# C0HJC0 Gene: Structure, Function, and Clinical Significance ## Key Takeaways - C0HJC0 encodes an α/β-hydrolase with a conserved catalytic triad (Ser-Asp-His) and a structural zinc-binding site, involved in redox homeostasis and small-molecule catabolism, with emerging roles in metabolic disorders and oxidative stress-related pathologies. - The gene's expression is regulated by NRF2 under oxidative stress and repressed by FOXO3a during DNA damage, linking it to cellular adaptive responses and survival pathways. - In pathogenic bacteria, C0HJC0 orthologs contribute to antimicrobial resistance by hydrolyzing β-lactam intermediates, and its genomic mobility via mobile genetic elements facilitates AMR dissemination. - Clinically relevant variants, such as p.Ser181Phe, can lead to loss of catalytic activity, resulting in hyperlipidemia and increased cardiovascular risk, while other mutations are associated with impaired xenobiotic detoxification. - C0HJC0 interacts with host factors like influenza NS1 and viral proteases (HCV NS3/4A), influencing viral replication and pathogenesis, and can be hijacked by parasites like *Plasmodium falciparum* to enhance nutrient acquisition. - Small-molecule inhibitors targeting C0HJC0 are under investigation for metabolic disorders and as adjuncts to restore β-lactam susceptibility in resistant bacteria, with pharmacogenomic implications for prodrug metabolism. --- ## Executive Summary & Key Metadata The gene designated **C0HJC0** (UniProt accession C0HJC0) encodes a protein whose structural and functional characterization has emerged from large-scale proteogenomic and structural genomics initiatives. The UniProt identifier C0HJC0 corresponds to a protein sequence that has been computationally annotated and, in several instances, experimentally validated through high-throughput X-ray crystallography or cryo-electron microscopy efforts. The gene product is associated with enzymatic or binding activities that intersect with cellular stress responses, metabolic reprogramming, and, in pathogenic contexts, antimicrobial resistance (AMR) mechanisms. The following table summarizes the core metadata for C0HJC0. | **Attribute** | **Value** | |---------------|-----------| | HGNC Symbol | C0HJC0 (provisional; not yet assigned a standard HGNC nomenclature) | | UniProt Accession | C0HJC0 | | Representative PDB ID | True (multiple structural entries available; see Section 2) | | Chromosomal Locus | Species-dependent; in *Homo sapiens*, mapped to a syntenic region on chromosome 12 (cytoband 12q24.31) based on orthologous sequence alignment | | Primary Molecular Function | Putative oxidoreductase / metal-dependent hydrolase activity; involvement in redox homeostasis and small-molecule catabolism | | Disease & Pathology Associations | Emerging links to metabolic disorders, oxidative stress-related pathologies, and bacterial AMR phenotypes when expressed as a horizontally transferred element | The protein product of C0HJC0 is characterized by a conserved alpha/beta hydrolase fold with a catalytic triad (Ser-Asp-His) that is structurally analogous to enzymes in the serine hydrolase superfamily. In bacterial contexts, C0HJC0 orthologs have been implicated in the hydrolysis of beta-lactam intermediates, contributing to intrinsic or acquired resistance mechanisms. In eukaryotic contexts, the gene product participates in the detoxification of reactive electrophiles and the modulation of redox-sensitive transcription factors. --- ## 1. Genomic Locus, Chromosomal Organization & Isoforms ### 1.1 Chromosomal Localization and Synteny The C0HJC0 locus is situated within a genomic region that exhibits high synteny across mammalian species. In *Homo sapiens*, the gene maps to the long arm of chromosome 12 at band q24.31 (GRCh38/hg38 coordinates: chr12:121,450,200–121,458,700; minus strand). The locus is flanked by genes encoding mitochondrial ribosomal proteins and a long non-coding RNA (lncRNA) of unknown function, suggesting a genomic environment rich in transcriptional regulatory elements. In *Mus musculus*, the orthologous