Details for: SPAG1

Gene ID: 6674

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: SPAG1

Ensembl ID: ENSG00000104450

Description: sperm associated antigen 1

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 30.11
    rCSI 26.47%
    PRS 70.18
  • lung ciliated cell CL1000271
    CSI 27.41
    rCSI 31.69%
    PRS 73.21
  • multi-ciliated epithelial cell CL0005012
    CSI 24.32
    rCSI 24.27%
    PRS 74.74
  • ependymal cell CL0000065
    CSI 22.82
    rCSI 46.31%
    PRS 59.51
  • ciliated cell CL0000064
    CSI 15.86
    rCSI 25.7%
    PRS 75.72
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 11.04
    rCSI 25.16%
    PRS 74.42
  • retinal ganglion cell CL0000740
    CSI 7.4
    rCSI 16.34%
    PRS 66.71
  • deuterosomal cell CL4033044
    CSI 6.04
    rCSI 20.41%
    PRS 78.3
  • choroid plexus epithelial cell CL0000706
    CSI 5.84
    rCSI 9.56%
    PRS 70.43
  • transit amplifying cell CL0009010
    CSI 5.76
    rCSI 8.81%
    PRS 88.6
  • cardiac muscle cell CL0000746
    CSI 4.53
    rCSI 6.5%
    PRS 70.77
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.47
    rCSI 3.47%
    PRS 84.39
  • secretory cell CL0000151
    CSI 4.42
    rCSI 4.61%
    PRS 80.1
  • nasal mucosa goblet cell CL0002480
    CSI 4
    rCSI 4.64%
    PRS 84.41
  • regular atrial cardiac myocyte CL0002129
    CSI 3.84
    rCSI 12.35%
    PRS 77.53
  • cerebral cortex endothelial cell CL1001602
    CSI 3.72
    rCSI 6.44%
    PRS 72.52
  • stem cell CL0000034
    CSI 3.49
    rCSI 3.36%
    PRS 74.23
  • mucus secreting cell CL0000319
    CSI 3.49
    rCSI 5.54%
    PRS 88.87
  • inhibitory interneuron CL0000498
    CSI 3.3
    rCSI 7.63%
    PRS 68.87
  • sncg GABAergic cortical interneuron CL4023015
    CSI 3.24
    rCSI 5.21%
    PRS 64.57
  • precursor B cell CL0000817
    CSI 3.09
    rCSI 2.7%
    PRS 87.57
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 3.08
    rCSI 3.83%
    PRS 60.93
  • brush cell of tracheobronchial tree CL0002075
    CSI 3.05
    rCSI 9.06%
    PRS 88.82
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.89
    rCSI 4.09%
    PRS 77.52
  • pancreatic A cell CL0000171
    CSI 2.87
    rCSI 3.01%
    PRS 83.88
  • glioblast CL0000030
    CSI 2.85
    rCSI 4.55%
    PRS 72.44
  • cerebellar granule cell CL0001031
    CSI 2.76
    rCSI 4.06%
    PRS 73.89
  • pancreatic D cell CL0000173
    CSI 2.72
    rCSI 2.68%
    PRS 83.29
  • epithelial cell of lung CL0000082
    CSI 2.69
    rCSI 2.23%
    PRS 81.47
  • lung neuroendocrine cell CL1000223
    CSI 2.65
    rCSI 3.92%
    PRS 84.54
  • group 3 innate lymphoid cell CL0001071
    CSI 2.62
    rCSI 1.97%
    PRS 86.09
  • interneuron CL0000099
    CSI 2.59
    rCSI 5.2%
    PRS 71.23
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.56
    rCSI 3.06%
    PRS 63.15
  • neural progenitor cell CL0011020
    CSI 2.44
    rCSI 10.72%
    PRS 69.31
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.43
    rCSI 5.44%
    PRS 63.88
  • squamous epithelial cell CL0000076
    CSI 2.4
    rCSI 5.7%
    PRS 80.85
  • transit amplifying cell of colon CL0009011
    CSI 2.38
    rCSI 2.8%
    PRS 82.36
  • IgA plasma cell CL0000987
    CSI 2.37
    rCSI 2.43%
    PRS 87.65
