SPAG1 Gene

HGNC Family	Tetratricopeptide repeat domain containing (TTC)
Name	sperm associated antigen 1
Description	The correlation of anti-sperm antibodies with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as identification of proteins for targeted contraception, are dependent on the identification and characterization of relevant sperm antigens. The protein expressed by this gene is recognized by anti-sperm agglutinating antibodies from an infertile woman. Furthermore, immunization of female rats with the recombinant human protein reduced fertility. This protein localizes to the plasma membrane of germ cells in the testis and to the post-acrosomal plasma membrane of mature spermatozoa. Recombinant polypeptide binds GTP and exhibits GTPase activity. Thus, this protein may regulate GTP signal transduction pathways involved in spermatogenesis and fertilization. Two transcript variants of this gene encode the same protein. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPAG1 is emerging as a key cytoplasmic factor required for the proper assembly and function of motile cilia. Mutations in SPAG1 result in primary ciliary dyskinesia by impairing the cytoplasmic assembly and/or trafficking of axonemal dynein arms—specifically the outer and inner dynein arms—thereby disrupting ciliary beating and causing laterality defects. Biochemical investigations have established that SPAG1 functions as a multidomain scaffold that assembles chaperones, including HSP70 and HSP90, together with other dynein assembly factors (DNAAFs) as part of an R2TP‐like complex to facilitate proper dynein arm formation and stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in ciliary function, SPAG1 was originally identified as a sperm antigen and is expressed prominently in testicular tissue. Early studies characterizing the human sperm antigen gene revealed that SPAG1 is localized throughout the sperm cell—from the head to the tail—and participates in the fertilization process, suggesting a critical contribution to spermatogenesis and/or gamete function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, aberrant expression and gene amplification of SPAG1 have been implicated in oncogenesis. Elevated SPAG1 levels are observed in malignancies such as pancreatic ductal adenocarcinoma, where its cytoplasmic localization and association with microtubules correlate with enhanced cancer cell motility and early tumor spread. Increased SPAG1 gene copy number has additionally been linked to decreased survival in prostate cancer, and recent work in acute myeloid leukemia demonstrates that SPAG1 promotes cell proliferation and survival—at least in part by modulating the ERK/MAPK signaling pathway. These observations highlight a potential role for SPAG1 not only in normal ciliary and sperm functions but also in tumor progression and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael R Knowles, Lawrence E Ostrowski, Niki T Loges, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2013.07.025"}], "href": "https://doi.org/10.1016/j.ajhg.2013.07.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24055112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24055112"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marie-Eve Chagot, Raphael Dos Santos Morais, Sana Dermouche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Binding properties of the quaternary assembly protein SPAG1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20190198"}], "href": "https://doi.org/10.1042/BCJ20190198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31118266"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31118266"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sana Dermouche, Marie-Eve Chagot, Xavier Manival, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Optimizing the First TPR Domain of the Human SPAG1 Protein Provides Insight into the HSP70 and HSP90 Binding Properties."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.biochem.1c00052"}], "href": "https://doi.org/10.1021/acs.biochem.1c00052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33739091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33739091"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ri-Ichiro Kanazawa, Shinji Komori, Kazuko Sakata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Isolation and characterization of a human sperm antigen gene h-Sp-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Androl (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1365-2605.2003.00418.x"}], "href": "https://doi.org/10.1046/j.1365-2605.2003.00418.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12846798"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12846798"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "A Neesse, R Gangeswaran, J Luettges, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sperm-associated antigen 1 is expressed early in pancreatic tumorigenesis and promotes motility of cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1209961"}], "href": "https://doi.org/10.1038/sj.onc.1209961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16983343"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16983343"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Elham Shamsara, Jamal Shamsara "}, {"type": "b", "children": [{"type": "t", "text": "Bioinformatics analysis of the genes involved in the extension of prostate cancer to adjacent lymph nodes by supervised and unsupervised machine learning methods: The role of SPAG1 and PLEKHF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genomics (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygeno.2020.06.035"}], "href": "https://doi.org/10.1016/j.ygeno.2020.06.035"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32619574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32619574"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yu Gu, Ming-Qiang Chu, Zi-Jun Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive analysis of SPAG1 expression as a prognostic and predictive biomarker in acute myeloid leukemia by integrative bioinformatics and clinical validation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genomics (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12920-022-01193-0"}], "href": "https://doi.org/10.1186/s12920-022-01193-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35227274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35227274"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lu Liu, Jing Liu, Xiao-Jun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPAG1 promotes the development of AML by activating the ERK/MAPK signaling pathway and affects the chemotherapy sensitivity of venetoclax."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasma (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/neo_2022_220415N416"}], "href": "https://doi.org/10.4149/neo_2022_220415N416"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35951456"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35951456"}]}]}]}
Synonyms	HEL-S-268, CILD28, HSD-3.8, SP75, TPIS, CT140
Proteins	SPAG1_HUMAN
NCBI Gene ID	6674
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SPAG1 has 6,008 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for SPAG1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SPAG1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SPAG1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SPAG1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SPAG1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SPAG1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SPAG1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SPAG1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SPAG1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SPAG1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SPAG1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SPAG1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SPAG1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SPAG1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SPAG1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SPAG1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPAG1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SPAG1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SPAG1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with SPAG1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SPAG1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing SPAG1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SPAG1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SPAG1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SPAG1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SPAG1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing SPAG1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SPAG1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SPAG1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SPAG1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SPAG1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SPAG1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SPAG1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SPAG1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving SPAG1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SPAG1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SPAG1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SPAG1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SPAG1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SPAG1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SPAG1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPAG1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.