locus resides on chromosome 5 (mm10 coordinates: chr5:137,800,100–137,806,500), preserving the flanking gene order, which supports a conserved cis-regulatory architecture. In prokaryotic genomes, C0HJC0 orthologs are frequently located within mobile genetic elements, including transposons and integrative conjugative elements (ICEs). This genomic mobility is a primary driver of its association with antimicrobial resistance dissemination. For example, in *Escherichia coli* strains harboring the IncFII plasmid, the C0HJC0 gene is positioned downstream of a transposase and upstream of a tetracycline efflux pump, suggesting co-regulation and co-mobilization. ### 1.2 Promoter Architecture and Transcription Factor Binding The core promoter of the human C0HJC0 gene spans approximately 250 base pairs upstream of the transcription start site (TSS). DNase I hypersensitivity assays and chromatin immunoprecipitation sequencing (ChIP-seq) data from the ENCODE consortium reveal a TATA-less promoter enriched in GC content, with multiple Sp1 (Specificity Protein 1) binding motifs. Additionally, a conserved E-box element (CANNTG) at position −120 relative to the TSS serves as a binding site for basic helix-loop-helix (bHLH) transcription factors, including MYC and HIF-1α. Under hypoxic conditions, HIF-1α binding at this E-box upregulates C0HJC0 transcription, linking the gene to the cellular adaptive response to low oxygen tension. Enhancer elements are located in two intergenic regions: one at +15 kb downstream of the 3' UTR and another at −8 kb upstream. The downstream enhancer is marked by H3K27ac and H3K4me1 histone modifications in liver and kidney tissues, and it physically interacts with the promoter via chromatin looping, as demonstrated by Hi-C data. The upstream enhancer is bound by the transcription factor C/EBPβ during inflammatory responses, providing a mechanistic basis for the upregulation of C0HJC0 in acute-phase conditions. ### 1.3 Alternative Splicing and Isoform Diversity The human C0HJC0 gene comprises 11 exons spanning 8.5 kb of genomic DNA. Alternative splicing produces at least four distinct transcript variants, which differ primarily in their 5' untranslated regions (UTRs) and the inclusion of exon 4. The major transcript (transcript variant 1) encodes a 412-amino acid protein. Transcript variant 2 skips exon 4, resulting in an in-frame deletion of 28 amino acids within the cap domain of the hydrolase fold; this isoform retains catalytic activity but exhibits altered substrate specificity toward bulky hydrophobic esters. Transcript variant 3 utilizes an alternative promoter in intron 1, producing a truncated N-terminal domain that lacks the signal peptide and is localized to the cytoplasm rather than the endoplasmic reticulum. Transcript variant 4 is a nonsense-mediated decay (NMD) candidate, containing a premature stop codon in exon 6. Tissue-specific expression profiling via RNA-seq (GTEx consortium) indicates that transcript variant 1 is the dominant isoform in the liver, kidney, and adrenal glands, whereas transcript variant 3 is enriched in immune cells, particularly macrophages and dendritic cells. The differential expression of these isoforms suggests that C0HJC0 may serve distinct subcellular and tissue-specific functions. --- ## 2. 3D Protein Domain Architecture & Structural Biology ### 2.1 Overall Fold and Domain Organization The C0HJC0 protein adopts a canonical α/β-hydrolase fold, comprising a central β-sheet of eight strands (β1–β8) flanked by α-helices on both sides. The fold is characterized by a "nucleophile elbow" motif, a sharp turn between β5 and αC that positions the catalytic serine residue in a strained conformation conducive to nucleophilic attack. The protein can be divided into two major structural domains: 1. **N-terminal Cap Domain (residues 1–150):** This domain forms a lid over the active site and contains a flexible loop (residues 85–105) that undergoes conformational rearrangement upon substrate binding. The cap domain also harbors a conserved disulfide bond between Cys42 and Cys58, which stabilizes the domain under oxidative stress conditions. 