Details for: AK7

Gene ID: 122481

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: AK7

Ensembl ID: ENSG00000140057

Description: adenylate kinase 7

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • ciliated epithelial cell CL0000067
    CSI 5.81
    rCSI 5.11%
    PRS 96.67
  • lung ciliated cell CL1000271
    CSI 5.56
    rCSI 6.43%
    PRS 97.53
  • choroid plexus epithelial cell CL0000706
    CSI 4.34
    rCSI 7.1%
    PRS 97.52
  • squamous epithelial cell CL0000076
    CSI 4.32
    rCSI 10.26%
    PRS 96.81
  • glioblast CL0000030
    CSI 4.11
    rCSI 6.56%
    PRS 96.92
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.59
    rCSI 4.46%
    PRS 95.77
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 3.5
    rCSI 4.96%
    PRS 98.48
  • multi-ciliated epithelial cell CL0005012
    CSI 3.39
    rCSI 3.39%
    PRS 97.39
  • ciliated cell CL0000064
    CSI 2.74
    rCSI 4.44%
    PRS 96.77
  • ependymal cell CL0000065
    CSI 2.61
    rCSI 5.29%
    PRS 93.57
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.39
    rCSI 6.17%
    PRS 98.59
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.32
    rCSI 3.01%
    PRS 96.45
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.31
    rCSI 4.95%
    PRS 95.76
  • deuterosomal cell CL4033044
    CSI 1.19
    rCSI 4.02%
    PRS 96.28

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.

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  • 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)

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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 [AK7](/details-gene/122481) encodes adenylate kinase 7, a member of the adenylate kinase family responsible for catalyzing the interconversion of adenine nucleotides (AMP, ADP, ATP). This enzymatic activity is fundamental to cellular energy homeostasis and nucleotide metabolism. **Overall**, expression data reveals that [AK7](/details-gene/122481) is a highly significant gene in cells possessing motile cilia, with its highest significance observed in `ciliated epithelial cell`s ([CL0000067](/details-cell/CL0000067)), `lung ciliated cell`s ([CL1000271](/details-cell/CL1000271)), and `choroid plexus epithelial cell`s ([CL0000706](/details-cell/CL0000706)). Clinically, its function is critically linked to the motility of specialized cilia; homozygous mutations in [AK7](/details-gene/122481) have been shown to cause primary male infertility due to multiple morphological anomalies of the sperm flagella ([Link](https://doi.org/10.1093/hmg/ddy034)). ## Cellular Roles and Expression Landscape The expression profile of [AK7](/details-gene/122481) strongly suggests a specialized role in maintaining the function of motile cilia. The gene shows its highest significance scores in a variety of ciliated cell types across different tissues. These include `ciliated epithelial cell`s (CSI: 5.81) of the respiratory tract, such as `lung ciliated cell`s (CSI: 5.56) and `ciliated columnar cell of tracheobronchial tree` ([CL0002145](/details-cell/CL0002145)) (CSI: 1.32), as well as ciliated cells of the central nervous system like `choroid plexus epithelial cell`s (CSI: 4.34) and `ependymal cell`s ([CL0000065](/details-cell/CL0000065)) (CSI: 2.61). This pattern indicates a conserved function in powering ciliary movement in diverse anatomical locations. Interestingly, despite its high expression in respiratory ciliated cells, known pathogenic mutations specifically lead to defects in sperm flagella—a modified motile cilium—without causing the broader symptoms of primary ciliary dyskinesia ([Link](https://doi.org/10.1093/hmg/ddy034)). This suggests that the function of [AK7](/details-gene/122481) may be uniquely critical in spermatogenesis, whereas its role in other ciliated cells might be compensated for by other adenylate kinase isoenzymes. The gene also shows notable significance in `glioblast` ([CL0000030](/details-cell/CL0000030)) (CSI: 4.11), suggesting a potential, albeit less characterized, role in the metabolic activity of this brain tumor cell type. ## Pathways and Molecular Function [AK7](/details-gene/122481)'s primary molecular function is adenylate kinase activity ([GO:0004017](https://www.ebi.ac.uk/QuickGO/term/GO:0004017)), which involves the reversible reaction ATP + AMP <=> 2 ADP. This function is a key component of broader metabolic pathways, including the '[Interconversion of nucleotide di- and triphosphates](https://reactome.org/content/detail/R-HSA-499943)' ([R-HSA-499943](https://reactome.org/content/detail/R-HSA-499943)) and '[Metabolism of nucleotides](https://reactome.org/content/detail/R-HSA-15869)' ([R-HSA-15869](https://reactome.org/content/detail/R-HSA-15869)). The enzyme's distinct kinetic parameters have been previously characterized ([Link](https://doi.org/10.1042/bj20101443)). Functionally, this enzymatic activity is tightly linked to its subcellular localization within the `motile cilium` ([GO:0031514](https://www.ebi.ac.uk/QuickGO/term/GO:0031514)) and its involvement in `cell projection organization` ([GO:0030030](https://www.ebi.ac.uk/QuickGO/term/GO:0030030)). The constant movement of cilia and flagella is an energy-intensive process driven by dynein ATPases. [AK7](/details-gene/122481) is thought to play a crucial role in locally regenerating ATP from ADP within the ciliary compartment, thereby providing the fuel necessary to sustain motility. This localized energy supply system is critical for the proper function of these organelles, and its disruption explains the flagellar defects observed in patients with [AK7](/details-gene/122481) mutations. ## Research Directions The specific link between [AK7](/details-gene/122481) mutations and male infertility, but not classical primary ciliary dyskinesia (PCD), presents a key area for future investigation. This discrepancy suggests cell-type-specific dependencies on [AK7](/details-gene/122481) for ciliary function. **Proposed Hypotheses:** 1. The function of [AK7](/details-gene/122481) in respiratory `ciliated epithelial cell`s ([CL0000067](/details-cell/CL0000067)) is functionally redundant, with other adenylate kinase isoforms (e.g., AK1, AK2) compensating for its loss. The unique metabolic and structural environment of the sperm flagellum, however, renders it critically dependent solely on [AK7](/details-gene/122481) for maintaining the necessary ATP supply for motility. 2. The high significance of [AK7](/details-gene/122481) in `glioblast`s ([CL0000030](/details-cell/CL0000030)) reflects a role in supporting the high energetic and proliferative demands of these cancer cells. In this context, its function would be related to general cellular metabolism rather than ciliary motility. **Experimental Approach:** To test the functional redundancy hypothesis (Hypothesis 1), one could utilize an *in vitro* model of the human airway epithelium. Specifically, CRISPR-Cas9 could be used to generate an [AK7](/details-gene/122481) knockout in primary human bronchial epithelial cells. These cells would then be cultured at an air-liquid interface to promote differentiation into a mature, ciliated epithelium. High-speed video microscopy could then be used to precisely measure ciliary beat frequency and waveform in the [AK7](/details-gene/122481)-deficient cells compared to wild-type controls. The hypothesis predicts that the knockout would result in little to no significant change in ciliary function, which would support the theory of redundancy in these cells. **Therapeutic Potential:** As a cause of monogenic male infertility, [AK7](/details-gene/122481) is primarily a diagnostic target. However, its significant expression in `glioblast`s ([CL0000030](/details-cell/CL0000030)) could present a therapeutic opportunity. If this highly metabolic cancer is dependent on [AK7](/details-gene/122481) for nucleotide homeostasis, then selective **inhibition** of its enzymatic activity could be a strategy to slow tumor growth. Given that the protein is located in the cytoplasm, a cell-permeable small molecule inhibitor would be the required therapeutic modality. The viability of this approach would depend on the degree of tumor dependency on [AK7](/details-gene/122481) versus healthy tissues.

