Details for: SPAG17

Gene ID: 200162

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: SPAG17

Ensembl ID: ENSG00000155761

Description: sperm associated antigen 17

Cell Significance Landscape

Associated with

Significant Cells

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

  • ependymal cell CL0000065
    CSI 26.44
    rCSI 53.64%
    PRS 97.13
  • ciliated epithelial cell CL0000067
    CSI 23.68
    rCSI 20.83%
    PRS 98.81
  • lung ciliated cell CL1000271
    CSI 19.27
    rCSI 22.29%
    PRS 99.2
  • multi-ciliated epithelial cell CL0005012
    CSI 17.38
    rCSI 17.34%
    PRS 99.14
  • ciliated cell CL0000064
    CSI 14.08
    rCSI 22.8%
    PRS 98.75
  • choroid plexus epithelial cell CL0000706
    CSI 12.62
    rCSI 20.66%
    PRS 99.02
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 8.99
    rCSI 20.49%
    PRS 98.77
  • glioblast CL0000030
    CSI 7.05
    rCSI 11.25%
    PRS 99.06
  • neural progenitor cell CL0011020
    CSI 6
    rCSI 26.41%
    PRS 96.97
  • epithelial cell of proximal tubule CL0002306
    CSI 5.95
    rCSI 14.53%
    PRS 98.66
  • GABAergic neuron CL0000617
    CSI 5.67
    rCSI 18.98%
    PRS 97.27
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 5.38
    rCSI 7.62%
    PRS 99.52
  • kidney connecting tubule epithelial cell CL1000768
    CSI 5.18
    rCSI 13.13%
    PRS 99.33
  • retinal cone cell CL0000573
    CSI 5.12
    rCSI 8.25%
    PRS 98.56
  • retinal ganglion cell CL0000740
    CSI 4.62
    rCSI 10.21%
    PRS 98.74
  • parietal epithelial cell CL1000452
    CSI 4.1
    rCSI 10.95%
    PRS 99.39
  • renal principal cell CL0005009
    CSI 3.97
    rCSI 10.32%
    PRS 99.83
  • chondrocyte CL0000138
    CSI 3.92
    rCSI 6.23%
    PRS 98.87
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.89
    rCSI 4.65%
    PRS 98.75
  • deuterosomal cell CL4033044
    CSI 3.68
    rCSI 12.44%
    PRS 98.74
  • squamous epithelial cell CL0000076
    CSI 3.64
    rCSI 8.64%
    PRS 98.64
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 3.25
    rCSI 8.39%
    PRS 99.59
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.72
    rCSI 6.19%
    PRS 98.48
  • direct pathway medium spiny neuron CL4023026
    CSI 0.75
    rCSI 17.84%
    PRS 97.77
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.59
    rCSI 6.22%
    PRS 99.29
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.58
    rCSI 13.96%
    PRS 97.75

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)

