Details for: ADGRG4

Gene ID: 139378

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ADGRG4

Ensembl ID: ENSG00000156920

Description: adhesion G protein-coupled receptor G4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • BEST4+ enteroycte CL4030026
    CSI 11.55
    rCSI 14.37%
    PRS 99.77
  • enteroendocrine cell of small intestine CL0009006
    CSI 8.18
    rCSI 18.02%
    PRS 99.97
  • retina horizontal cell CL0000745
    CSI 6.72
    rCSI 10.24%
    PRS 99.9
  • enteroendocrine cell CL0000164
    CSI 6.24
    rCSI 8.53%
    PRS 99.82
  • M cell of gut CL0000682
    CSI 5.51
    rCSI 5.85%
    PRS 99.88
  • type EC enteroendocrine cell CL0000577
    CSI 4
    rCSI 14.21%
    PRS 99.97
  • type L enteroendocrine cell CL0002279
    CSI 3.75
    rCSI 7.04%
    PRS 99.97

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Adhesion G protein-coupled receptor G4 ([ADGRG4](/details-gene/139378)), also known as GPR112, is a protein-coding gene located on the X chromosome ([Link](https://doi.org/10.1038/nature03440)). It belongs to the adhesion G protein-coupled receptor (GPCR) family, characterized by a large N-terminal extracellular domain involved in cell-cell and cell-matrix interactions ([Link](https://doi.org/10.1016/s0014-5793(02)03574-3)). Functionally, it is involved in [G protein-coupled receptor signaling](/details-go/GO:0007186) pathways, particularly those activating adenylate cyclase ([Link](https://www.ebi.ac.uk/QuickGO/term/GO:0007189)). **Overall**, expression data reveals that [ADGRG4](/details-gene/139378) is a highly specific marker for specialized epithelial cells in the intestine, with its most significant expression observed in [BEST4+ enteroycytes](/details-cell/CL4030026), various types of [enteroendocrine cells](/details-cell/CL0000164), and [M cells of the gut](/details-cell/CL0000682). Its notable expression in [retina horizontal cells](/details-cell/CL0000745) suggests a role in neuronal signaling as well. A clinical association has been noted in OMIM ([153245](https://omim.org/entry/301085)). ## Cellular Roles and Expression Landscape The expression profile of [ADGRG4](/details-gene/139378) points to a specialized function within distinct cellular niches, primarily in the gastrointestinal tract and the retina. **Overall**, the gene's significance is highest in intestinal epithelial cells responsible for nutrient sensing, hormone secretion, and mucosal immunity. It is a top marker for [BEST4+ enteroycytes](/details-cell/CL4030026) (CSI: 11.55), a recently described cell type with roles in ion transport. It is also highly significant in several [enteroendocrine cell](/details-cell/CL0000164) populations, including those of the [small intestine](/details-cell/CL0009006) (CSI: 8.18), [type EC enteroendocrine cells](/details-cell/CL0000577) (CSI: 4.00), and [type L enteroendocrine cells](/details-cell/CL0002279) (CSI: 3.75). This is consistent with literature identifying it as a marker for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas ([Link](https://doi.org/10.1038/modpathol.2008.174)). Furthermore, its high significance in [M cells of the gut](/details-cell/CL0000682) (CSI: 5.51) suggests a potential role in mucosal antigen sampling. Outside the gut, [ADGRG4](/details-gene/139378) is a significant marker for [retina horizontal cells](/details-cell/CL0000745) (CSI: 6.72), indicating a function in synaptic modulation and lateral inhibition within the neural circuitry of the retina. The common thread among these diverse cell types is a role in environmental sensing and intercellular communication, whether in the context of the gut lumen or the retinal neural network. ## Pathways and Molecular Function Consistent with its classification, the molecular function of [ADGRG4](/details-gene/139378) is centered on its activity as a [G protein-coupled receptor](/details-go/GO:0004930) located in the [plasma membrane](/details-go/GO:0005886). It participates in the [G protein-coupled receptor signaling pathway](/details-go/GO:0007186) and more