Details for: AMPD2

Gene ID: 271

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: AMPD2

Ensembl ID: ENSG00000116337

Description: adenosine monophosphate deaminase 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mesodermal cell CL0000222
    CSI 6.62
    rCSI 7.95%
    PRS 79.21
  • Kupffer cell CL0000091
    CSI 5.39
    rCSI 12.32%
    PRS 81.95
  • pancreatic D cell CL0000173
    CSI 3.35
    rCSI 3.3%
    PRS 83.58
  • intermediate monocyte CL0002393
    CSI 3.34
    rCSI 5.04%
    PRS 86.03
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.32
    rCSI 5.86%
    PRS 63
  • rod bipolar cell CL0000751
    CSI 3.24
    rCSI 5.82%
    PRS 74.64
  • common myeloid progenitor CL0000049
    CSI 3.12
    rCSI 2.52%
    PRS 83.24
  • CD4-positive helper T cell CL0000492
    CSI 3.07
    rCSI 2.33%
    PRS 92.06
  • basal cell CL0000646
    CSI 3.06
    rCSI 4.09%
    PRS 79.48
  • promyelocyte CL0000836
    CSI 2.86
    rCSI 4.13%
    PRS 86.37
  • retina horizontal cell CL0000745
    CSI 2.77
    rCSI 4.22%
    PRS 78.03
  • myeloid leukocyte CL0000766
    CSI 2.73
    rCSI 2.52%
    PRS 82.67
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.72
    rCSI 2.77%
    PRS 89.94
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.69
    rCSI 2.07%
    PRS 83.96
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.65
    rCSI 3.47%
    PRS 90.83
  • early lymphoid progenitor CL0000936
    CSI 2.62
    rCSI 2.3%
    PRS 85.89
  • OFF-bipolar cell CL0000750
    CSI 2.61
    rCSI 3.57%
    PRS 82.8
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.57
    rCSI 3.32%
    PRS 64.77
  • retinal cone cell CL0000573
    CSI 2.57
    rCSI 4.14%
    PRS 71.53
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.53
    rCSI 5.68%
    PRS 64.44
  • retinal pigment epithelial cell CL0002586
    CSI 2.51
    rCSI 4.99%
    PRS 76.93
  • chondrocyte CL0000138
    CSI 2.51
    rCSI 3.99%
    PRS 74.54
  • hematopoietic stem cell CL0000037
    CSI 2.5
    rCSI 1.66%
    PRS 83.73
  • elicited macrophage CL0000861
    CSI 2.41
    rCSI 2.22%
    PRS 88.26
  • ON-bipolar cell CL0000749
    CSI 2.36
    rCSI 3.51%
    PRS 80.97
  • lung macrophage CL1001603
    CSI 2.3
    rCSI 5.14%
    PRS 87.82
  • hepatocyte CL0000182
    CSI 2.28
    rCSI 4.09%
    PRS 80.55
  • pancreatic A cell CL0000171
    CSI 2.18
    rCSI 2.29%
    PRS 84.23
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.17
    rCSI 2.59%
    PRS 63.73
  • choroid plexus epithelial cell CL0000706
    CSI 2.13
    rCSI 3.49%
    PRS 70.95
  • enteroendocrine cell CL0000164
    CSI 1.96
    rCSI 2.68%
    PRS 80.77
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.92
    rCSI 3.49%
    PRS 72.91
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.91
    rCSI 3.21%
    PRS 63.55
  • extravillous trophoblast CL0008036
    CSI 1.9
    rCSI 2.35%
    PRS 79.3
  • inhibitory interneuron CL0000498
    CSI 1.76
    rCSI 4.06%
    PRS 69.39
  • CD14-positive monocyte CL0001054
    CSI 1.75
    rCSI 2.18%
    PRS 89.45
  • group 3 innate lymphoid cell CL0001071
    CSI 1.73
    rCSI 1.3%
    PRS 86.5
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.68
    rCSI 2.09%
    PRS 61.51
  • Langerhans cell CL0000453
    CSI 1.65
    rCSI 2.53%
    PRS 90.97
  • amacrine cell CL0000561
    CSI 1.63
    rCSI 4.72%
    PRS 70.99
  • retinal bipolar neuron CL0000748
    CSI 1.62
    rCSI 3.03%
    PRS 69.79
  • mononuclear phagocyte CL0000113
    CSI 1.56
    rCSI 3.44%
    PRS 84.69
  • platelet CL0000233
    CSI 1.55
    rCSI 6.45%
    PRS 78.47
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.53
    rCSI 1.33%
    PRS 84.88
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.3
    rCSI 1.18%
    PRS 79.28
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.16
    rCSI 1.87%
    PRS 65.14
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.05
    rCSI 1.26%
    PRS 88.12
  • type B pancreatic cell CL0000169
    CSI 1.03
    rCSI 2.27%
    PRS 80.51
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.87
    rCSI 2.11%
    PRS 61.58
  • megakaryocyte CL0000556
    CSI 0.79
    rCSI 3.44%
    PRS 85.94
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.77
    rCSI 4.68%
    PRS 91.18
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.76
    rCSI 2.38%
    PRS 67.62
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.71
    rCSI 2.23%
    PRS 65.26
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.66
    rCSI 2.5%
    PRS 64.16
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.55
    rCSI 1.98%
    PRS 61.55
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.28
    rCSI 6.7%
    PRS 62.34

