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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SPAG1
sperm associated antigen 1
Chromosome 8 Β· 8q22.2
NCBI Gene: 6674Ensembl: ENSG00000104450.14HGNC: HGNC:11212UniProt: Q07617
50PubMed Papers
21Diseases
0Drugs
69Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytosolcytoplasmaxonemal dynein complex assemblysingle fertilizationprimary ciliary dyskinesiaautosomal dominant nocturnal frontal lobe epilepsy 5autosomal dominant nocturnal frontal lobe epilepsyKartagener Syndrome
✦AI Summary

SPAG1 (sperm associated antigen 1) is a multidomain protein that serves as a critical dynein axonemal assembly factor (DNAAF) required for proper ciliary function 1. Its primary function involves facilitating the cytoplasmic assembly of dynein arms before their transport into cilia, where it scaffolds R2TP-like complexes composed of several DNAAFs that enable folding and binding of dynein heavy chains to dynein intermediate chain complexes 1. The protein contains multiple tetratricopeptide repeat (TPR) domains that mediate protein-protein interactions with chaperones including HSP70 and HSP90, as well as components of the R2TP complex 12. SPAG1 mutations cause primary ciliary dyskinesia (PCD), a heterogeneous disorder characterized by chr8 respiratory disease, infertility, and laterality defects 34. In PCD patients, SPAG1 deficiency results in reduced protein levels of dynein heavy chains and impaired interactions between dynein components 1. Interestingly, SPAG1 expression has also been implicated in acute myeloid leukemia, where overexpression correlates with poor prognosis and promotes cell proliferation through ERK/MAPK pathway activation 56. A 60 kDa SPAG1 isoform can partially compensate for full-length protein absence, assembling reduced numbers of outer dynein arms 1.

Sources cited
1
SPAG1 functions as a dynein axonemal assembly factor that scaffolds R2TP-like complexes and interacts with DNAAFs, dynein chains, and chaperones
PMID: 35178554
2
SPAG1 contains TPR domains that interact with HSP70 and HSP90 chaperones
PMID: 31118266
3
SPAG1 mutations are associated with primary ciliary dyskinesia in pediatric patients
PMID: 33577779
4
SPAG1 variants found in Indian PCD patients expanding the genetic spectrum
PMID: 39004944
5
SPAG1 overexpression in acute myeloid leukemia correlates with poor prognosis
PMID: 35227274
6
SPAG1 promotes AML development through ERK/MAPK signaling pathway activation
PMID: 35951456
Disease Associationsβ“˜21
primary ciliary dyskinesiaOpen Targets
0.77Strong
autosomal dominant nocturnal frontal lobe epilepsyOpen Targets
0.45Moderate
autosomal dominant nocturnal frontal lobe epilepsy 5Open Targets
0.45Moderate
Kartagener SyndromeOpen Targets
0.33Weak
complex regional pain syndromeOpen Targets
0.28Weak
pleural empyemaOpen Targets
0.23Weak
pneumothoraxOpen Targets
0.23Weak
rheumatoid arthritisOpen Targets
0.21Weak
ACPA-positive rheumatoid arthritisOpen Targets
0.20Weak
Abnormality of the genital systemOpen Targets
0.19Weak
male reproductive organ cancerOpen Targets
0.13Weak
genetic disorderOpen Targets
0.12Weak
acute myeloid leukemiaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
benign prostatic hyperplasiaOpen Targets
0.07Suggestive
lung adenocarcinomaOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
cutaneous melanomaOpen Targets
0.03Suggestive
exostosisOpen Targets
0.02Suggestive
triple-negative breast cancerOpen Targets
0.02Suggestive
Ciliary dyskinesia, primary, 28UniProt
Pathogenic Variants69
NM_003114.5(SPAG1):c.2014C>T (p.Gln672Ter)Pathogenic
Autosomal dominant nocturnal frontal lobe epilepsy 5|Kartagener syndrome|Primary ciliary dyskinesia 28|Primary ciliary dyskinesia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 672