specifically the [adenylate cyclase-activating G protein-coupled receptor signaling pathway](/details-go/GO:0007189). This suggests that ligand binding to the extracellular domain of [ADGRG4](/details-gene/139378) initiates an intracellular signaling cascade mediated by G proteins and cyclic AMP. This mechanism is fundamental for translating extracellular signals—potentially from cell-cell adhesion or soluble factors—into a cellular response, which aligns with its high expression in secretory and sensory cell types like [enteroendocrine cells](/details-cell/CL0000164). This dual role in adhesion and signaling is a defining feature of the adhesion GPCR family ([Link](https://doi.org/10.1124/pr.114.009647)). ## Research Directions The highly specific expression pattern of [ADGRG4](/details-gene/139378) in sensory and secretory cell types of the gut and retina opens up several avenues for investigation. **Proposed Hypotheses:** 1. Given its high expression in diverse [enteroendocrine cells](/details-cell/CL0000164), [ADGRG4](/details-gene/139378) may function as a receptor for luminal components (e.g., microbial metabolites or dietary nutrients), coupling gut environmental sensing to the regulation of metabolic hormone secretion (e.g., serotonin, GLP-1). 2. In [retina horizontal cells](/details-cell/CL0000745), [ADGRG4](/details-gene/139378) may mediate cell-cell adhesion and communication within the outer plexiform layer, potentially modulating synaptic strength and contributing to the processing of visual signals. **Experimental Approach:** To test the first hypothesis regarding its role in enteroendocrine function, a CRISPR-Cas9 knockout of [ADGRG4](/details-gene/139378) could be generated in human intestinal organoids. These organoids, containing a mix of intestinal cell types including enteroendocrine cells, could be cultured and stimulated with a panel of candidate ligands (e.g., short-chain fatty acids, bile acids, or specific amino acids). The supernatant could then be analyzed by ELISA or mass spectrometry to quantify the secretion of key hormones like serotonin, PYY, and GLP-1. A significant difference in hormone release between wild-type and knockout organoids upon stimulation would provide direct evidence for the role of [ADGRG4](/details-gene/139378) in nutrient sensing and metabolic regulation. **Therapeutic Potential:** As a cell-surface GPCR, [ADGRG4](/details-gene/139378) is a highly druggable target. Its restricted expression pattern in specific gut epithelial cell types makes it an attractive candidate for therapies with limited off-target effects. Modulating its activity could have significant therapeutic implications: - **Activation:** Agonists targeting [ADGRG4](/details-gene/139378) on [L-cells](/details-cell/CL0002279) could be developed to increase GLP-1 secretion, representing a novel therapeutic strategy for type 2 diabetes and obesity. - **Inhibition:** Given its association with gastrointestinal neuroendocrine carcinomas ([Link](https://doi.org/10.1038/modpathol.2008.174)), antagonists or antibody-based therapies could be explored to target tumors overexpressing this receptor.

Genular Protein ID: 3148939808

Symbol: AGRG4_HUMAN

Name: G-protein coupled receptor 112

UniProtKB Accession Codes:

Q8IZF6 A2A2J1 A2A2J2 Q5EGP2 Q86SM6

Database IDs:

AGR 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 EMDB 1 Ensembl 3 GO 6 Gene3D 4 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRINTS 1 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 2 SASBDB 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12435584

Title: Novel human G protein-coupled receptors with long N-terminals containing GPS domains and Ser/Thr-rich regions.

PubMed ID: 12435584

DOI: 10.1016/s0014-5793(02)03574-3

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 12679517

Title: The G protein-coupled receptor repertoires of human and mouse.

PubMed ID: 12679517

DOI: 10.1073/pnas.0230374100

PubMed ID: 18953328

Title: Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas.