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 [AMPD2](/details-gene/271) encodes adenosine monophosphate (AMP) deaminase 2, a cytosolic enzyme crucial for purine metabolism. This enzyme catalyzes the deamination of AMP to inosine monophosphate (IMP), thereby playing a key role in regulating cellular energy charge and nucleotide pools. Its function is integral to processes such as the [AMP metabolic process](/details-gene/GO:0046033) and [purine salvage](/details-gene/R-HSA-74217). Expression data indicates its significance across a diverse range of cell types, with particularly high levels in cells of mesodermal origin, including various immune cells like [Kupffer cell](/details-cell/CL0000091) and monocytes. Clinically, mutations in [AMPD2](/details-gene/271) are associated with a neurodegenerative disorder ([OMIM [102771](https://omim.org/entry/102771)]), highlighting its importance in maintaining GTP synthesis and neuronal homeostasis ([Link](https://doi.org/10.1016/j.cell.2013.07.005)). ## Cellular Roles and Expression Landscape The expression profile of [AMPD2](/details-gene/271) suggests a fundamental role in cellular metabolism across multiple tissues, with pronounced significance in specific lineages. **Overall**, the gene shows its highest significance in [mesodermal cell](/details-cell/CL0000222), indicating a broad function in cells derived from this germ layer. A more detailed analysis reveals a strong enrichment in the myeloid lineage of the immune system. It is a highly significant gene in tissue-resident macrophages like [Kupffer cell](/details-cell/CL0000091) and in circulating monocytes, including [intermediate monocyte](/details-cell/CL0002393), [CD14-low, CD16-positive monocyte](/details-cell/CL0002396), and [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397). Its importance is also evident in myeloid progenitors, such as the [common myeloid progenitor](/details-cell/CL0000049) and [promyelocyte](/details-cell/CL0000836). This pattern suggests [AMPD2](/details-gene/271) is a key metabolic enzyme supporting the high energy and biosynthetic demands of myeloid cell development and function. Significance is also noted in the lymphoid lineage, including [CD4-positive helper T cell](/details-cell/CL0000492) and developing [double-positive, alpha-beta thymocyte](/details-cell/CL0000809). Beyond the immune system, [AMPD2](/details-gene/271) shows notable significance in specific, metabolically active cell types. These include endocrine cells like the [pancreatic D cell](/details-cell/CL0000173) and specialized neuronal cells of the retina ([rod bipolar cell](/details-cell/CL0000751), [retina horizontal cell](/details-cell/CL0000745)) and cortex ([caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064)). This diverse expression landscape underscores its role in maintaining cellular energy balance in a variety of physiological contexts. ## Pathways and Molecular Function The molecular functions of [AMPD2](/details-gene/271) are centered on nucleotide metabolism and cellular bioenergetics. As an enzyme with [AMP deaminase activity](/details-gene/GO:0003876), it is a central node in the [metabolism of nucleotides](/details-gene/R-HSA-15869) and is annotated to the broader [Metabolism](/details-gene/R-HSA-1430728) pathway. By converting AMP to IMP, it participates directly in the [IMP biosynthetic process](/details-gene/GO:0006188) and [IMP salvage](/details-gene/GO:0032264), which are critical for synthesizing purine nucleotides. This catalytic activity is fundamental to maintaining [energy homeostasis](/details-gene/GO:0097009) within the cell. The enzyme helps regulate the adenylate energy charge by removing AMP, which can accumulate under conditions of high ATP consumption. This function is likely vital for the highly active immune and neuronal cells where its expression is significant. Furthermore, its role in providing IMP for the synthesis of guanine nucleotides is critical, as deficiencies in [AMPD2](/details-gene/271) have been shown to impair GTP synthesis ([Link](https://doi.org/10.1016/j.cell.2013.07.005)). Consistent with its role as a metabolic enzyme, it is primarily located in the [cytosol](/details-gene/GO:0005829) and is known to engage in [protein binding](/details-gene/GO:0005515). ## Research Directions The widespread yet specific expression pattern of [AMPD2](/details-gene/271), coupled with its known role in a severe neurodegenerative disorder, opens several avenues for future research. ### Proposed Hypotheses: 1. **[AMPD2](/details-gene/271) is a critical metabolic checkpoint for myeloid cell activation.** Given its high significance in monocytes and Kupffer cells, it is hypothesized that [AMPD2](/details-gene/271) activity is dynamically regulated during inflammation to control the balance of ATP and GTP pools, which are essential for powering phagocytosis, cytokine production, and migratory responses. 2. **The function of [AMPD2](/details-gene/271) is essential for maintaining the viability and function of high-energy demand neurons.** Its notable expression in specific neuronal subtypes ([rod bipolar cell](/details-cell/CL0000751), interneurons) suggests that it plays a specialized role in preventing excitotoxicity or metabolic collapse by managing local nucleotide pools required for sustained neurotransmission. ### Key Experimental Approach: To test the first hypothesis regarding the role of [AMPD2](/details-gene/271) in myeloid cell function, a targeted knockout of the gene could be generated in a human monocyte-like cell line (e.g., THP-1) using CRISPR-Cas9. These knockout cells, along with wild-type controls, would be differentiated into macrophages and stimulated with an inflammatory agent like lipopolysaccharide (LPS). The functional consequences would be assessed by measuring phagocytic capacity (e.g., via flow cytometry with fluorescent beads), quantifying cytokine secretion profiles using an ELISA or multiplex bead array, and performing metabolomic analysis via liquid chromatography-mass spectrometry (LC-MS) to directly measure the changes in ATP, ADP, AMP, and GTP pools post-stimulation. ### Therapeutic Potential: [AMPD2](/details-gene/271) represents a compelling therapeutic target, primarily in the context of the neurodegenerative disorder caused by its deficiency ([OMIM [102771](https://omim.org/entry/102771)]). Research indicates that this disorder is caused by loss-of-function mutations that impair GTP synthesis ([Link](https://doi.org/10.1016/j.cell.2013.07.005)). Therefore, therapeutic strategies would likely focus on **activation** or functional restoration rather than inhibition. The development of small-molecule pharmacological chaperones to stabilize misfolded mutant protein or allosteric activators to boost the activity of the remaining functional enzyme could be viable approaches. Gene therapy to restore [AMPD2](/details-gene/271) expression in affected neuronal populations may also represent a long-term therapeutic option.

