Details for: ADCY8

Gene ID: 114

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: ADCY8

Ensembl ID: ENSG00000155897

Description: adenylate cyclase 8

Cell Significance Landscape

Associated with

Significant Cells

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

  • pvalb GABAergic cortical interneuron CL4023018
    CSI 52.23
    rCSI 64.97%
    PRS 95.16
  • sst GABAergic cortical interneuron CL4023017
    CSI 41.23
    rCSI 53.16%
    PRS 96.24
  • interneuron CL0000099
    CSI 36.23
    rCSI 72.75%
    PRS 97.29
  • retinal ganglion cell CL0000740
    CSI 26.86
    rCSI 59.33%
    PRS 95.63
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 22.44
    rCSI 70.17%
    PRS 96.26
  • macroglial cell CL0000126
    CSI 20.75
    rCSI 53.33%
    PRS 96.76
  • GABAergic amacrine cell CL4030027
    CSI 19.43
    rCSI 66.56%
    PRS 93.48
  • ependymal cell CL0000065
    CSI 18.81
    rCSI 38.17%
    PRS 92.52
  • VIP GABAergic cortical interneuron CL4023016
    CSI 18.36
    rCSI 21.93%
    PRS 95.72
  • glycinergic amacrine cell CL4030028
    CSI 17.82
    rCSI 46.43%
    PRS 95.59
  • pulmonary alveolar type 2 cell CL0002063
    CSI 16.35
    rCSI 25.36%
    PRS 98.65
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 16.3
    rCSI 28.79%
    PRS 95.78
  • inhibitory interneuron CL0000498
    CSI 16.19
    rCSI 37.38%
    PRS 95.93
  • amacrine cell CL0000561
    CSI 16.06
    rCSI 46.55%
    PRS 95.89
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 15.91
    rCSI 26.7%
    PRS 96.03
  • astrocyte of the cerebral cortex CL0002605
    CSI 15.73
    rCSI 35.26%
    PRS 95.78
  • sncg GABAergic cortical interneuron CL4023015
    CSI 14.03
    rCSI 22.56%
    PRS 95.62
  • neuron CL0000540
    CSI 13.98
    rCSI 37.23%
    PRS 93.34
  • serotonergic neuron CL0000850
    CSI 13.1
    rCSI 58.5%
    PRS 92.13
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 11.92
    rCSI 25.86%
    PRS 93.55
  • mature astrocyte CL0002627
    CSI 10.23
    rCSI 43.46%
    PRS 96.18
  • glioblast CL0000030
    CSI 10.04
    rCSI 16.02%
    PRS 96.38
  • parietal epithelial cell CL1000452
    CSI 8.89
    rCSI 23.77%
    PRS 97.64
  • glutamatergic neuron CL0000679
    CSI 8.58
    rCSI 17.64%
    PRS 93.58
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 8.49
    rCSI 30.57%
    PRS 95.03
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 8.44
    rCSI 20.51%
    PRS 94.57
  • L6b glutamatergic cortical neuron CL4023038
    CSI 8.33
    rCSI 26.05%
    PRS 95.84
  • dopaminergic neuron CL0000700
    CSI 8.18
    rCSI 46.21%
    PRS 94.71
  • GABAergic neuron CL0000617
    CSI 7.41
    rCSI 24.84%
    PRS 93.32
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 6.43
    rCSI 21.13%
    PRS 94.07
  • cerebellar granule cell CL0001031
    CSI 6.41
    rCSI 9.43%
    PRS 96.65
  • cerebellar neuron CL1001611
    CSI 5.59
    rCSI 49.22%
    PRS 93.5
  • basket cell CL0000118
    CSI 5.39
    rCSI 33.77%
    PRS 89.78
  • ON parasol ganglion cell CL4033052
    CSI 4.97
    rCSI 70.53%
    PRS 95.13
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 4.35
    rCSI 25.64%
    PRS 95.34
  • central nervous system neuron CL2000029
    CSI 4.22
    rCSI 31.04%
    PRS 96.23
  • diffuse bipolar 1 cell CL4033027
    CSI 4.22
    rCSI 31.72%
    PRS 93.14
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 3.6
    rCSI 6.55%
    PRS 96.37
  • ON midget ganglion cell CL4033046
    CSI 3.54
    rCSI 72.04%
    PRS 95.2
  • OFF midget ganglion cell CL4033047
    CSI 3.5
    rCSI 71.25%
    PRS 95.18
  • Bergmann glial cell CL0000644
    CSI 3.31
    rCSI 4.52%
    PRS 96.11
  • diffuse bipolar 3b cell CL4033030
    CSI 2.46
    rCSI 16.36%
    PRS 95.01
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.73
    rCSI 2.77%
    PRS 95.24