PubMed ID: 18953328

DOI: 10.1038/modpathol.2008.174

PubMed ID: 25713288

Title: International union of basic and clinical pharmacology. XCIV. Adhesion G protein-coupled receptors.

PubMed ID: 25713288

DOI: 10.1124/pr.114.009647

Sequence Information:

  • Length: 3080
  • Mass: 333368
  • Checksum: 3449BC820B251BD3
  • Sequence:
    • MKEHIIYQKL YGLILMSSFI FLSDTLSLKG KKLDFFGRGD TYVSLIDTIP ELSRFTACID 
LVFMDDNSRY WMAFSYITNN ALLGREDIDL GLAGDHQQLI LYRLGKTFSI RHHLASFQWH 
TICLIWDGVK GKLELFLNKE RILEVTDQPH NLTPHGTLFL GHFLKNESSE VKSMMRSFPG 
SLYYFQLWDH ILENEEFMKC LDGNIVSWEE DVWLVNKIIP TVDRTLRCFV PENMTIQEKS 
TTVSQQIDMT TPSQITGVKP QNTAHSSTLL SQSIPIFATD YTTISYSNTT SPPLETMTAQ 
KILKTLVDET ATFAVDVLST SSAISLPTQS ISIDNTTNSM KKTKSPSSES TKTTKMVEAM 
ATEIFQPPTP SNFLSTSRFT KNSVVSTTSA IKSQSAVTKT TSLFSTIEST SMSTTPCLKQ 
KSTNTGALPI STAGQEFIES TAAGTVPWFT VEKTSPASTH VGTASSFPPE PVLISTAAPV 
DSVFPRNQTA FPLATTDMKI AFTVHSLTLP TRLIETTPAP RTAETELTST NFQDVSLPRV 
EDAMSTSMSK ETSSKTFSFL TSFSFTGTES VQTVIDAEAT RTALTPEITL ASTVAETMLS 
STITGRVYTQ NTPTADGHLL TLMSTRSAST SKAPESGPTS TTDEAAHLFS SNETIWTSRP 
DQALLASMNT TTILTFVPNE NFTSAFHENT TYTEYLSATT NITPLKASPE GKGTTANDAT 
TARYTTAVSK LTSPWFANFS IVSGTTSITN MPEFKLTTLL LKTIPMSTKP ANELPLTPRE 
TVVPSVDIIS TLACIQPNFS TEESASETTQ TEINGAIVFG GTTTPVPKSA TTQRLNATVT 
RKEATSHYLM RKSTIAAVAE VSPFSTMLEV TDESAQRVTA SVTVSSFPDI EKLSTPLDNK 
TATTEVRESW LLTKLVKTTP RSSYNEMTEM FNFNHTYVAH WTSETSEGIS AGSPTSGSTH 
IFGEPLGAST TRISETSFST TPTDRTATSL SDGILPPQPT AAHSSATPVP VTHMFSLPVN 
GSSVVAEETE VTMSEPSTLA RAFSTSVLSD VSNLSSTTMT TALVPPLDQT ASTTIVIVPT 
HGDLIRTTSE ATVISVRKTS MAVPSLTETP FHSLRLSTPV TAKAETTLFS TSVDTVTPST 
HTLVCSKPPP DNIPPASSTH VISTTSTPEA TQPISQVEET STYALSFPYT FSGGGVVASL 
ATGTTETSVV DETTPSHISA NKLTTSVNSH ISSSATYRVH TPVSIQLVTS TSVLSSDKDQ 
MTISLGKTPR TMEVTEMSPS KNSFISYSRG TPSLEMTDTG FPETTKISSH QTHSPSEIPL 
GTPSDGNLAS SPTSGSTQIT PTLTSSNTVG VHIPEMSTSL GKTALPSQAL TITTFLCPEK 