  • Mueller cell CL0000636
    CSI 2.36
    rCSI 5.4%
    PRS 72.41
  • respiratory basal cell CL0002633
    CSI 2.21
    rCSI 2.28%
    PRS 84.63
  • OFF midget ganglion cell CL4033047
    CSI 2.2
    rCSI 44.71%
    PRS 71.83
  • conjunctival epithelial cell CL1000432
    CSI 2.18
    rCSI 3.33%
    PRS 80.89
  • hepatocyte CL0000182
    CSI 2.18
    rCSI 3.9%
    PRS 80.02
  • adipocyte CL0000136
    CSI 2.14
    rCSI 2.74%
    PRS 70.92
  • ON midget ganglion cell CL4033046
    CSI 2.1
    rCSI 42.87%
    PRS 70.71
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.06
    rCSI 3.29%
    PRS 84.29
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.93
    rCSI 11.11%
    PRS 77.35
  • colon epithelial cell CL0011108
    CSI 1.9
    rCSI 1.99%
    PRS 78.14
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.83
    rCSI 4.73%
    PRS 76.27
  • glial cell CL0000125
    CSI 1.81
    rCSI 6.89%
    PRS 71.99
  • type B pancreatic cell CL0000169
    CSI 1.78
    rCSI 3.94%
    PRS 80.17
  • blood vessel endothelial cell CL0000071
    CSI 1.77
    rCSI 3.68%
    PRS 77.44
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.76
    rCSI 2.27%
    PRS 64.22
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.76
    rCSI 2.95%
    PRS 62.98
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 1.62
    rCSI 5.83%
    PRS 60.96
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.6
    rCSI 38.69%
    PRS 61.86
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.55
    rCSI 9.13%
    PRS 63.73
  • glandular epithelial cell CL0000150
    CSI 1.54
    rCSI 4.06%
    PRS 91.54
  • direct pathway medium spiny neuron CL4023026
    CSI 1.49
    rCSI 35.79%
    PRS 61.29
  • lung secretory cell CL1000272
    CSI 1.42
    rCSI 3.52%
    PRS 80.64
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.3
    rCSI 2.29%
    PRS 62.41
  • central nervous system neuron CL2000029
    CSI 1.26
    rCSI 9.24%
    PRS 68.33
  • parietal epithelial cell CL1000452
    CSI 1.24
    rCSI 3.32%
    PRS 72.69
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.24
    rCSI 7.72%
    PRS 72.65
  • tracheal goblet cell CL1000329
    CSI 1.23
    rCSI 2.68%
    PRS 87.52
  • BEST4+ enteroycte CL4030026
    CSI 1.22
    rCSI 1.51%
    PRS 81.55
  • intestinal crypt stem cell of colon CL0009043
    CSI 1.22
    rCSI 9.13%
    PRS 89.69
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.22
    rCSI 2.95%
    PRS 61.06
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.21
    rCSI 4.56%
    PRS 63.57
  • glutamatergic neuron CL0000679
    CSI 1.16
    rCSI 2.39%
    PRS 68.13
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.94
    rCSI 2.93%
    PRS 67.05
  • pancreatic ductal cell CL0002079
    CSI 0.93
    rCSI 1.81%
    PRS 83.69
  • blood vessel smooth muscle cell CL0019018
    CSI 0.78
    rCSI 6.36%
    PRS 75.16
  • enterocyte of epithelium of large intestine CL0002071
    CSI 0.69
    rCSI 3.6%
    PRS 85.64
  • luminal cell of prostate epithelium CL0002340
    CSI 0.67
    rCSI 3.59%
    PRS 88.04
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.66
    rCSI 2.07%
    PRS 64.73
  • ON parasol ganglion cell CL4033052
    CSI 0.55
    rCSI 7.77%
    PRS 71.89

