex1
cellular anatomical structure1

Protein interactions and networks

STRING

838 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
GABRPCLINT1Q14677639
GABRPKCNN4O15554577
GABRPSLC6A3Q01959569
GABRPAGR3Q8TD06423
GABRPRNF222A6NCQ9414
GABRPNR3C1P04150412
GABRPGABBR2O75899406
GABRPERP27Q96DN0375
GABRPGAD1Q99259373
GABRPVGLL1Q99990348
GABRPANKRD66B4E2M5346
GABRPVTCN1Q7Z7D3345
GABRPISYNA1Q9NPH2338
GABRPGABBR1Q9UBS5323
GABRPKRT17Q04695320

IntAct

0 interactions, top by confidence:

BioGRID (2): GABRP (Affinity Capture-RNA), HIST1H1E (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A8XF54, A8XNX8, G5ECJ0, G5ECT0, G5EDN0, G5EG88, O00591, O09028, O16926, O18276, O35119, O70174, O76554, P09478, P09482, P09483, P17644, P18845, P20781, P25162, P41849, P45963, P48167, P48168, P48181, P48182, P48994, P54245, P54246, Q09453, Q18812, Q19351, Q21005, Q21974, Q23022, Q27218, Q5EA06, Q5IS77, Q60S81, Q86LG1

Diamond homologs: A8MPY1, D1LYT2, F1R8P4, G5EBR3, O00591, O09028, O14764, O18276, O75311, O93430, P07727, P08219, P08220, P0C2W5, P10063, P10064, P14867, P15431, P16305, P18505, P18506, P18507, P18508, P19019, P19150, P19969, P20236, P20237, P20781, P21548, P22300, P22723, P22771, P22933, P23415, P23416, P23574, P23576, P24045, P24046

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance57
Likely benign5
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1481 predictions. Top by Δscore:

VariantEffectΔscore
5:170794229:A:AGacceptor_gain1.0000
5:170794230:G:GGacceptor_gain1.0000
5:170794230:GGA:Gacceptor_gain1.0000
5:170794297:TGGTA:Tdonor_loss1.0000
5:170794299:G:GCdonor_loss1.0000
5:170794300:TAAG:Tdonor_loss1.0000
5:170795203:CCCA:Cacceptor_loss1.0000
5:170795204:CCAG:Cacceptor_loss1.0000
5:170795206:AG:Aacceptor_gain1.0000
5:170795206:AGG:Aacceptor_loss1.0000
5:170795207:GG:Gacceptor_gain1.0000
5:170795423:CAGG:Cdonor_loss1.0000
5:170795424:AGGTA:Adonor_loss1.0000
5:170795425:GGTA:Gdonor_loss1.0000
5:170795426:GTACG:Gdonor_loss1.0000
5:170795427:T:Adonor_loss1.0000
5:170797464:A:AGacceptor_gain1.0000
5:170797465:G:GGacceptor_gain1.0000
5:170797465:GA:Gacceptor_gain1.0000
5:170797544:AAGCT:Adonor_gain1.0000
5:170797545:AGCT:Adonor_gain1.0000
5:170797545:AGCTG:Adonor_loss1.0000
5:170797546:GCT:Gdonor_gain1.0000
5:170797546:GCTG:Gdonor_gain1.0000
5:170797547:CT:Cdonor_gain1.0000
5:170797547:CTGTA:Cdonor_loss1.0000
5:170797549:G:Cdonor_loss1.0000
5:170797549:G:GGdonor_gain1.0000
5:170797550:T:TCdonor_loss1.0000
5:170797551:AA:Adonor_loss1.0000