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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 [SPAG17](/details-gene/200162) (Sperm Associated Antigen 17) is a protein-coding gene located on chromosome 1p12. Functionally, it is integral to the assembly and movement of motile cilia and flagella. Its primary role involves the formation of the axonemal central apparatus, a core microtubular structure essential for ciliary and flagellar motility. This function is reflected in its highly specific and abundant expression in ciliated cell types, including [ependymal cell](/details-cell/CL0000065)s in the brain and various [ciliated epithelial cell](/details-cell/CL0000067)s throughout the body. Clinically, mutations in [SPAG17](/details-gene/200162) have been associated with male infertility due to impaired sperm motility ([Link](https://doi.org/10.1111/cge.13059)). ## Cellular Roles and Expression Landscape The expression profile of [SPAG17](/details-gene/200162) strongly underscores its role as a key structural component of motile cilia. **Overall**, the gene shows the highest significance in cell types characterized by the presence of these organelles. The top-ranking cells are functionally related and include [ependymal cell](/details-cell/CL0000065) (CSI: 26.44), which lines the ventricles of the brain and facilitates cerebrospinal fluid circulation, and multiple types of ciliated epithelial cells such as [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 23.68), [lung ciliated cell](/details-cell/CL1000271) (CSI: 19.27), and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145) (CSI: 8.99). This pattern highlights a conserved and critical role for [SPAG17](/details-gene/200162) in mucus and fluid movement in both the central nervous system and the respiratory tract. High significance in [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 12.62) is also consistent with this theme. Interestingly, [SPAG17](/details-gene/200162) also shows significant expression in cell types where motile cilia are less prominent or have specialized functions, such as [glioblast](/details-cell/CL0000030) (CSI: 7.05) and [neural progenitor cell](/details-cell/CL0011020) (CSI: 6.00). This may suggest a potential role in primary cilia, which are involved in cell signaling, or it could reflect specific developmental processes. The gene's specific expression pattern in these specialized cells, and its notable absence in major hematopoietic and mesenchymal lineages, suggests it is a highly specific marker for ciliated cells and their precursors. ## Pathways and Molecular Function The functional annotations for [SPAG17](/details-gene/200162) align precisely with its observed cellular expression pattern. It is heavily involved in biological processes related to the formation and function of microtubule-based cellular projections. Key Gene Ontology (GO) terms include '[Motile cilium assembly](/details-go/GO:0044458)', '[Axonemal central apparatus assembly](/details-go/GO:1904158)', and '[Epithelial cilium movement involved in extracellular fluid movement](/details-go/GO:0003351)'. These functions are essential for the roles of [ependymal cell](/details-cell/CL0000065)s and respiratory ciliated cells where the gene is most prominent. Its specific involvement in the male reproductive system is annotated by processes such as '[Spermatogenesis](/details-go/GO:0007283)' and cellular components like the '[Manchette](/details-go/GO:0002177)' and '[Acrosomal vesicle](/details-go/GO:0001669)'. The manchette is a transient microtubular structure crucial for shaping the sperm head during spermatogenesis. This is consistent with research identifying a homozygous mutation in [SPAG17](/details-gene/200162) as a cause of severe asthenozoospermia (impaired sperm motility) in a familial study ([Link](https://doi.org/10.1111/cge.13059)). Furthermore, research has shown that the protein interacts with SPAG6, the mammalian orthologue of Chlamydomonas PF16, another central apparatus protein, reinforcing its structural role within the axoneme ([Link](https://doi.org/10.1074/mcp.m400177-mcp200)). ## Research Directions The specific expression and critical function of [SPAG17](/details-gene/200162) in ciliary structures present several avenues for future investigation, particularly concerning ciliopathies and cancer biology. ### Proposed Hypotheses: 1. **Hypothesis 1:** Given its fundamental role in axoneme assembly, heterozygous loss-of-function mutations in [SPAG17](/details-gene/200162) may contribute to the spectrum of primary ciliary dyskinesia (PCD), a genetically heterogeneous disorder affecting motile cilia. While homozygous mutations are linked to infertility, heterozygous carriers may exhibit subclinical respiratory or neurological symptoms that have not yet been systematically investigated. 2. **Hypothesis 2:** The unexpected high expression of [SPAG17](/details-gene/200162) in [glioblast](/details-cell/CL0000030) suggests a co-opted or alternative function in tumorigenesis. [SPAG17](/details-gene/200162) may regulate glioblastoma cell migration or proliferation through its involvement in the primary cilium, a known hub for developmental and oncogenic signaling pathways like Sonic Hedgehog (Shh) and Wnt. ### Key Experiment: To test Hypothesis 2, one could investigate the function of [SPAG17](/details-gene/200162) in glioblastoma cell biology. A proposed experiment would involve: * **Method:** Use CRISPR-Cas9 to generate stable [SPAG17](/details-gene/200162) knockout and control (non-targeting gRNA) glioblastoma cell lines (e.g., U-87 MG). * **Assays:** * **Ciliary Analysis:** Use immunofluorescence microscopy to stain for primary cilia markers (e.g., Arl13b, acetylated alpha-tubulin) to determine if [SPAG17](/details-gene/200162) loss affects cilia formation or length. * **Signaling Pathway Analysis:** Employ qPCR and Western blotting to measure the expression of downstream targets of the Shh pathway (e.g., *GLI1*, *PTCH1*) with and without pathway stimulation by an agonist like SAG. * **Functional Assays:** Perform in vitro scratch assays (wound healing) and Transwell migration assays to assess whether knockout of [SPAG17](/details-gene/200162) alters the migratory and invasive capacity of glioblastoma cells. ### Therapeutic Potential: As a therapeutic target, [SPAG17](/details-gene/200162) presents a challenging profile. Its fundamental role in the function of essential ciliated cells in the brain, respiratory tract, and reproductive system means that systemic inhibition would likely lead to severe, multi-organ toxicity, resembling a systemic ciliopathy. Therefore, it is a poor candidate for inhibitory drugs in contexts like cancer. However, for congenital disorders like male infertility caused by biallelic loss-of-function mutations, [SPAG17](/details-gene/200162) could be a candidate for future gene replacement therapies aimed at restoring protein function in spermatogonial stem cells, although this remains a highly speculative and technically challenging approach.