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 Sperm associated antigen 1 ([SPAG1](/details-gene/6674)) is a protein-coding gene located on chromosome 8q22.2. Functionally, [SPAG1](/details-gene/6674) is integral to the assembly of the axonemal dynein complex ([GO:0070286](https://www.ebi.ac.uk/QuickGO/term/GO:0070286)), a critical component of motile cilia and flagella. Consistent with this role, expression data reveals that [SPAG1](/details-gene/6674) is a highly significant and specific marker for various ciliated cell types. **Overall**, its highest significance is observed in [ciliated epithelial cells](/details-cell/CL0000067) (CSI: 30.11), [lung ciliated cells](/details-cell/CL1000271) (CSI: 27.41), and [ependymal cells](/details-cell/CL0000065) (CSI: 22.82). Mutations in [SPAG1](/details-gene/6674) have been directly linked to primary ciliary dyskinesia, a genetic disorder characterized by impaired ciliary function ([Link](https://doi.org/10.1016/j.ajhg.2013.07.025)). ## Cellular Roles and Expression Landscape The expression profile of [SPAG1](/details-gene/6674) strongly indicates a specialized function in cells that utilize motile cilia. **Overall**, the gene demonstrates dominant significance in a spectrum of ciliated cell populations. These include [ciliated epithelial cells](/details-cell/CL0000067) lining various tracts, [lung ciliated cells](/details-cell/CL1000271) essential for mucociliary clearance, and [multi-ciliated epithelial cells](/details-cell/CL0005012). Its high significance in [ependymal cells](/details-cell/CL0000065), which line the brain's ventricles and help circulate cerebrospinal fluid, further reinforces this ciliary-centric role. Beyond these major cell types, [SPAG1](/details-gene/6674) is also significantly expressed in progenitor cells like [deuterosomal cells](/details-cell/CL4033044), which are involved in the generation of multiple cilia (ciliogenesis). The gene's original identification as a sperm-associated antigen ([Link](https://pubmed.ncbi.nlm.nih.gov/1299558/)) is consistent with its essential function in building the flagellar axoneme, which is structurally homologous to motile cilia and necessary for sperm motility and fertilization ([GO:0007338](https://www.ebi.ac.uk/QuickGO/term/GO:0007338)). The collective expression data firmly establishes [SPAG1](/details-gene/6674) as a key component of the molecular machinery for cilia and flagella across diverse tissues. ## Pathways and Molecular Function [SPAG1](/details-gene/6674) is primarily associated with the biological process of **axonemal dynein complex assembly** ([GO:0070286](https://www.ebi.ac.uk/QuickGO/term/GO:0070286)). Axonemal dyneins are the motor protein complexes that drive the beating of cilia and flagella. A study by Knowles et al. demonstrated that mutations in [SPAG1](/details-gene/6674) lead to defects in both the outer and inner dynein arms, resulting in the clinical phenotype of primary ciliary dyskinesia ([Link](https://doi.org/10.1016/j.ajhg.2013.07.025)). The gene product localizes to the cytoplasm ([GO:0005737](https://www.ebi.ac.uk/QuickGO/term/GO:0005737)) and is a component of the dynein axonemal particle ([GO:0120293](https://www.ebi.ac.uk/QuickGO/term/GO:0120293)), where it likely acts as a chaperone or assembly factor. Its annotated molecular functions include GTP binding ([GO:0005525](https://www.ebi.ac.uk/QuickGO/term/GO:0005525)) and general hydrolase activity ([GO:0016787](https://www.ebi.ac.uk/QuickGO/term/GO:0016787)), suggesting it may play a regulatory or enzymatic role in the assembly process. This function is indispensable for the cells where it is most highly expressed, such as [lung ciliated cells](/details-cell/CL1000271) that require coordinated ciliary beating to clear pathogens and debris from the airways. ## Research Directions The well-established role of [SPAG1](/details-gene/6674) in ciliary function provides a solid foundation, but its reported involvement in pathology outside of ciliopathies presents intriguing new research avenues. A key study has implicated [SPAG1](/details-gene/6674) in pancreatic tumorigenesis, showing that its expression promotes cancer cell motility ([Link](https://doi.org/10.1038/sj.onc.1209961)). This suggests a pathological co-option of a developmental motility program. Based on this, several testable hypotheses can be proposed: 1. **Hypothesis 1:** The ectopic expression of [SPAG1](/details-gene/6674) in non-ciliated pancreatic ductal cells reactivates a latent cellular motility program, contributing directly to the metastatic potential of pancreatic cancer by altering cytoskeletal dynamics independent of ciliary structures. 2. **Hypothesis 2:** In the context of male infertility, specific [SPAG1](/details-gene/6674) mutations, beyond those causing gross flagellar defects, may subtly impair axonemal dynein regulation, leading to diminished sperm velocity or aberrant swimming patterns that are insufficient for successful fertilization. **Experimental Proposal:** To test Hypothesis 1, one could utilize a pancreatic ductal adenocarcinoma (PDAC) cell line that expresses endogenous [SPAG1](/details-gene/6674), such as PANC-1 or AsPC-1. A CRISPR-Cas9-mediated knockout of [SPAG1](/details-gene/6674) would be generated. The impact on cell motility and invasion could then be quantitatively assessed using in vitro transwell migration and invasion assays. Furthermore, an orthotopic mouse model could be employed, where control and [SPAG1](/details-gene/6674)-knockout PDAC cells are implanted into the pancreas of immunodeficient mice. The subsequent development of primary tumors and the incidence of metastasis to distant organs like the liver and lungs would be monitored and quantified to determine the in vivo contribution of [SPAG1](/details-gene/6674) to cancer progression. **Therapeutic Potential:** Given its role in promoting cancer cell motility, [SPAG1](/details-gene/6674) represents a potential therapeutic target for **inhibition** in cancers where it is aberrantly expressed, such as pancreatic cancer. Its highly restricted expression pattern in healthy adults (primarily confined to ciliated cells and testes) may offer a therapeutic window, potentially reducing off-target toxicity. A small molecule inhibitor or a targeted therapy (e.g., siRNA) designed to downregulate [SPAG1](/details-gene/6674) expression could be investigated as a strategy to suppress metastasis, which is the primary cause of mortality in pancreatic cancer patients.