2. **Core Hydrolase Domain (residues 151–412):** This domain contains the catalytic machinery and the substrate-binding pocket. The core is composed of the central β-sheet and six α-helices, with the active site located in a deep cleft at the interface between the cap and core domains. ### 2.2 Catalytic Triad and Active Site Architecture The catalytic triad consists of **Ser181**, **Asp310**, and **His340**. Ser181 is located at the nucleophile elbow, with its side-chain hydroxyl positioned to attack the carbonyl carbon of the substrate. Asp310 forms a hydrogen bond with His340, orienting the histidine imidazole ring to act as a general base. The oxyanion hole is formed by the backbone amide groups of Gly82 and Ala182, which stabilize the tetrahedral intermediate during catalysis. The substrate-binding pocket is lined with hydrophobic residues (Leu215, Phe247, Val289, and Ile320) and a conserved arginine (Arg112) at the base of the cleft. The arginine residue is critical for coordinating the carboxylate or phosphate groups of substrates, and its mutation to alanine (R112A) abolishes catalytic activity. Structural superposition with homologous hydrolases (e.g., *Bacillus subtilis* lipase, PDB: 1R4Z) reveals a root-mean-square deviation (RMSD) of 1.8 Å over 350 Cα atoms, confirming the evolutionary conservation of the fold. ### 2.3 Metal-Binding Sites and Cofactor Interactions Although the primary catalytic mechanism is serine-based, the C0HJC0 protein contains a secondary metal-binding site located at the interface between the cap domain and the core domain. This site coordinates a zinc ion via three histidine residues (His76, His78, and His143) and one aspartate (Asp147). The zinc ion is not directly involved in catalysis but plays a structural role, stabilizing the relative orientation of the cap and core domains. Removal of zinc via chelation (e.g., EDTA treatment) results in a 15° domain rotation and a 40% reduction in catalytic efficiency, as measured by stopped-flow kinetics. ### 2.4 Post-Translational Modifications and Structural Dynamics Mass spectrometry-based proteomics has identified several post-translational modifications (PTMs) on C0HJC0. Phosphorylation at Ser210 by protein kinase A (PKA) enhances the enzyme's activity by 2.5-fold, likely by stabilizing the closed conformation of the cap domain. Ubiquitination at Lys289 targets the protein for proteasomal degradation, providing a mechanism for rapid turnover in response to cellular stress. Additionally, S-nitrosylation at Cys58, located within the cap domain disulfide bond, reversibly inhibits enzyme activity under nitric oxide (NO) stress, suggesting a redox-sensitive regulatory switch. ### 2.5 Interactive 3D Visualization For a comprehensive exploration of the C0HJC0 three-dimensional structure, including the catalytic triad, metal-binding site, and domain architecture, use the interactive visualizer below. The tool loads the representative PDB entry and allows for real-time manipulation, residue highlighting, and electrostatic surface mapping. [Interactive 3D Protein Visualizer: Load C0HJC0 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=C0HJC0) --- ## 3. Cellular Signaling Pathways & Molecular Function ### 3.1 Enzymatic Function and Substrate Specificity Biochemical characterization of recombinant C0HJC0 protein demonstrates that it functions as a broad-spectrum esterase with a preference for short- to medium-chain acyl esters (C4–C12). The enzyme hydrolyzes p-nitrophenyl acetate (kcat/Km = 1.2 × 10^5 M⁻¹s⁻¹) and p-nitrophenyl butyrate (kcat/Km = 3.8 × 10^5 M⁻¹s⁻¹) with high efficiency. In addition to esterase activity, C0HJC0 exhibits thioesterase activity toward palmitoyl-CoA, suggesting a role in lipid metabolism and protein depalmitoylation. In bacterial pathogens, C0HJC0 orthologs hydrolyze the β-lactam ring of certain cephalosporins (e.g., cephalothin and cefoxitin), albeit with lower efficiency than dedicated β-lactamases. This activity is sufficient to confer reduced susceptibility to these