Genular Protein ID: 1684407382

Symbol: KAD7_HUMAN

Name: Adenylate kinase 7

UniProtKB Accession Codes:

Q96M32 Q8IYP6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 17 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 3 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 8 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 3 SABIO-RK 1 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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

PubMed ID: 21080915

Title: The characterization of human adenylate kinases 7 and 8 demonstrates differences in kinetic parameters and structural organization among the family of adenylate kinase isoenzymes.

PubMed ID: 21080915

DOI: 10.1042/bj20101443

PubMed ID: 23416111

Title: The human adenylate kinase 9 is a nucleoside mono- and diphosphate kinase.

PubMed ID: 23416111

DOI: 10.1016/j.biocel.2013.02.004

PubMed ID: 29365104

Title: Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia.

PubMed ID: 29365104

DOI: 10.1093/hmg/ddy034

Sequence Information:

  • Length: 723
  • Mass: 82658
  • Checksum: 7A9E2BF11A4CEEF8
  • Sequence:
    • MAEEEETAAL TEKVIRTQRV FINLLDSYSS GNIGKFLSNC VVGASLEEIT EEEEEEDENK 
SAMLEASSTK VKEGTFQIVG TLSKPDSPRP DFAVETYSAI SREDLLMRLL ECDVIIYNIT 
ESSQQMEEAI WAVSALSEEV SHFEKRKLFI LLSTVMTWAR SKALDPEDSE VPFTEEDYRR 
RKSHPNFLDH INAEKMVLKF GKKARKFAAY VVAAGLQYGA EGGMLHTFFK MAWLGEIPAL 
PVFGDGTNVI PTIHVLDLAG VIQNVIDHVP KPHYLVAVDE SVHTLEDIVK CISKNTGPGK 
IQKIPRENAY LTKDLTQDCL DHLLVNLRME ALFVKENFNI RWAAQTGFVE NINTILKEYK 
QSRGLMPIKI CILGPPAVGK SSIAKELANY YKLHHIQLKD VISEAIAKLE AIVAPNDVGE 
GEEEVEEEEE EENVEDAQEL LDGIKESMEQ NAGQLDDQYI IRFMKEKLKS MPCRNQGYIL 
DGFPKTYDQA KDLFNQEDEE EEDDVRGRMF PFDKLIIPEF VCALDASDEF LKERVINLPE 
SIVAGTHYSQ DRFLRALSNY RDINIDDETV FNYFDELEIH PIHIDVGKLE DAQNRLAIKQ 
LIKEIGEPRN YGLTDEEKAE EERKAAEERL AREAAEEAER EHQEAVEMAE KIARWEEWNK 
RLEEVKREER ELLEAQSIPL RNYLMTYVMP TLIQGLNECC NVRPEDPVDF LAEYLFKNNP 
EAQ