ESTSALPAYT PRTVEMIVNS TYVTHSVSYG QDTSFVDTTT SSSTRISNPM DINTTFSHLH 
SLRTQPEVTS VASFISESTQ TFPESLSLST AGLYNDGFTV LSDRITTAFS VPNVPTMLPR 
ESSMATSTPI YQMSSLPVNV TAFTSKKVSD TPPIVITKSS KTMHPGCLKS PCTATSGPMS 
EMSSIPVNNS AFTPATVSSD TSTRVGLFST LLSSVTPRTT MTMQTSTLDV TPVIYAGATS 
KNKMVSSAFT TEMIEAPSRI TPTTFLSPTE PTLPFVKTVP TTIMAGIVTP FVGTTAFSPL 
SSKSTGAISS IPKTTFSPFL SATQQSSQAD EATTLGILSG ITNRSLSTVN SGTGVALTDT 
YSRITVPENM LSPTHADSLH TSFNIQVSPS LTSFKSASGP TKNVKTTTNC FSSNTRKMTS 
LLEKTSLTNY ATSLNTPVSY PPWTPSSATL PSLTSFVYSP HSTEAEISTP KTSPPPTSQM 
VEFPVLGTRM TSSNTQPLLM TSWNIPTAEG SQFPISTTIN VPTSNEMETE TLHLVPGPLS 
TFTASQTGLV SKDVMAMSSI PMSGILPNHG LSENPSLSTS LRAITSTLAD VKHTFEKMTT 
SVTPGTTLPS ILSGATSGSV ISKSPILTWL LSSLPSGSPP ATVSNAPHVM TSSTVEVSKS 
TFLTSDMISA HPFTNLTTLP SATMSTILTR TIPTPTLGGI TTGFPTSLPM SINVTDDIVY 
ISTHPEASSR TTITANPRTV SHPSSFSRKT MSPSTTDHTL SVGAMPLPSS TITSSWNRIP 
TASSPSTLII PKPTLDSLLN IMTTTSTVPG ASFPLISTGV TYPFTATVSS PISSFFETTW 
LDSTPSFLST EASTSPTATK STVSFYNVEM SFSVFVEEPR IPITSVINEF TENSLNSIFQ 
NSEFSLATLE TQIKSRDISE EEMVMDRAIL EQREGQEMAT ISYVPYSCVC QVIIKASSSL 
ASSELMRKIK SKIHGNFTHG NFTQDQLTLL VNCEHVAVKK LEPGNCKADE TASKYKGTYK 
WLLTNPTETA QTRCIKNEDG NATRFCSISI NTGKSQWEKP KFKQCKLLQE LPDKIVDLAN 
ITISDENAED VAEHILNLIN ESPALGKEET KIIVSKISDI SQCDEISMNL THVMLQIINV 
VLEKQNNSAS DLHEISNEIL RIIERTGHKM EFSGQIANLT VAGLALAVLR GDHTFDGMAF 
SIHSYEEGTD PEIFLGNVPV GGILASIYLP KSLTERIPLS NLQTILFNFF GQTSLFKTKN 
VTKALTTYVV SASISDDMFI QNLADPVVIT LQHIGGNQNY GQVHCAFWDF ENNNGLGGWN 
SSGCKVKETN VNYTICQCDH LTHFGVLMDL SRSTVDSVNE QILALITYTG CGISSIFLGV 
AVVTYIAFHK LRKDYPAKIL INLCTALLML NLVFLINSWL SSFQKVGVCI TAAVALHYFL 
LVSFTWMGLE AVHMYLALVK VFNIYIPNYI LKFCLVGWGI PAIMVAITVS VKKDLYGTLS 
PTTPFCWIKD DSIFYISVVA YFCLIFLMNL SMFCTVLVQL NSVKSQIQKT RRKMILHDLK 
GTMSLTFLLG LTWGFAFFAW GPMRNFFLYL FAIFNTLQGF FIFVFHCVMK ESVREQWQIH 
LCCGWLRLDN SSDGSSRCQI KVGYKQEGLK KIFEHKLLTP SLKSTATSST FKSLGSAQGT 
PSEISFPNDD FDKDPYCSSP