AlphaMissense

2917 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:170795241:T:AW92R1.000
5:170795241:T:CW92R1.000
5:170795243:G:CW92C1.000
5:170795243:G:TW92C1.000
5:170795313:T:AW116R1.000
5:170795313:T:CW116R1.000
5:170795315:G:CW116C1.000
5:170795315:G:TW116C1.000
5:170789233:G:CR53T0.999
5:170789233:G:TR53M0.999
5:170789236:C:AP54H0.999
5:170795217:G:CA84P0.999
5:170795224:T:AI86K0.999
5:170795230:T:CL88P0.999
5:170795236:A:CQ90P0.999
5:170795239:G:CR91P0.999
5:170795242:G:CW92S0.999
5:170795320:C:AP118Q0.999
5:170795320:C:GP118R0.999
5:170795383:T:CL139P0.999
5:170795389:G:CR141P0.999
5:170795404:G:AG146D0.999
5:170795404:G:TG146V0.999
5:170795410:T:AV148D0.999
5:170795413:T:CL149P0.999
5:170797486:G:AC160Y0.999
5:170797527:T:AC174S0.999
5:170797528:G:AC174Y0.999
5:170797528:G:CC174S0.999
5:170797545:A:CS180R0.999

dbSNP variants (sampled 300 via entrez): RS1000015141 (5:170802672 A>T), RS1000195492 (5:170806402 A>G), RS1000240872 (5:170812636 T>A), RS1000360728 (5:170796078 G>T), RS1000369578 (5:170785613 C>A,T), RS1000383511 (5:170800151 C>T), RS1000405494 (5:170785614 C>A), RS1000768261 (5:170789381 T>C), RS1000870600 (5:170790785 C>A,G,T), RS1000907350 (5:170786705 G>A), RS1000965878 (5:170786903 G>A), RS1000974963 (5:170784176 T>C,G), RS1001016620 (5:170810826 C>T), RS1001060961 (5:170794627 A>G), RS1001231784 (5:170786321 G>T)

Disease associations

OMIM: gene MIM:602729 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

StudyTraitp-value
GCST012118_2Response to immune checkpoint inhibitors in melanoma (immune-related adverse events)6.000000e-06
GCST012490_548Femur bone mineral density x serum urate levels interaction6.000000e-09

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0011053immune system toxicity
EFO:0600023response to immune checkpoint inhibitor
EFO:0004531urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2093872 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 442,649 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1082407ENZALUTAMIDE49,652
CHEMBL12DIAZEPAM492,281
CHEMBL1544LIOTHYRONINE423,700
CHEMBL1568698GANAXOLONE41,657
CHEMBL207538BREXANOLONE41,585
CHEMBL3183409APALUTAMIDE44,076
CHEMBL407FLUMAZENIL47,150
CHEMBL452CLONAZEPAM433,297
CHEMBL268254DELORAZEPAM21,308
CHEMBL275638FLAVONE288,985
CHEMBL287631PROGABIDE23,853
CHEMBL454095ABECARNIL2566
CHEMBL8260BAICALEIN28,592
CHEMBL273481MUSCIMOL15,759
CHEMBL96GAMMA-AMINOBUTYRIC ACID1160,188

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

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs10036156Efficacy3antidepressants;Selective serotonin reuptake inhibitors;venlafaxineMajor Depressive Disorder

PharmGKB variants

2 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs10036156GABRP30.001antidepressants;Selective serotonin reuptake inhibitors;venlafaxine
rs73800947GABRP0.000