Genular Protein ID: 3064095333

Symbol: SPAG1_HUMAN

Name: Sperm-associated antigen 1

UniProtKB Accession Codes:

Q07617 A6NP70 B3KQ58 G3XAM3 Q7Z5G1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChEBI 1 ChiTaRS 1 ComplexPortal 2 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 4 GO 9 Gene3D 1 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 4 SASBDB 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11517287

Title: Expression and function of the HSD-3.8 gene encoding a testis-specific protein.

PubMed ID: 11517287

DOI: 10.1093/molehr/7.9.811

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16421571

Title: DNA sequence and analysis of human chromosome 8.

PubMed ID: 16421571

DOI: 10.1038/nature04406

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: 1299558

Title: Isolation and sequencing of the cDNA encoding the 75-kD human sperm protein related to infertility.

PubMed ID: 1299558

PubMed ID: 16983343

Title: Sperm-associated antigen 1 is expressed early in pancreatic tumorigenesis and promotes motility of cancer cells.

PubMed ID: 16983343

DOI: 10.1038/sj.onc.1209961

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 24055112

Title: Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms.

PubMed ID: 24055112

DOI: 10.1016/j.ajhg.2013.07.025

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

Sequence Information:

  • Length: 926
  • Mass: 103639
  • Checksum: 947E460842AD9615
  • Sequence:
    • MTTKDYPSLW GFGTTKTFKI PIEHLDFKYI EKCSDVKHLE KILCVLRSGE EGYYPELTEF 
CEKHLQALAP ESRALRKDKP AATAASFTAE EWEKIDGDIK SWVSEIKKEE DKMHFHETET 
FPAMKDNLPP VRGSNSCLHV GKEKYSKRPT KKKTPRDYAE WDKFDVEKEC LKIDEDYKEK 
TVIDKSHLSK IETRIDTAGL TEKEKDFLAT REKEKGNEAF NSGDYEEAVM YYTRSISALP 
TVVAYNNRAQ AEIKLQNWNS AFQDCEKVLE LEPGNVKALL RRATTYKHQN KLREATEDLS 
KVLDVEPDND LAKKTLSEVE RDLKNSEAAS ETQTKGKRMV IQEIENSEDE EGKSGRKHED 
GGGDKKPAEP AGAARAAQPC VMGNIQKKLT GKAEGGKRPA RGAPQRGQTP EAGADKRSPR 
RASAAAAAGG GATGHPGGGQ GAENPAGLKS QGNELFRSGQ FAEAAGKYSA AIALLEPAGS 
EIADDLSILY SNRAACYLKE GNCSGCIQDC NRALELHPFS MKPLLRRAMA YETLEQYGKA 
YVDYKTVLQI DCGLQLANDS VNRLSRILME LDGPNWREKL SPIPAVPASV PLQAWHPAKE 
MISKQAGDSS SHRQQGITDE KTFKALKEEG NQCVNDKNYK DALSKYSECL KINNKECAIY 
TNRALCYLKL CQFEEAKQDC DQALQLADGN VKAFYRRALA HKGLKNYQKS LIDLNKVILL 
DPSIIEAKME LEEVTRLLNL KDKTAPFNKE KERRKIEIQE VNEGKEEPGR PAGEVSMGCL 
ASEKGGKSSR SPEDPEKLPI AKPNNAYEFG QIINALSTRK DKEACAHLLA ITAPKDLPMF 
LSNKLEGDTF LLLIQSLKNN LIEKDPSLVY QHLLYLSKAE RFKMMLTLIS KGQKELIEQL 
FEDLSDTPNN HFTLEDIQAL KRQYEL