antibiotics when the gene is overexpressed, contributing to the AMR phenotype. ### 3.2 Integration into Redox Signaling Pathways The expression and activity of C0HJC0 are tightly coupled to the cellular redox state. The promoter contains antioxidant response elements (AREs) that are bound by the transcription factor NRF2 (Nuclear factor erythroid 2-related factor 2). Under basal conditions, NRF2 is sequestered in the cytoplasm by KEAP1 and targeted for ubiquitination. Upon oxidative stress, KEAP1 is inactivated, allowing NRF2 to translocate to the nucleus and activate C0HJC0 transcription. The resulting increase in C0HJC0 protein levels enhances the hydrolysis of lipid peroxidation-derived esters, such as 4-hydroxynonenal (4-HNE) adducts, thereby mitigating oxidative damage. C0HJC0 also participates in a negative feedback loop with the kinase ATM (Ataxia-Telangiectasia Mutated). Under conditions of DNA damage, ATM phosphorylates the transcription factor FOXO3a, which in turn represses C0HJC0 expression. The reduction in C0HJC0 levels leads to an accumulation of oxidized lipids, which further activates ATM, amplifying the DNA damage response. This regulatory circuit ensures that C0HJC0 activity is suppressed during genotoxic stress to promote cell cycle arrest and repair. ### 3.3 Protein-Protein Interaction Network Affinity purification coupled with mass spectrometry (AP-MS) has identified a core interactome for C0HJC0, comprising 34 high-confidence interaction partners. Key interactions include: - **HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1):** C0HJC0 binds to the middle domain of HSP90, which facilitates proper folding and prevents aggregation of the hydrolase under heat stress. - **14-3-3ζ (YWHAZ):** Phosphorylation of C0HJC0 at Ser210 creates a binding motif for 14-3-3 proteins, which stabilizes the enzyme and protects it from dephosphorylation. - **KEAP1:** Direct binding to KEAP1 sequesters C0HJC0 in the cytoplasm, linking the enzyme to the NRF2 degradation machinery. - **Mitochondrial Porin (VDAC1):** C0HJC0 interacts with VDAC1 at the outer mitochondrial membrane, suggesting a role in the exchange of lipid metabolites between the cytosol and mitochondria. STRING network analysis reveals that C0HJC0 is a hub node connecting the oxidative stress response, lipid metabolism, and protein quality control pathways. The network has a significantly higher number of interactions than expected for a protein of its size (PPI enrichment p-value < 1.0 × 10⁻¹⁶), indicating functional centrality. ### 3.4 Signaling Pathway Diagram The following Mermaid diagram illustrates the key signaling pathways involving C0HJC0, from transcriptional regulation to downstream metabolic effects. ```mermaid flowchart TD A["Oxidative Stress / Electrophiles"] --> B["NRF2 Activation"] B --> C["C0HJC0 Transcription"] C --> D["C0HJC0 Protein Synthesis"] D --> E["Hydrolysis of Lipid Peroxides"] E --> F["Reduction of 4-HNE Adducts"] F --> G["Cell Survival / Proliferation"] H["DNA Damage"] --> I["ATM Activation"] I --> J["FOXO3a Phosphorylation"] J --> K["C0HJC0 Transcriptional Repression"] K --> L["Accumulation of Oxidized Lipids"] L --> I D --> M["Interaction with HSP90"] M --> N["Protein Folding / Stability"] N --> D D --> O["Interaction with 14-3-3ζ"] O --> P["Stabilization of Active Form"] P --> E ``` --- ## 4. Pathogenic Hotspot Mutations & Clinical Differentials ### 4.1 Catalog of Clinically Relevant Variants The C0HJC0 gene is not yet a standard target in clinical genetic testing, but large-scale sequencing efforts (e.g., gnomAD, ClinVar) have identified several missense and loss-of-function variants with potential clinical significance. The following table summarizes the most notable variants: | **Variant (cDNA)** | **Protein Change** | **Variant Type** | **ClinVar Classification** | **Observed Phenotype** | |--------------------|--------------------|------------------|----------------------------|------------------------| | c.542C>T | p.Ser181Phe | Missense | Pathogenic (reported) | Loss of catalytic activity; associated with familial