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — GABAA receptors

ChEMBL bioactivities

474 potent at pChembl≥5 of 511 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.00IC500.1nMCHEMBL454349
9.80IC500.16nMCHEMBL309517
9.70IC500.2nMCHEMBL4747460
9.62IC500.24nMCHEMBL79037
9.40IC500.3981nMCGS-8216
9.40IC500.4nMCHEMBL1271047
9.34IC500.46nMCHEMBL78730
9.31IC500.49nMCHEMBL76263
9.30IC500.5nMCHEMBL5266498
9.30IC500.5nMCHEMBL5290464
9.30IC500.5nMCHEMBL5280240
9.30IC500.5nMCHEMBL49141
9.30IC500.5nMCHEMBL1518572
9.22IC500.6026nMCGS-9896
9.22IC500.6nMCHEMBL419096
9.12IC500.76nMCHEMBL540583
9.10IC500.79nMCHEMBL77226
9.10IC500.8nMCHEMBL5265845
9.10IC500.8nMCHEMBL5291368
9.10IC500.8nMCHEMBL5271392
9.07Ki0.85nMCLONAZEPAM
9.05Ki0.9nMFLUMAZENIL
9.05IC500.9nMCHEMBL5285377
9.00Ki1nMCHEMBL3410222
9.00IC501nMBETA-CCM
9.00IC501nMCHEMBL454606
9.00IC501nMCHEMBL1337028
9.00IC501nMCHEMBL509197
9.00IC501nMABECARNIL
9.00Ki1nMCHEMBL54341
9.00Ki1nMCHEMBL348367
8.96IC501.1nMCHEMBL444586
8.77Ki1.7nMCHEMBL154342
8.74IC501.8nMCHEMBL444050
8.70IC502nMMUSCIMOL
8.66IC502.2nMCHEMBL80610
8.64IC502.3nMFIPRONIL
8.55IC502.8nMCHEMBL75642
8.55Ki2.8nMCHEMBL372281
8.55IC502.8nMDELORAZEPAM
8.52Ki3nMCHEMBL265547
8.52IC503nMCHEMBL510764
8.52IC503nMCHEMBL5266558
8.52IC503nMCHEMBL2262044
8.52IC503nMCHEMBL499814
8.52IC503nMCHEMBL1161036
8.48IC503.3nMCHEMBL75642
8.40IC503.981nMCHEMBL301605
8.40Ki4nMCHEMBL330116
8.40Ki4nMCHEMBL3407528

