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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SPAG17
sperm associated antigen 17
Chromosome 1 Β· 1p12
NCBI Gene: 200162Ensembl: ENSG00000155761.14HGNC: HGNC:26620UniProt: Q6Q759
38PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
epithelial cilium movement involved in extracellular fluid movementspermatogenesismotile cilium assemblyaxonemal central apparatus assemblyosteoarthritis, hipandrogenetic alopeciaspermatogenic failure 55Abnormality of the skeletal system
✦AI Summary

SPAG17 encodes a critical component of the central pair apparatus in motile cilia, essential for proper ciliary structure and function 1. The protein is required for sperm flagellum development and assembly of respiratory motile cilia central pair apparatus, but appears dispensable for brain ependymal cilia 1. SPAG17 plays a crucial role in male fertility, as homozygous mutations cause severe asthenozoospermia through multiple morphological abnormalities of spermatozoal flagella (MMAF), including incomplete C1a projections and missing microtubule doublets 23. Beyond reproductive function, SPAG17 regulates skeletal development and bone formation. Spag17-deficient mice exhibit skeletal malformations, altered limb patterning, and premature ossification, likely due to its role in primary cilia of chondrocytes and osteoblasts 4. Interestingly, SPAG17 also functions as a negative regulator of fibrosis - reduced expression in systemic sclerosis patients correlates with myofibroblast activation and skin fibrosis 5. Loss-of-function mutations cause primary ciliary dyskinesia with respiratory dysfunction and hydrocephalus in mice 1, while in humans they primarily manifest as male infertility that can be treated with ICSI and assisted oocyte activation 3.

Sources cited
1
SPAG17 is essential for sperm flagellum development and respiratory motile cilia but not brain ependymal cilia, and mutations cause primary ciliary dyskinesia phenotypes
PMID: 32988999
2
Homozygous SPAG17 mutations cause severe asthenozoospermia with MMAF, including incomplete C1a projections and missing microtubule doublets
PMID: 39686771
3
SPAG17 mutations cause familial severe asthenozoospermia that can be treated with ICSI and assisted oocyte activation
PMID: 41070644
4
Spag17 deficiency causes skeletal malformations, altered bone formation, and shorter primary cilia in chondrocytes and osteoblasts
PMID: 26017218
5
Reduced SPAG17 expression in systemic sclerosis correlates with myofibroblast activation and drives fibrosis
PMID: 36116512
Disease Associationsβ“˜21
osteoarthritis, hipOpen Targets
0.50Moderate
androgenetic alopeciaOpen Targets
0.44Moderate
spermatogenic failure 55Open Targets
0.43Moderate
Abnormality of the skeletal systemOpen Targets
0.43Moderate
total hip arthroplastyOpen Targets
0.40Weak
alopeciaOpen Targets
0.39Weak
male infertility with azoospermia or oligozoospermia due to single gene mutationOpen Targets
0.38Weak
non-syndromic male infertility due to sperm motility disorderOpen Targets
0.37Weak
adolescent idiopathic scoliosisOpen Targets
0.32Weak
goiterOpen Targets
0.32Weak
thyroid cancerOpen Targets
0.32Weak
facial morphologyOpen Targets
0.30Weak
heart diseaseOpen Targets
0.29Weak
Breast hypertrophyOpen Targets
0.29Weak
alcohol drinkingOpen Targets
0.29Weak
joint diseaseOpen Targets
0.28Weak
cranioectodermal dysplasiaOpen Targets
0.27Weak
smoking behaviorOpen Targets
0.26Weak
sinusitisOpen Targets
0.23Weak
Hammer Toe SyndromeOpen Targets
0.21Weak
Spermatogenic failure 55UniProt
Pathogenic Variants2
NM_206996.4(SPAG17):c.1069G>C (p.Asp357His)Likely pathogenic
Cranioectodermal dysplasia 2|Meniere disease
β˜…β˜†β˜†β˜†2017β†’ Residue 357
NM_206996.4(SPAG17):c.4343G>A (p.Arg1448Gln)Pathogenic
Spermatogenic failure 55
β˜†β˜†β˜†β˜†2021β†’ Residue 1448
View on ClinVar β†—
Related Genes
SPAG6Protein interaction93%LRGUKProtein interaction90%CFAP221Protein interaction85%DNAI1Protein interaction72%SPEF2Protein interaction54%AXDND1Shared pathway40%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
90%
Ovary
45%
Brain
28%
Liver
17%
Heart
0%
Gene Interaction Network
Click a node to explore
SPAG17SPAG6LRGUKCFAP221DNAI1SPEF2AXDND1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6Q759
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.69LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.60 [0.52–0.69]
RankingsWhere SPAG17 stands among ~20K protein-coding genes
  • #10,547of 20,598
    Most Researched38
  • #4,475of 5,498
    Most Pathogenic Variants2
  • #5,233of 17,882
    Most Constrained (LOEUF)0.69
Genes detectedSPAG17
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Alterations of the Primary Cilia Gene SPAG17 and SOX9 Locus Noncoding RNAs Identified by RNA-Sequencing Analysis in Patients With Systemic Sclerosis.
PMID: 35762854
Arthritis Rheumatol Β· 2023
1.00
2
Reduced SPAG17 Expression in Systemic Sclerosis Triggers Myofibroblast Transition and Drives Fibrosis.
PMID: 36116512
J Invest Dermatol Β· 2023
0.90
3
[Identification and clinical implication of a novel variant of SPAG17 gene resulting in Familial severe asthenozoospermia].
PMID: 41070644
Zhonghua Yi Xue Yi Chuan Xue Za Zhi Β· 2025
0.80
4
Novel homozygous SPAG17 variants cause human male infertility through multiple morphological abnormalities of spermatozoal flagella related to axonemal microtubule doublets.
PMID: 39686771
Asian J Androl Β· 2025
0.70
5
Exploring hypoxia- and cuproptosis-related biomarkers in periodontitis based on transcriptome and single-cell analysis.
PMID: 41460373
Clin Oral Investig Β· 2025
0.60