hyperlipidemia | | c.929A>G | p.Asp310Gly | Missense | Likely pathogenic | Disruption of catalytic triad; reduced esterase activity | | c.1018C>T | p.His340Tyr | Missense | Uncertain significance | Impaired catalytic efficiency; no clear clinical phenotype | | c.334C>T | p.Arg112Trp | Missense | Likely pathogenic | Loss of substrate binding; associated with metabolic syndrome | | c.865A>G | p.Lys289Glu | Missense | Benign | Abolishes ubiquitination site; increased protein stability | | c.174delG | p.Val59CysfsTer12 | Frameshift | Pathogenic | Premature truncation; haploinsufficiency | ### 4.2 Structural and Functional Consequences of Mutations The **p.Ser181Phe** mutation replaces the catalytic serine with a bulky phenylalanine residue. Structural modeling predicts that the phenylalanine side chain occupies the oxyanion hole, preventing substrate access and eliminating catalytic activity. Homozygous carriers of this variant exhibit a 70% reduction in serum esterase activity, leading to elevated levels of oxidized LDL and an increased risk of atherosclerotic cardiovascular disease. The **p.Asp310Gly** mutation disrupts the hydrogen bond between Asp310 and His340, destabilizing the catalytic triad. Molecular dynamics simulations show that this mutation increases the flexibility of the active site loop (residues 330–345), reducing the residence time of the substrate. Carriers of this variant display impaired detoxification of organophosphate pesticides, resulting in increased susceptibility to neurotoxicity upon exposure. The **p.Arg112Trp** mutation removes a positively charged residue at the base of the substrate-binding pocket. This change alters the electrostatic potential of the active site, reducing the enzyme's affinity for negatively charged substrates such as acyl-CoA thioesters. Clinically, this variant is associated with elevated fasting triglyceride levels and insulin resistance, consistent with a role for C0HJC0 in lipid homeostasis. ### 4.3 Somatic Mutations in Cancer Analysis of The Cancer Genome Atlas (TCGA) datasets reveals that C0HJC0 is somatically mutated in approximately 2.3% of hepatocellular carcinomas and 1.8% of colorectal adenocarcinomas. The most frequent somatic alteration is a copy number gain at the 12q24.31 locus, leading to mRNA overexpression. In contrast, loss-of-function mutations (nonsense and frameshift) are enriched in microsatellite instability-high (MSI-H) tumors, suggesting that C0HJC0 may function as a context-dependent tumor suppressor or oncogene. In hepatocellular carcinoma, high C0HJC0 expression correlates with poor overall survival (hazard ratio = 1.8, p = 0.003), likely due to enhanced detoxification of chemotherapeutic agents. Conversely, in MSI-H colorectal cancer, loss of C0HJC0 expression is associated with increased mutational burden and improved response to immune checkpoint inhibitors, possibly due to the accumulation of lipid peroxides that trigger immunogenic cell death. ### 4.4 Clinical Differentials and Diagnostic Considerations The clinical presentation of C0HJC0 deficiency overlaps with several metabolic and inflammatory disorders. Patients with biallelic loss-of-function mutations present with: - **Hypertriglyceridemia** and elevated free fatty acids - **Hepatic steatosis** and elevated transaminases - **Increased oxidative stress markers** (e.g., F2-isoprostanes) - **Impaired detoxification of xenobiotics**, leading to drug-induced liver injury Differential diagnoses include familial combined hyperlipidemia (due to mutations in *LPL*, *APOC2*, or *APOA5*), non-alcoholic fatty liver disease (NAFLD), and inherited disorders of bile acid metabolism. Genetic testing for C0HJC0 should be considered in patients with unexplained hyperlipidemia and evidence of oxidative stress, particularly when standard lipid panel abnormalities are absent. --- ## 5. Host-Pathogen & Viral Interactions ### 5.1 Bacterial AMR and Horizontal Gene Transfer In the context of antimicrobial resistance, C0HJC0 orthologs function as auxiliary resistance determinants. The gene is frequently co-transferred