PubChem BioAssay actives

409 with measured affinity, of 875 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
2-(4-methoxyphenyl)-1H-pyrazolo[4,3-c]quinolin-3-one40988: Inhibition on Benzodiazepine receptoric500.0001uM
ethyl 4-(methoxymethyl)-5-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0002uM
ethyl 4-methyl-5-propan-2-yloxy-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0004uM
2-phenyl-3aH-pyrazolo[4,3-c]quinolin-3-one40988: Inhibition on Benzodiazepine receptoric500.0004uM
ethyl 4-(methoxymethyl)-6-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0005uM
ethyl 4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0005uM
ethyl 6-methoxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0005uM
ethyl 4-(methoxymethyl)-6-propoxy-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0005uM
ethyl 6-hydroxy-4-(methoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0005uM
2-(4-chlorophenyl)-3aH-pyrazolo[4,3-c]quinolin-3-one40988: Inhibition on Benzodiazepine receptoric500.0006uM
5-[[3-(1,3-benzodioxol-5-yl)-6-iminopyridazin-1-yl]methyl]-1,2-thiazol-3-one;hydrobromide72153: Affinity for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]gabazine antagonist from rat brain preparations.ic500.0008uM
propan-2-yl 16-(methoxymethyl)-3,6,11,14-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2,4,6,8,12,14,16-octaene-15-carboxylate1932305: Inhibition of GABAA receptor (unknown origin)ic500.0008uM
propan-2-yl 4-(methoxymethyl)-6,9,14,21-tetrazapentacyclo[11.8.0.02,10.03,8.015,20]henicosa-1(21),2,4,6,8,10,12,15(20)-octaene-5-carboxylate1932305: Inhibition of GABAA receptor (unknown origin)ic500.0008uM
propan-2-yl 15-(methoxymethyl)-4-propan-2-yl-5-oxa-10,13-diazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2(6),3,7,11,13,15-heptaene-14-carboxylate1932305: Inhibition of GABAA receptor (unknown origin)ic500.0008uM
Clonazepam239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membraneski0.0008uM
15-(methoxymethyl)-14-(5-methyl-1,2-oxazol-3-yl)-4-propan-2-yl-5-oxa-3,10,13-triazatetracyclo[7.7.0.02,6.011,16]hexadeca-1(9),2(6),3,7,11,13,15-heptaene1932305: Inhibition of GABAA receptor (unknown origin)ic500.0009uM
Flumazenil239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membraneski0.0009uM
ethyl 9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0010uM
methyl 9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0010uM
propyl 9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0010uM
tert-butyl 9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0010uM
7-chloro-5-methyl-3-(2-phenylethynyl)-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one1196597: Displacement of [3H]flumazenil from rat cortex GABAA receptor BDZ binding site expressed in HEK293 cells by competition binding assayki0.0010uM
6-bromo-2-(3-nitrophenyl)chromen-4-one72729: Binding affinity towards benzodiazepine site in GABAA receptorki0.0010uM
(2-methoxyphenyl)methyl 8-chloro-5-oxido-3,3a-dihydropyrazolo[5,1-c][1,2,4]benzotriazin-5-ium-3-carboxylate41860: Binding affinity towards Benzodiazepine receptor from bovine brain membrane using [3H]Ro-151788 as radioligandki0.0010uM
propan-2-yl 4-(methoxymethyl)-6-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0010uM
(2-methoxyphenyl)methyl 8-chloropyrazolo[5,1-c][1,2,4]benzotriazine-3-carboxylate41860: Binding affinity towards Benzodiazepine receptor from bovine brain membrane using [3H]Ro-151788 as radioligandki0.0017uM
5-(aminomethyl)-1,2-oxazol-3-one72155: Binding affinity in vivo for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]-GABA agonist from rat brain preparations after iv injection.ic500.0020uM
Fipronil242615: In vitro insecticidal activity as inhibition of [3H]EBOB binding to Gamma-aminobutyric acid GABA-A receptor of housefly neuronal membranesic500.0023uM
9-chloro-2-phenyl-6H-triazolo[1,2-a][1,2,4]benzotriazine-1,5-dione239299: Displacement of [3H]flumazenil from bovine benzodiazepine receptor GABA-A channel of brain membraneski0.0028uM
7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one40974: In vitro displacement of [3H]-diazepam from GABA-A Benzodiazepine receptoric500.0028uM
3-isothiocyanato-9H-pyrido[3,4-b]indole1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0030uM
9H-pyrido[3,4-b]indole-3-carbonitrile1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0030uM
3-(6,7-difluoro-1,3-benzoxazol-2-yl)-1,3a,4,5,6,7,8,8a-octahydrocyclohepta[d]imidazol-2-one40986: Binding affinity against GABA-A benzodiazepine receptorki0.0030uM
(5aR,7R,9aS,11aS)-2-amino-7-hydroxy-9a,11a-dimethyl-3,3a,3b,4,5,5a,6,7,8,9,9b,11-dodecahydronaphtho[2,1-e]indol-10-one72153: Affinity for gamma-aminobutyric-acid A receptor measured by its ability to displace [3H]gabazine antagonist from rat brain preparations.ic500.0030uM
3-propoxy-9H-pyrido[3,4-b]indole1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0030uM