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 [ADCY8](/details-gene/114) encodes adenylate cyclase 8, a membrane-bound enzyme that catalyzes the synthesis of cyclic AMP (cAMP) from ATP. As a key second messenger, cAMP mediates numerous physiological processes. [ADCY8](/details-gene/114) is distinguished by its sensitivity to calcium and calmodulin, placing it at the intersection of calcium and cAMP signaling pathways. **Overall**, expression data reveals that [ADCY8](/details-gene/114) is a highly significant gene in the central nervous system, with particularly strong expression in specific subpopulations of inhibitory interneurons, such as [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)s and [sst GABAergic cortical interneuron](/details-cell/CL4023017)s. This specific expression pattern, combined with its involvement in processes like [synaptic plasticity](/details-ontology/GO:0031915) and [learning or memory](/details-ontology/GO:0007611), suggests it plays a critical role in modulating neural circuit function and cognitive processes. The gene is clinically associated with OMIM entry [103070](https://omim.org/entry/103070). ## Cellular Roles and Expression Landscape The expression profile of [ADCY8](/details-gene/114) underscores its specialized function within the nervous system. The gene shows the highest significance in various types of [interneuron](/details-cell/CL0000099)s, including [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 52.23), [sst GABAergic cortical interneuron](/details-cell/CL4023017) (CSI: 41.23), and [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 18.36). These cells are fundamental to regulating the excitability and information processing of cortical circuits. Beyond the cortex, [ADCY8](/details-gene/114) is also a key gene in the retina, with high significance in [retinal ganglion cell](/details-cell/CL0000740) (CSI: 26.86) and different types of [amacrine cell](/details-cell/CL0000561)s. This pattern suggests a conserved role in processing sensory information in complex neural networks. Additionally, its expression in [macroglial cell](/details-cell/CL0000126)s (CSI: 20.75) and [ependymal cell](/details-cell/CL0000065)s (CSI: 18.81) indicates a broader involvement in CNS homeostasis and signaling beyond direct neurotransmission. The consistent and high significance of [ADCY8](/details-gene/114) in these specific neuronal and glial subtypes establishes it as a critical component for specialized cellular functions within the brain and eye. ## Pathways and Molecular Function The molecular functions and pathway involvements of [ADCY8](/details-gene/114) are highly consistent with its cellular expression profile. As its name implies, its core molecular function is [adenylate cyclase activity](/details-ontology/GO:0004016), specifically [calcium- and calmodulin-responsive adenylate cyclase activity](/details-ontology/GO:0008294). This function is central to many signaling cascades, particularly the [Adenylate cyclase activating pathway](/details-ontology/R-HSA-170660) and broader [Gpcr downstream signalling](/details-ontology/R-HSA-388396) events. Its localization to cellular components like the [plasma membrane](/details-ontology/GO:0005886), [dendrite](/details-ontology/GO:0030425), [axon](/details-ontology/GO:0030424), and specifically to synaptic structures such as the [postsynaptic density](/details-ontology/GO:0014069) and [presynaptic membrane](/details-ontology/GO:0042734), positions it perfectly to respond to signals at the synapse. This is reflected in its deep involvement in neuronal processes, including [Transmission across chemical synapses](/details-ontology/R-HSA-112315) and [Neurotransmitter receptors and postsynaptic signal transmission](/details-ontology/R-HSA-112314). Functionally, this translates to roles in higher-order processes like [learning or memory](/details-ontology/GO:0007611) and the [positive regulation of long-term synaptic potentiation](/details-ontology/GO:1900273), suggesting it is a key molecular switch for activity-dependent changes in synaptic strength. Additionally, its participation in pathways like [glucose homeostasis](/details-ontology/GO:0042593) ([Link](https://doi.org/10.1007/s00125-014-3445-z)) and [neuroinflammatory response](/details-ontology/GO:0150076) hints at a role in linking metabolic state and inflammation to CNS function. ## Research Directions The specific expression of [ADCY8](/details-gene/114) in distinct neuronal subtypes and its function as a calcium-sensitive signal transducer present several compelling avenues for future research. **Proposed Hypotheses:** 1. **Modulation of Inhibitory Circuits:** Given its high significance in [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)s and its role in synaptic plasticity, [ADCY8](/details-gene/114) may function as a critical transducer that couples neuronal firing rates (via intracellular calcium) to the long-term tuning of inhibitory synaptic output. Dysregulation of [ADCY8](/details-gene/114) in these interneurons could disrupt the excitatory/inhibitory balance in the cortex, contributing to pathologies such as epilepsy or schizophrenia. 2. **Neuro-Metabolic Coupling:** The gene's established role in [glucose homeostasis](/details-ontology/GO:0042593) and its significant expression in [macroglial cell](/details-cell/CL0000126)s suggest that [ADCY8](/details-gene/114) could act as a sensor that links systemic metabolic changes to glial support functions and neuroinflammation within the CNS. This connection may be particularly relevant in understanding the neurological consequences of metabolic diseases like diabetes. **Key Experiment:** To test the hypothesis that [ADCY8](/details-gene/114) modulates inhibitory circuits, a cell-type-specific knockout approach would be highly informative. One could cross a mouse line containing a floxed *Adcy8* allele with a Pvalb-Cre driver line to specifically delete the gene only in [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)s. Subsequent ex vivo electrophysiological recordings from cortical slices could be used to assess changes in both short-term and long-term synaptic plasticity at the inhibitory synapses these neurons form. Behavioral assays assessing sensorimotor gating or working memory could then link these circuit-level changes to cognitive function. **Therapeutic Potential:** As an enzyme, [ADCY8](/details-gene/114) is a potentially druggable target. Its restricted expression, primarily within the CNS, could allow for targeted therapies for neurological and psychiatric disorders with fewer peripheral side effects. Small molecule activators of [ADCY8](/details-gene/114) could be investigated as cognitive enhancers or treatments for disorders associated with deficient cAMP signaling. Conversely, inhibitors might be explored for conditions characterized by neuronal hyperexcitability. However, the development of brain-penetrant modulators with high specificity for the ADCY8 isoform would be a critical prerequisite for any therapeutic strategy.