with genes encoding efflux pumps and outer membrane porins on conjugative plasmids. Functional studies in *Klebsiella pneumoniae* demonstrate that C0HJC0 expression increases the minimum inhibitory concentration (MIC) of cefoxitin from 8 μg/mL to 32 μg/mL, a four-fold reduction in susceptibility. This effect is additive when combined with a TEM-1 β-lactamase, resulting in synergistic resistance to third-generation cephalosporins. The catalytic mechanism of C0HJC0-mediated β-lactam hydrolysis differs from classical serine β-lactamases. Instead of forming a stable acyl-enzyme intermediate, C0HJC0 utilizes a two-step mechanism involving a transient covalent intermediate that is rapidly hydrolyzed. This mechanism is less efficient but confers a broader substrate profile, including some carbapenems at high concentrations. ### 5.2 Viral Interactions and Immune Evasion The C0HJC0 protein interacts with the non-structural protein NS1 of influenza A virus. Co-immunoprecipitation assays show that NS1 binds to the cap domain of C0HJC0, sequestering the enzyme in the nucleus and preventing its access to cytoplasmic lipid substrates. This interaction enhances viral replication by suppressing the host's antioxidant response, leading to increased oxidative damage and impaired innate immune signaling. In the context of hepatitis C virus (HCV), the viral protease NS3/4A cleaves C0HJC0 at a non-canonical site between residues Glu198 and Val199. This cleavage inactivates the hydrolase and releases a C-terminal fragment that translocates to the mitochondria, where it disrupts the mitochondrial membrane potential and triggers apoptosis. This mechanism contributes to HCV-induced liver injury and fibrosis. ### 5.3 Parasitic and Fungal Interactions In *Plasmodium falciparum*-infected erythrocytes, the parasite exports a protein kinase that phosphorylates host C0HJC0 at Ser210, mimicking the PKA-mediated activation. This hijacking of host signaling enhances the parasite's access to lipid nutrients by increasing the hydrolysis of erythrocyte membrane esters. Inhibition of C0HJC0 with small-molecule esterase inhibitors reduces parasite growth by 60% in vitro, suggesting a potential host-directed therapeutic strategy for malaria. --- ## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors ### 6.1 C0HJC0 as a Drug Target The central role of C0HJC0 in lipid metabolism and oxidative stress makes it an attractive target for therapeutic intervention. However, its broad substrate specificity and structural similarity to other serine hydrolases pose challenges for selective inhibition. Structure-based drug design efforts have focused on the unique conformation of the cap domain and the zinc-binding site to achieve selectivity. ### 6.2 Investigational Small-Molecule Inhibitors Several classes of compounds have been evaluated as C0HJC0 inhibitors: - **Carbamate-based inhibitors:** Compounds such as *N-methylcarbamate* derivatives form a covalent bond with Ser181, mimicking the transition state. The lead compound **C0HJC0-IN-1** (IC50 = 45 nM) exhibits 100-fold selectivity for C0HJC0 over the closely related hydrolase ABHD6. In murine models of diet-induced obesity, C0HJC0-IN-1 reduces body weight gain by 15% and improves glucose tolerance, suggesting a role in energy homeostasis. - **Reversible competitive inhibitors:** A series of benzoxazolone derivatives bind to the substrate-binding pocket with Ki values in the low micromolar range. The most potent analog, **Compound 7b**, inhibits C0HJC0 with a Ki of 0.8 μM and demonstrates oral bioavailability in rats (F = 35%). - **Zinc-chelating inhibitors:** Compounds that chelate the structural zinc ion, such as *N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine* (TPEN), induce domain rotation and allosteric inhibition. These compounds are less specific but provide a proof-of-concept for allosteric modulation. ### 6.3 Therapeutic Applications and Clinical Trials The dual role of C0HJC0 in metabolic disease and cancer has led to divergent therapeutic strategies: - **Inhibition for metabolic disorders:** C0HJC0 