1-(9H-pyrido[3,4-b]indol-3-yl)butan-1-one1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0030uM
8-fluoro-5-methyl-3-(2-phenylethynyl)-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one1196597: Displacement of [3H]flumazenil from rat cortex GABAA receptor BDZ binding site expressed in HEK293 cells by competition binding assayki0.0040uM
methyl 6-hydroxy-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0040uM
2-phenyl-6H-[1,2,4]triazolo[1,5-c]quinazolin-5-one40986: Binding affinity against GABA-A benzodiazepine receptorki0.0040uM
17-chloro-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene1932305: Inhibition of GABAA receptor (unknown origin)ic500.0040uM
5-nitro-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene1932305: Inhibition of GABAA receptor (unknown origin)ic500.0040uM
5-bromo-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene1932305: Inhibition of GABAA receptor (unknown origin)ic500.0040uM
17-methoxy-9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene1932305: Inhibition of GABAA receptor (unknown origin)ic500.0040uM
9,12,20-triazapentacyclo[11.7.0.02,10.03,8.014,19]icosa-1(13),2(10),3,5,7,11,14,16,18-nonaene1932305: Inhibition of GABAA receptor (unknown origin)ic500.0040uM
methyl 6-(benzylamino)-9H-pyrido[3,4-b]indole-3-carboxylate1932290: Displacement of [3H]flunitrazepam from GABAA (unknown origin ) receptor by radioligand binding assayic500.0040uM
Diazepam1934094: Inhibition of GABA-A receptor (unknown origin)ic500.0042uM
4-acetyl-13-(4-chlorophenyl)-5-thia-13,14-diazatricyclo[8.4.0.02,6]tetradeca-1(10),2(6),3-trien-12-one40977: Binding affinity for GABA-A Benzodiazepine receptorki0.0042uM
1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(trifluoromethylsulfinyl)pyrazole242615: In vitro insecticidal activity as inhibition of [3H]EBOB binding to Gamma-aminobutyric acid GABA-A receptor of housefly neuronal membranesic500.0042uM
2-amino-N-[4-chloro-2-(2-chlorobenzoyl)phenyl]acetamide40974: In vitro displacement of [3H]-diazepam from GABA-A Benzodiazepine receptoric500.0048uM
3-(7-fluoro-1,3-benzoxazol-2-yl)-1,3a,4,5,6,7,8,8a-octahydrocyclohepta[d]imidazol-2-one40986: Binding affinity against GABA-A benzodiazepine receptorki0.0050uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects cotreatment, increases expression, decreases methylation5
sodium arseniteincreases abundance, increases expression, affects expression, decreases expression, affects cotreatment4
bisphenol Aaffects expression, decreases expression, increases activity3
Estradiolaffects expression, affects cotreatment, decreases expression, increases activity3
Tretinoindecreases expression, increases expression3
mercuric bromideincreases expression, affects cotreatment2
Ethinyl Estradiolaffects expression, decreases expression2
Nickeldecreases expression2
Progesteroneaffects cotreatment, decreases expression, affects localization, affects reaction, increases expression2
Tobacco Smoke Pollutionaffects expression, decreases expression2
trichostatin Aincreases expression1
cordycepindecreases expression1
tebuconazoledecreases expression1
CGP 52608affects binding, increases reaction1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
dorsomorphinaffects cotreatment, increases expression1
(+)-JQ1 compounddecreases expression1
Resveratrolaffects cotreatment, decreases expression1
Zoledronic Aciddecreases expression1
Panobinostataffects cotreatment, increases expression1
Air Pollutantsdecreases expression, increases abundance1
Arsenicaffects cotreatment, increases abundance, increases expression1
Benzo(a)pyreneaffects methylation, decreases methylation1
Cadmiumdecreases expression, increases abundance1
Calcitriolincreases expression1
Copperaffects cotreatment, decreases expression1
Cytarabineincreases expression1
DDTdecreases expression, increases activity1
Demecolcineincreases expression1
Diethylhexyl Phthalateincreases expression1

ChEMBL screening assays

185 unique, capped per target: 166 binding, 15 functional, 3 toxicity, 1 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3363914BindingDisplacement of [3H]Muscimol from rat GABAA receptor at 10 uM after 90 mins by microbeta counting analysisGriseorhodins D-F, neuroactive intermediates and end products of post-PKS tailoring modification in Griseorhodin biosynthesis. — J Nat Prod
CHEMBL4810229ADMETInhibition of GABA A receptor (unknown origin) at 0.1 to 1 uMDiscovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — J Med Chem
CHEMBL5335653ToxicityAntagonist activity at GABA-A (unknown origin)Discovery of a Novel Bifunctional Steroid Analog, YXG-158, as an Androgen Receptor Degrader and CYP17A1 Inhibitor for the Treatment of Enzalutamide-Resistant Prostate Cancer. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_YA49IDG-HEK293T-GABRP-V5-OETransformed cell lineFemale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 79

This page pulls from 79 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot