Details for: ADSS1

Gene ID: 122622

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: ADSS1

Ensembl ID: ENSG00000185100

Description: adenylosuccinate synthase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • muscle cell CL0000187
    CSI 4.82
    rCSI 9.89%
    PRS 98.05
  • ciliated epithelial cell CL0000067
    CSI 3.19
    rCSI 2.8%
    PRS 96.23
  • Mueller cell CL0000636
    CSI 3.16
    rCSI 7.2%
    PRS 96.98
  • epithelial cell CL0000066
    CSI 2.65
    rCSI 4.07%
    PRS 94.57
  • lung ciliated cell CL1000271
    CSI 2.64
    rCSI 3.05%
    PRS 97.19
  • ciliated cell CL0000064
    CSI 2.6
    rCSI 4.21%
    PRS 96.4
  • cardiac muscle cell CL0000746
    CSI 2.47
    rCSI 3.55%
    PRS 96.26
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.09
    rCSI 2.48%
    PRS 96.04

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [ADSS1](/details-gene/122622) (Adenylosuccinate Synthetase 1) is a protein-coding gene located on chromosome 14q32.33. It encodes a key enzyme in the *de novo* purine biosynthesis pathway, which is critical for the production of adenosine monophosphate (AMP). This enzyme, also known as AdSSL1, is an isoform primarily expressed in muscle tissue. The expression data underscores this, showing its highest significance in [muscle cell](/details-cell/CL0000187), particularly [cardiac muscle cell](/details-cell/CL0000746). Consistent with this, mutations in [ADSS1](/details-gene/122622) have been linked to autosomal recessive adolescent-onset distal myopathy, highlighting its essential role in maintaining muscle function and energy homeostasis [Link](https://doi.org/10.1002/ana.24550). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ADSS1](/details-gene/122622) demonstrates a highly specialized role, with its significance being most pronounced in tissues with high metabolic demands. The gene is a dominant marker for contractile cells, showing the highest significance score in [muscle cell](/details-cell/CL0000187) (CSI: 4.82) and significant expression in [cardiac muscle cell](/details-cell/CL0000746) (CSI: 2.47). This is consistent with its initial characterization as a novel muscle adenylosuccinate synthetase [Link](https://doi.org/10.1007/s11010-005-2539-9) and aligns with the high energy requirements of muscle contraction, which depends on robust purine nucleotide pools for ATP and GTP synthesis. A secondary but notable expression pattern is observed in various types of ciliated cells. [ADSS1](/details-gene/122622) shows high significance in [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 3.19), [lung ciliated cell](/details-cell/CL1000271) (CSI: 2.64), [ciliated cell](/details-cell/CL0000064) (CSI: 2.60), and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL00002145) (CSI: 1.09). This suggests a role in supporting the energy-intensive process of ciliary movement, which is vital for functions like mucociliary clearance in the respiratory tract. The gene is also significant in [Mueller cell](/details-cell/CL0000636) of the retina (CSI: 3.16), a glial cell type with high metabolic activity essential for retinal homeostasis. ## Pathways and Molecular Function The molecular function of [ADSS1](/details-gene/122622) is well-defined. It possesses adenylosuccinate synthase activity ([GO:0004019](https://www.ebi.ac.uk/QuickGO/term/GO:0004019)), which catalyzes the first committed step in the synthesis of AMP from inosine monophosphate (IMP). This places it as a central enzyme in the AMP biosynthetic process ([GO:0006167](https://www.ebi.ac.uk/QuickGO/term/GO:0006167)) and the broader Reactome pathway of Purine ribonucleoside monophosphate biosynthesis ([R-HSA-73817](https://reactome.org/content/detail/R-HSA-73817)). Consistent with its catalytic mechanism, [ADSS1](/details-gene/122622) is annotated with GTP binding ([GO:0005525](https://www.ebi.ac.uk/QuickGO/term/GO:0005525)), magnesium ion binding ([GO:0000287](https://www.ebi.ac.uk/QuickGO/term/GO:0000287)), and phosphate ion binding ([GO:0042301](https://www.ebi.ac.uk/QuickGO/term/GO:0042301)). The protein is localized primarily to the [cytosol](/details-cell/GO:0005829), where these metabolic processes occur. Its involvement in the aspartate metabolic process ([GO:0006531](https://www.ebi.ac.uk/QuickGO/term/GO:0006531)) and glutamine metabolic process ([GO:0006541](https://www.ebi.ac.uk/QuickGO/term/GO:0006541)) reflects the substrate requirements for purine synthesis. This fundamental role in metabolism aligns with its high expression in metabolically active cells like muscle and ciliated cells. ## Research Directions The established link between [ADSS1](/details-gene/122622) loss-of-function mutations and myopathy provides a clear foundation for further investigation into its role in cellular energy homeostasis and disease pathology [Link](https://doi.org/10.1002/ana.24550). ### Testable Hypotheses 1. **Hypothesis 1: Energy Crisis in Muscle Pathophysiology.** We hypothesize that the myopathy associated with [ADSS1](/details-gene/122622) mutations stems from a chronic inability of muscle cells to replenish adenine nucleotide pools during periods of high metabolic stress (e.g., exercise), leading to an energy deficit, impaired contractility, and progressive muscle fiber damage. 2. **Hypothesis 2: Role in Ciliopathies.** Given its high significance in multiple ciliated cell types, we hypothesize that [ADSS1](/details-gene/122622) is critical for maintaining the high ATP levels required for dynein motor activity and ciliary beating. Its deficiency could therefore contribute to the spectrum of diseases known as ciliopathies, particularly those affecting the respiratory tract. ### Proposed Experiment To test the "Energy Crisis" hypothesis (Hypothesis 1), a conditional knockout mouse model with *Adss1* specifically deleted in skeletal muscle (*Adss1*-mKO) would be generated. These mice, along with wild-type littermates, would be subjected to a forced exercise regimen on a treadmill. The key readouts would include: * **Physiological Assessment:** Measurement of grip strength and endurance to quantify muscle function deficits. * **Metabolomic Analysis:** Targeted mass spectrometry on muscle tissue collected pre- and post-exercise to directly measure the levels of ATP, ADP, AMP, GTP, and IMP, to test for a failure to replenish the adenine pool. * **Histological Analysis:** Examination of muscle fiber morphology, central nucleation, and markers of damage (e.g., Evans Blue Dye uptake) to assess the pathological consequences of the energy deficit. ### Therapeutic Potential [ADSS1](/details-gene/122622) represents a potential therapeutic target for a specific, rare form of inherited myopathy. Since the disease is caused by a loss-of-function, the therapeutic goal would be to restore or augment its enzymatic activity. This rules out inhibitors and points towards strategies like gene replacement therapy. Delivering a functional copy of the [ADSS1](/details-gene/122622) gene via an adeno-associated virus (AAV) vector, particularly one with high muscle tropism (e.g., AAV9), could potentially correct the underlying metabolic defect in affected muscle cells. Small molecule activators are generally challenging to develop for enzymes of this class, making gene therapy a more promising long-term avenue for exploration.