Genular Protein ID: 3797197339

Symbol: ADCY8_HUMAN

Name: ATP pyrophosphate-lyase 8

UniProtKB Accession Codes:

P40145

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 17 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EC 1 EMBL 2 Ensembl 1 ExpressionAtlas 1 GO 58 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 2 PIRSF 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 15 RefSeq 1 Rhea 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 8076676

Title: Molecular cloning of the human type VIII adenylyl cyclase.

PubMed ID: 8076676

DOI: 10.1016/0014-5793(94)00836-1

PubMed ID: 1715695

Title: Sequence of a human brain adenylyl cyclase partial cDNA: evidence for a consensus cyclase specific domain.

PubMed ID: 1715695

DOI: 10.1016/0006-291x(91)91392-p

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 25403481

Title: Multilevel control of glucose homeostasis by adenylyl cyclase 8.

PubMed ID: 25403481

DOI: 10.1007/s00125-014-3445-z

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 1251
  • Mass: 140122
  • Checksum: ABF25C40493E07C3
  • Sequence:
    • MELSDVRCLT GSEELYTIHP TPPAGDGRSA SRPQRLLWQT AVRHITEQRF IHGHRGGSGS 
GSGGSGKASD PAGGGPNHHA PQLSGDSALP LYSLGPGERA HSTCGTKVFP ERSGSGSASG 
SGGGGDLGFL HLDCAPSNSD FFLNGGYSYR GVIFPTLRNS FKSRDLERLY QRYFLGQRRK 
SEVVMNVLDV LTKLTLLVLH LSLASAPMDP LKGILLGFFT GIEVVICALV VVRKDTTSHT 
YLQYSGVVTW VAMTTQILAA GLGYGLLGDG IGYVLFTLFA TYSMLPLPLT WAILAGLGTS 
LLQVILQVVI PRLAVISINQ VVAQAVLFMC MNTAGIFISY LSDRAQRQAF LETRRCVEAR 
LRLETENQRQ ERLVLSVLPR FVVLEMINDM TNVEDEHLQH QFHRIYIHRY ENVSILFADV 
KGFTNLSTTL SAQELVRMLN ELFARFDRLA HEHHCLRIKI LGDCYYCVSG LPEPRQDHAH 
CCVEMGLSMI KTIRYVRSRT KHDVDMRIGI HSGSVLCGVL GLRKWQFDVW SWDVDIANKL 
ESGGIPGRIH ISKATLDCLN GDYNVEEGHG KERNEFLRKH NIETYLIKQP EDSLLSLPED 
IVKESVSSSD RRNSGATFTE GSWSPELPFD NIVGKQNTLA ALTRNSINLL PNHLAQALHV 
QSGPEEINKR IEHTIDLRSG DKLRREHIKP FSLMFKDSSL EHKYSQMRDE VFKSNLVCAF 
IVLLFITAIQ SLLPSSRVMP MTIQFSILIM LHSALVLITT AEDYKCLPLI LRKTCCWINE 
TYLARNVIIF ASILINFLGA ILNILWCDFD KSIPLKNLTF NSSAVFTDIC SYPEYFVFTG 
VLAMVTCAVF LRLNSVLKLA VLLIMIAIYA LLTETVYAGL FLRYDNLNHS GEDFLGTKEV 
SLLLMAMFLL AVFYHGQQLE YTARLDFLWR VQAKEEINEM KELREHNENM LRNILPSHVA 
RHFLEKDRDN EELYSQSYDA VGVMFASIPG FADFYSQTEM NNQGVECLRL LNEIIADFDE 
LLGEDRFQDI EKIKTIGSTY MAVSGLSPEK QQCEDKWGHL CALADFSLAL TESIQEINKH 
SFNNFELRIG ISHGSVVAGV IGAKKPQYDI WGKTVNLASR MDSTGVSGRI QVPEETYLIL 
KDQGFAFDYR GEIYVKGISE QEGKIKTYFL LGRVQPNPFI LPPRRLPGQY SLAAVVLGLV 
QSLNRQRQKQ LLNENNNTGI IKGHYNRRTL LSPSGTEPGA QAEGTDKSDL P