Genular Protein ID: 3911652729

Symbol: SPG17_HUMAN

Name: Sperm-associated antigen 17

UniProtKB Accession Codes:

Q6Q759 Q8NAZ1 Q9NT21

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 13 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15827353

Title: Dissecting the axoneme interactome: the mammalian orthologue of Chlamydomonas PF6 interacts with sperm-associated antigen 6, the mammalian orthologue of Chlamydomonas PF16.

PubMed ID: 15827353

DOI: 10.1074/mcp.m400177-mcp200

PubMed ID: 16710414

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

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 16959974

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

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 28548327

Title: A familial study of twins with severe asthenozoospermia identified a homozygous SPAG17 mutation by whole-exome sequencing.

PubMed ID: 28548327

DOI: 10.1111/cge.13059

Sequence Information:

  • Length: 2223
  • Mass: 251742
  • Checksum: 07C248C5B2A5B561
  • Sequence:
    • MAPKKEKGGT VNTSSKIWEP SLIAAQFNQN DWQASIAFVV GNQIEDDLLI QALTVAVQVP 
QRKLFSMVSW QDILQQINEI NTLVGSASSK KAKKPVGGNA PLYYEVLTAA KAIMDSGEKL 
TLPLIGKLLK FQLLQIKFKD QQRRENEKKV IEDKPKLEKD KGKAKSPKEK KAPSAKPAKG 
KGKDQPEANA PVKKTTQLKR RGEDDHTNRY IDDEPDDGAQ HYIIVVGFNN PQLLAIMAEL 
GIPITSVIKI SSENYEPLQT HLAAVNQQQE VLLQSEDLEA EKLKKENAIK ELKTFWKYLE 
PVLNNEKPET NLFDVARLEY MVKAADFPSD WSDGEMMLKL GTDIFENIAC LMYDILDWKR 
QHQHYLESMQ LINVPQVVNE KPVLEAMPTS EAPQPAVPAP GKKKAQYEEP QAPPPVTSVI 
TTEVDMRYYN YLLNPIREEF ISVPLILHCM LEQVVATEED LVPPSLREPS PRADGLDHRI 
AAHIVSLLPS LCLSEREKKN LHDIFLSEEE NESKAVPKGP LLLNYHDAHA HKKYALQDQK 
NFDPVQIEQE MQSKLPLWEF LQFPLPPPWN NTKRLATIHE LMHFCTSDVL SWNEVERAFK 
VFTFESLKLS EVDEKGKLKP SGMMCGSDSE MFNIPWDNPA RFAKQIRQQY VMKMNTQEAK 