NM_003114.5(SPAG1):c.897_901del (p.Lys301fs)Pathogenic
not provided|Primary ciliary dyskinesia 28|Primary ciliary dyskinesia
β˜…β˜…β˜†β˜†2025β†’ Residue 301
NM_003114.5(SPAG1):c.1097-11C>GPathogenic
Primary ciliary dyskinesia 28|not provided
β˜…β˜…β˜†β˜†2025
NM_003114.5(SPAG1):c.1119del (p.Ala374fs)Pathogenic
Primary ciliary dyskinesia 28|Primary ciliary dyskinesia
β˜…β˜…β˜†β˜†2025β†’ Residue 374
NM_003114.5(SPAG1):c.1285_1294del (p.Gly429fs)Pathogenic
Primary ciliary dyskinesia|SPAG1-related disorder|Primary ciliary dyskinesia 28
β˜…β˜…β˜†β˜†2025β†’ Residue 429
NM_003114.5(SPAG1):c.2089C>T (p.Arg697Ter)Pathogenic
not provided|Primary ciliary dyskinesia 28
β˜…β˜…β˜†β˜†2025β†’ Residue 697
NM_003114.5(SPAG1):c.2367del (p.Ser789fs)Pathogenic
Primary ciliary dyskinesia 28|SPAG1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 789
NM_003114.5(SPAG1):c.939+1G>ALikely pathogenic
Primary ciliary dyskinesia 28
β˜…β˜…β˜†β˜†2024
NM_003114.5(SPAG1):c.1113_1149del (p.Gly372fs)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜…β˜†β˜†2024β†’ Residue 372
NM_003114.5(SPAG1):c.1282_1294del (p.Ala428fs)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜…β˜†β˜†2022β†’ Residue 428
NM_003114.5(SPAG1):c.1282_1294dup (p.Ala432fs)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜†β˜†β˜†2026β†’ Residue 432
NM_003114.5(SPAG1):c.134del (p.Val45fs)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜†β˜†β˜†2025β†’ Residue 45
NM_003114.5(SPAG1):c.237dup (p.Pro80fs)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜†β˜†β˜†2025β†’ Residue 80
GRCh38/hg38 8q22.2(chr8:100138992-100172318)x1Likely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2025
NM_003114.5(SPAG1):c.217del (p.Arg73fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 73
NM_003114.5(SPAG1):c.1497_1500del (p.Gly501fs)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜†β˜†β˜†2025β†’ Residue 501
NM_003114.5(SPAG1):c.261del (p.Phe87fs)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜†β˜†β˜†2025β†’ Residue 87
NM_003114.5(SPAG1):c.614del (p.Lys205fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 205
NM_003114.5(SPAG1):c.997C>T (p.Gln333Ter)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜†β˜†β˜†2025β†’ Residue 333
NM_003114.5(SPAG1):c.1864dup (p.Thr622fs)Pathogenic
Primary ciliary dyskinesia 28
β˜…β˜†β˜†β˜†2025β†’ Residue 622
View on ClinVar β†—
Related Genes
RSPH9Protein interaction100%RUVBL2Protein interaction100%RUVBL1Protein interaction100%RSPH1Protein interaction99%DNAI2Protein interaction96%DNAAF1Protein interaction94%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
23%
Liver
19%
Lung
14%
Heart
8%
Ovary
5%
Gene Interaction Network
Click a node to explore
SPAG1RSPH9RUVBL2RUVBL1RSPH1DNAI2DNAAF1
PROTEIN STRUCTURE
Preparing viewer…
PDB6I57 Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.08LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.83 [0.64–1.08]
RankingsWhere SPAG1 stands among ~20K protein-coding genes
  • #8,883of 20,598
    Most Researched50
  • #1,057of 5,498
    Most Pathogenic Variants69 Β· top quartile
  • #11,025of 17,882
    Most Constrained (LOEUF)1.08
Genes detectedSPAG1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China.
PMID: 33577779
Chest Β· 2021
1.00
2
Genetics of 67 patients of suspected primary ciliary dyskinesia from India.
PMID: 39004944
Clin Genet Β· 2024
0.90
3
Optimizing the First TPR Domain of the Human SPAG1 Protein Provides Insight into the HSP70 and HSP90 Binding Properties.
PMID: 33739091
Biochemistry Β· 2021
0.80
4
Immune cell-based transcriptomic Mendelian randomization and colocalization study on type 1 diabetes.
PMID: 41299435
BMC Med Β· 2025
0.70
5
The role of SPAG1 in the assembly of axonemal dyneins in human airway epithelia.
PMID: 35178554
J Cell Sci Β· 2022
0.60