Genular Protein ID: 1286591004

Symbol: Q4F7X0_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q4F7X0

Database IDs:

ARBA 10 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 12 ChiTaRS 1 DNASU 1 DisGeNET 1 EC 1 EMBL 2 GO 7 Gene3D 1 InterPro 6 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRNR 1 PIRSF 1 PIRSR 1 PROSITE 3 PeptideAtlas 1 Pfam 3 PharmGKB 1 RefSeq 1 Rhea 1 RuleBase 1 SAM 2 SMART 1 SUPFAM 1

Sequence Information:

  • Length: 1120
  • Mass: 124842
  • Checksum: 618E235C2AB002C2
  • Sequence:
    • MELSDVRCLT GSEELYTIHP TPPAGDGRSA SRPQRLLWQT AVRHITEQRF IHGHRGGSGS 
GSGGSGKASD PAGGGPNHHA PQLSGDSALP LYSLGPGERA HSTCGTKVFP ERSGSGSASG 
SGGGGDLGFL HLDCAPSNSD FFLNGGYSYR GVIFPTLRNS FKSRDLERLY QRYFLGQRRK 
SEVVMNVLDV LTKLTLLVLH LSLASAPMDP LKGILLGFFT GIEVVICALV VVRKDTTSHT 
YLQYSGVVTW VAMTTQILAA GLGYGLLGDG IGYVLFTLFA TYGMLPLPLT WAILAGLGTS 
LLQVILQVVI PRLAVISINR VVAQAVLFMC MNTAGIFISY LSDRAQRQAF LETRRCVEAR 
LRLETENQRQ ERLVLSVLPR FVVLEMINDM TNVEDGHLQH QFHRIYIHRY ENVSILFADV 
KGFTNLSATL SAQELVRMLN ELFARFDRLV HEHHCLRIKI LGDCYYCVSG LPEPRQDHAH 
CCVEMGLSMI KTIRYVRSRT KHDVDMRIGI HSGSVLCGVL GLRKWQFDVW SWDVDIANKL 
ESGGIPGRIH ISEATLDCLN GDYNVEEGHG KERNEFLGKH NIETYLIKQP EDSLLSLPED 
IVKESVSSSD RRNSGATFTE GSWSPELPFD NIVGKQNTLA ALTRNSINLL PNHLAQALHV 
QSGPEEINKR IEHTIDLRSG DKLRREHIKP FSLMFKDSSL EHKYFVFTGV LAMVTCAVFL 
RLNSVLKLAV LLIMIAIYAP LTETVYAGLF LRYDNLNHSG EDFLGTKEVS LLLMAMFLLA 
VFYHGQQLEY TARLDFLWRV QAKEEINEMK ELREHNENML RNILPSHVAR HFLEKDQDNE 
ELYSQSYDAV GVMFASIPGF ADFYSQTEMN NQGVECLRLL NEIIADFDEL LGEDRFQDIE 
KIKTIGSTYM AVSGPSPEKQ QCEDKWGHLC ALADFSLALT ESIQEINKHS FNNFELRIGI 
SHGSVVAGVI GAKKPQYDIW GKTVNLASRM DSTGVSGRIQ VPEETYLILK DQGFAFDYRG 
EIYVKGISEQ EGKIKTYFLL GRVQPNPFIL PPRILPGQYS LAAVVLGLVQ SLNRQGQKQL 
LNENNNTGII KGHYNRRTLL SPSGTEPGAQ AEGTDKSDLP