QKADIKIKDR TLFVDQNLSM SVQDNESNRE PSDPSQCDAN NMKHSDLNNL KLSVPDNRQL 
LEQESIMKAQ PQHESLEQTT NNEIKDDAVT KADSHEKKPK KMMVEADLED IKKTQQRSLM 
DWSFTEHFKP KVLLQVLQEA HKQYRCVDSY YHTQDNSLLL VFHNPMNRQR LHCEYWNIAL 
HSNVGFRNYL ELVAKSIQDW ITKEEAIYQE SKMNEKIIRT RAELELKSSA NAKLTSASKI 
FSIKESKSNK GISKTEISDQ EKEKEKEKIP FILEGSLKAW KEEQHRLAEE ERLREEKKAE 
KKGKEAGKKK GKDNAEKEDS RSLKKKSPYK EKSKEEQVKI QEVTEESPHQ PEPKITYPFH 
GYNMGNIPTQ ISGSNYYLYP SDGGQIEVEK TMFEKGPTFI KVRVVKDNHN FMIHLNDPKE 
IVKKEEKGDY YLEEEEEGDE EQSLETEVSD AKNKAFSKFG SFSATLENGI CLSISYYGSN 
GMAPEDKDPD LETILNIPSA LTPTVVPVIV TVPQSKAKGK IKGKEKPKES LKEEEHPKEE 
EKKEEEVEPE PVLQETLDVP TFQSLNVSCP SGLLLTFIGQ ESTGQYVIDE EPTWDIMVRQ 
SYPQRVKHYE FYKTVMPPAE QEASRVITSQ GTVVKYMLDG STQILFADGA VSRSPNSGLI 
CPPSEMPATP HSGDLMDSIS QQKSETIPSE ITNTKKGKSH KSQSSMAHKG EIHDPPPEAV 
QTVTPVEVHI GTWFTTTPEG NRIGTKGLER IADLTPLLSF QATDPVNGTV MTTREDKVVI 
VERKDGTRIV DHADGTRITT FYQVYEDQII LPDDQETTEG PRTVTRQVKC MRVESSRYAT 
VIANCEDSSC CATFGDGTTI IAKPQGTYQV LPPNTGSLYI DKDCSAVYCH ESSSNIYYPF 
QKREQLRAGR YIMRHTSEVI CEVLDPEGNT FQVMADGSIS TILPEKKLED DLNEKTEGYD 
SLSSMHLEKN HQQIYGEHVP RFFVMYADGS GMELLRDSDI EEYLSLAYKE SNTVVLQEPV 
QEQPGTLTIT VLRPFHEASP WQVKKEDTIV PPNLRSRSWE TFPSVEKKTP GPPFGTQIWK 
GLCIESKQLV SAPGAILKSP SVLQMRQFIQ HEVIKNEVKL RLQVSLKDYI NYILKKEDEL 
QEMMVKDSRT EEERGNAADL LKLVMSFPKM EETTKSHVTE VAAHLTDLFK QSLATPPKCP 
PDTFGKDFFE KTWRHTASSK RWKEKIDKTR KEIETTQNYL MDIKNRIIPP FFKSELNQLY 
QSQYNHLDSL SKKLPSFTKK NEDANETAVQ DTSDLNLDFK PHKVSEQKSS SVPSLPKPEI 
SADKKDFTAQ NQTENLTKSP EEAESYEPVK IPTQSLLQDV AGQTRKEKVK LPHYLLSSKP 
KSQPLAKVQD SVGGKVNTSS VASAAINNAK SSLFGFHLLP SSVKFGVLKE GHTYATVVKL 
KNVGVDFCRF KVKQPPPSTG LKVTYKPGPV AAGMQTELNI ELFATAVGED GAKGSAHISH 
NIEIMTEHEV LFLPVEATVL TSSNYDKRPK DFPQGKENPM VQRTSTIYSS TLGVFMSRKV 
SPH