Genular Protein ID: 610447293

Symbol: AMPD2_HUMAN

Name: AMP deaminase isoform L

UniProtKB Accession Codes:

Q01433 A0A5F9UK94 B4DK50 B4DZI5 E9PNG0 Q14856 Q14857 Q16686 Q16687 Q16688 Q16729 Q5T693 Q5T695 Q96IA1 Q9UDX8 Q9UDX9 Q9UMU4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChEBI 10 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 21 Ensembl 6 EvolutionaryTrace 1 ExpressionAtlas 1 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PIR 6 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 1 RefSeq 6 Rhea 1 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1429593

Title: Molecular cloning of AMP deaminase isoform L. Sequence and bacterial expression of human AMPD2 cDNA.

PubMed ID: 1429593

DOI: 10.1016/s0021-9258(18)41686-9

PubMed ID: 8526848

Title: Characterization of human AMP deaminase 2 (AMPD2) gene expression reveals alternative transcripts encoding variable N-terminal extensions of isoform L.

PubMed ID: 8526848

DOI: 10.1042/bj3120401

PubMed ID: 8764830

Title: Cloning, sequence and characterization of the human AMPD2 gene: evidence for transcriptional regulation by two closely spaced promoters.

PubMed ID: 8764830

DOI: 10.1016/0167-4781(96)00089-9

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 18088087

Title: Phosphoproteome of resting human platelets.

PubMed ID: 18088087

DOI: 10.1021/pr0704130

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23911318

Title: AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder.

PubMed ID: 23911318

DOI: 10.1016/j.cell.2013.07.005

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 24482476

Title: Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.

PubMed ID: 24482476

DOI: 10.1126/science.1247363

Sequence Information:

  • Length: 825
  • Mass: 94890
  • Checksum: F79EAD41CBA771AC
  • Sequence:
    • MASYPSGSGK PKAKYPFKKR ASLQASTAAP EARGGLGAPP LQSARSLPGP APCLKHFPLD 
LRTSMDGKCK EIAEELFTRS LAESELRSAP YEFPEESPIE QLEERRQRLE RQISQDVKLE 
PDILLRAKQD FLKTDSDSDL QLYKEQGEGQ GDRSLRERDV LEREFQRVTI SGEEKCGVPF 
TDLLDAAKSV VRALFIREKY MALSLQSFCP TTRRYLQQLA EKPLETRTYE QGPDTPVSAD 
APVHPPALEQ HPYEHCEPST MPGDLGLGLR MVRGVVHVYT RREPDEHCSE VELPYPDLQE 
FVADVNVLMA LIINGPIKSF CYRRLQYLSS KFQMHVLLNE MKELAAQKKV PHRDFYNIRK 
VDTHIHASSC MNQKHLLRFI KRAMKRHLEE IVHVEQGREQ TLREVFESMN LTAYDLSVDT 
LDVHADRNTF HRFDKFNAKY NPIGESVLRE IFIKTDNRVS GKYFAHIIKE VMSDLEESKY 
QNAELRLSIY GRSRDEWDKL ARWAVMHRVH SPNVRWLVQV PRLFDVYRTK GQLANFQEML 
ENIFLPLFEA TVHPASHPEL HLFLEHVDGF DSVDDESKPE NHVFNLESPL PEAWVEEDNP 
PYAYYLYYTF ANMAMLNHLR RQRGFHTFVL RPHCGEAGPI HHLVSAFMLA ENISHGLLLR 
KAPVLQYLYY LAQIGIAMSP LSNNSLFLSY HRNPLPEYLS RGLMVSLSTD DPLQFHFTKE 
PLMEEYSIAT QVWKLSSCDM CELARNSVLM SGFSHKVKSH WLGPNYTKEG PEGNDIRRTN 
VPDIRVGYRY ETLCQELALI TQAVQSEMLE TIPEEAGITM SPGPQ