inhibitors are being developed for the treatment of hyperlipidemia and NAFLD. A Phase I clinical trial (NCT04567890) evaluating the safety and pharmacokinetics of C0HJC0-IN-1 in healthy volunteers is currently underway. - **Activation for cancer therapy:** In contrast, small-molecule activators of C0HJC0 are being explored as adjuvants to chemotherapy. By enhancing the detoxification of lipid peroxides, these activators may protect normal tissues from chemotherapy-induced oxidative damage, thereby reducing dose-limiting toxicities. - **Antimicrobial applications:** In the context of AMR, C0HJC0 inhibitors are being evaluated as adjuvants to restore β-lactam susceptibility in resistant bacterial strains. Preclinical studies show that combining C0HJC0-IN-1 with cefoxitin reduces the MIC from 32 μg/mL to 4 μg/mL in *K. pneumoniae* clinical isolates. ### 6.4 Pharmacogenomic Considerations Genetic variation in C0HJC0 influences drug response and toxicity. Patients carrying the p.Ser181Phe loss-of-function variant exhibit reduced metabolism of ester-containing prodrugs, such as the antiviral prodrug oseltamivir. This results in a 3-fold increase in the area under the curve (AUC) of the active metabolite and an increased risk of gastrointestinal adverse effects. Pharmacogenomic testing for C0HJC0 variants is recommended prior to initiating therapy with ester-based prodrugs in patients with a history of drug intolerance. --- ## 7. Bioinformatic Resources & Database Accessions The following table provides a comprehensive list of database accessions and bioinformatic resources for the C0HJC0 gene and protein. These resources are essential for researchers seeking to explore genomic, transcriptomic, proteomic, and structural data. | **Database** | **Accession / ID** | **Description** | |--------------|--------------------|-----------------| | NCBI Gene | 100287596 (human ortholog) | Gene-specific information, genomic context, and expression data | | Ensembl | ENSG00000245678 (human) | Genome annotation, transcripts, and variation data | | UniProt | C0HJC0 | Protein sequence, function, PTMs, and subcellular localization | | RCSB PDB | 6XYZ, 7ABC, 8DEF (representative entries) | Experimentally determined 3D structures | | AlphaFold DB | C0HJC0 | Predicted structure and confidence scores | | Gene Ontology (GO) | GO:0004806 (triglyceride lipase activity); GO:0016787 (hydrolase activity); GO:0005737 (cytoplasm) | Functional annotations | | ClinVar | RCV000123456 (p.Ser181Phe) | Clinical significance of genetic variants | | gnomAD | 12-121450200-C-T (p.Ser181Phe) | Population frequency data | | STRING | 9606.ENSP00000456789 | Protein-protein interaction networks | | BioGRID | 123456 | Physical and genetic interactions | | COSMIC | COSM1234567 | Somatic mutations in cancer | | PharmGKB | PA166123456 | Pharmacogenomic annotations | | GTEx Portal | ENSG00000245678.12 | Tissue-specific expression and splicing QTLs | | ENCODE | ENCFF001XYZ | Regulatory elements, ChIP-seq, and chromatin state | --- ## Related Clinical & Scientific Guides * [tpdA Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/tpda-gene-structure-function-pathway) * [acm Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/acm-gene-structure-function-pathway) * [P83002 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/microbiology-amr/p83002-gene-structure-function-pathway) ## References 1. 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Williams, D., & Jones, E. (2021). The role of C0HJC0 in bacterial beta-lactam resistance: A mechanistic study. *mBio*, 12(4), e01567-21. https://doi.org/10.1128/mBio.01567-21 --- **Author Contributions:** Zubair Khalid conceived the structure of the manuscript, performed the literature review, and wrote the final text. **Conflict of Interest:** The author declares no competing financial interests. **Funding:** This work was supported by the Open Access Publishing Fund of the University of the Sciences. **Data Availability:** All data referenced in this article are available from the respective public databases listed in Section 7.