Genular Protein ID: 3092991140

Symbol: PURA1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8N142 Q86TT6 Q8N714

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 22 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 9 EC 1 EMBL 5 Ensembl 3 ExpressionAtlas 1 GO 19 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 HAMAP 2 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 1 RefSeq 3 Rhea 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15786719

Title: Molecular cloning and characterization of a novel muscle adenylosuccinate synthetase, AdSSL1, from human bone marrow stromal cells.

PubMed ID: 15786719

DOI: 10.1007/s11010-005-2539-9

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 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: 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: 26506222

Title: ADSSL1 mutation relevant to autosomal recessive adolescent onset distal myopathy.

PubMed ID: 26506222

DOI: 10.1002/ana.24550

Sequence Information:

  • Length: 457
  • Mass: 50208
  • Checksum: 387341D49721B2EF
  • Sequence:
    • MSGTRASNDR PPGAGGVKRG RLQQEAAATG SRVTVVLGAQ WGDEGKGKVV DLLATDADII 
SRCQGGNNAG HTVVVDGKEY DFHLLPSGII NTKAVSFIGN GVVIHLPGLF EEAEKNEKKG 
LKDWEKRLII SDRAHLVFDF HQAVDGLQEV QRQAQEGKNI GTTKKGIGPT YSSKAARTGL 
RICDLLSDFD EFSSRFKNLA HQHQSMFPTL EIDIEGQLKR LKGFAERIRP MVRDGVYFMY 
EALHGPPKKI LVEGANAALL DIDFGTYPFV TSSNCTVGGV CTGLGIPPQN IGDVYGVVKA 
YTTRVGIGAF PTEQINEIGG LLQTRGHEWG VTTGRKRRCG WLDLMILRYA HMVNGFTALA 
LTKLDILDVL GEVKVGVSYK LNGKRIPYFP ANQEMLQKVE VEYETLPGWK ADTTGARRWE 
DLPPQAQNYI RFVENHVGVA VKWVGVGKSR ESMIQLF

Genular Protein ID: 2300518916

Symbol: B3KTV4_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KTV4

Database IDs:

ARBA 5 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 14 DNASU 1 DisGeNET 1 EC 1 EMBL 4 GO 5 Gene3D 2 HAMAP 1 HAMAP-Rule 1 InterPro 4 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 2 Rhea 1 SMART 1 SMR 1 SUPFAM 1 UniPathway 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 252
  • Mass: 28079
  • Checksum: FF8A9B0C036D24B8
  • Sequence:
    • MFPTLEIDIE GQLKRLKGFA ERIRPMVRDG VYFMYEALHG PPKKILVEGA NAALLDIDFG 
TYPFVTSSNC TVGGVCTGLG IPPQNIGDVY GVVKAYTTRV GIGAFPTEQI NEIGGLLQTR 
GHEWGVTTGR KRRCGWLDLM ILRYAHMVNG FTALALTKLD ILDVLGEVKV GVSYKLNGKR 
IPYFPANQEM LQKVEVEYET LPGWKADTTG ARRWEDLPPQ AQNYIRFVEN HVGVAVKWVG 
VGKSRESMIQ LF