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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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RSPH1
radial spoke head component 1
Chromosome 21 Β· 21q22.3
NCBI Gene: 89765Ensembl: ENSG00000160188.11HGNC: HGNC:12371UniProt: Q8WYR4
23PubMed Papers
21Diseases
0Drugs
27Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleuscytosolmotile ciliumaxoneme assemblyprimary ciliary dyskinesiavitreous body diseaseneurodegenerative diseasegenetic disorder
✦AI Summary

RSPH1 (radial spoke head component 1) is a structural protein essential for ciliary and sperm motility, functioning as a core component of axonemal radial spoke head complexes 1. The radial spoke head consists of RSPH1 alongside RSPH3b, RSPH4a, and RSPH9, forming a brake pad-shaped structure that contacts the central pair apparatus to coordinate ciliary beating 2. RSPH1 mutations cause primary ciliary dyskinesia (PCD), an inherited respiratory disease characterized by defective mucociliary clearance and infertility 1. Loss-of-function RSPH1 mutations result in central pair agenesis with distinctive central pair microtubule instability and loss of the entire radial spoke head structure, including degradation of RSPH4A and RSPH9 13. Cryo-electron tomography reveals that RSPH1-mutant cilia display previously unknown primary structural defects and heterogeneous secondary defects 3. Clinically, RSPH1-PCD patients typically present with normal body laterality and less severe lung disease compared to other PCD variants, possibly due to residual ciliary motility 4. Immunofluorescence analysis effectively diagnoses RSPH1 defects, which can result from loss-of-function mutations or missense variants 5. Beyond ciliary dysfunction, RSPH1 has been identified as a regulator of GSTA1 expression in cancer cell drug tolerance contexts 6, and variants have been associated with disorders of sex development 7.

Sources cited
1
RSPH1 mutations cause primary ciliary dyskinesia with central pair agenesis and loss of radial spoke head structure
PMID: 24518672
2
RSPH1 is a core component of the murine radial spoke head complex with specific structural interactions
PMID: 34871179
3
RSPH1-mutant human cilia show central pair microtubule instability revealed by cryo-electron tomography
PMID: 25473808
4
RSPH1-PCD is associated with less severe lung disease compared to other PCD variants
PMID: 40948093
5
RSPH1 mutations include missense variants and loss-of-function mutations detectable by immunofluorescence
PMID: 25789548
6
RSPH1 regulates GSTA1 expression in cancer drug-tolerant persister cells
PMID: 41076079
7
RSPH1 variants are associated with disorders of sex development
PMID: 41533173
Disease Associationsβ“˜21
primary ciliary dyskinesiaOpen Targets
0.76Strong
vitreous body diseaseOpen Targets
0.29Weak
neurodegenerative diseaseOpen Targets
0.23Weak
genetic disorderOpen Targets
0.19Weak
azoospermiaOpen Targets
0.09Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spermatogenic failure 54Open Targets
0.06Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.06Suggestive
spermatogenic failure 65Open Targets
0.06Suggestive
spermatogenic failure 78Open Targets
0.06Suggestive
spermatogenic failure 84Open Targets
0.06Suggestive
spermatogenic failure 93Open Targets
0.06Suggestive
spermatogenic failure 40Open Targets
0.06Suggestive
spermatogenic failure 39Open Targets
0.06Suggestive
spermatogenic failure 72Open Targets
0.06Suggestive
spermatogenic failure 76Open Targets
0.06Suggestive
spermatogenic failure 80Open Targets
0.06Suggestive
spermatogenic failure 20Open Targets
0.06Suggestive
spermatogenic failure 92Open Targets
0.06Suggestive
spermatogenic failure 94Open Targets
0.06Suggestive
Ciliary dyskinesia, primary, 24UniProt
Pathogenic Variants27
NM_080860.4(RSPH1):c.275-2A>CPathogenic
Primary ciliary dyskinesia 24|Kartagener syndrome|Primary ciliary dyskinesia|not provided|RSPH1-related disorder|Ovarian serous cystadenocarcinoma|Familial cancer of breast
β˜…β˜…β˜†β˜†2026
NM_080860.4(RSPH1):c.85G>T (p.Glu29Ter)Pathogenic
Primary ciliary dyskinesia 24|Kartagener syndrome|Primary ciliary dyskinesia|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 29
NM_080860.4(RSPH1):c.196C>T (p.Arg66Ter)Pathogenic
Primary ciliary dyskinesia|Primary ciliary dyskinesia 24
β˜…β˜…β˜†β˜†2025β†’ Residue 66
NM_080860.4(RSPH1):c.281G>A (p.Trp94Ter)Pathogenic
Primary ciliary dyskinesia 24|Primary ciliary dyskinesia|RSPH1-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 94
NM_080860.4(RSPH1):c.563T>G (p.Leu188Ter)Pathogenic
Primary ciliary dyskinesia|Primary ciliary dyskinesia 24
β˜…β˜…β˜†β˜†2023β†’ Residue 188
NM_080860.4(RSPH1):c.287dup (p.Asn96fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 96
NM_080860.4(RSPH1):c.1A>C (p.Met1Leu)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 1
NM_080860.4(RSPH1):c.655del (p.Leu219fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 219
NM_080860.4(RSPH1):c.1A>T (p.Met1Leu)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 1
NM_080860.4(RSPH1):c.287_305dup (p.His102delinsGlnTer)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025β†’ Residue 102
NM_080860.4(RSPH1):c.54+2T>CLikely pathogenic
Ovarian serous cystadenocarcinoma|Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2025
NM_080860.4(RSPH1):c.544C>T (p.Gln182Ter)Pathogenic
Respiratory ciliopathies including non-CF bronchiectasis
β˜…β˜†β˜†β˜†2024β†’ Residue 182
NM_080860.4(RSPH1):c.655dup (p.Leu219fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2024β†’ Residue 219
NM_080860.4(RSPH1):c.365+2T>CLikely pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2024
NM_080860.4(RSPH1):c.366-3C>APathogenic
Primary ciliary dyskinesia 24|Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2023
NM_080860.4(RSPH1):c.680dup (p.Pro228fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2023β†’ Residue 228
NM_080860.4(RSPH1):c.790_791del (p.Met264fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2022β†’ Residue 264
NM_080860.4(RSPH1):c.390C>A (p.Tyr130Ter)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2022β†’ Residue 130
NM_080860.4(RSPH1):c.634dup (p.Thr212fs)Pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2022β†’ Residue 212
NM_080860.4(RSPH1):c.502-1G>ALikely pathogenic
Primary ciliary dyskinesia
β˜…β˜†β˜†β˜†2022
View on ClinVar β†—
Related Genes
DNAH5Protein interaction99%SPAG1Protein interaction99%DNALI1Protein interaction99%DNAH11Protein interaction99%DNAI1Protein interaction99%ZMYND10Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
85%
Lung
30%
Ovary
27%
Liver
11%
Heart
0%
Gene Interaction Network
Click a node to explore
RSPH1DNAH5SPAG1DNALI1DNAH11DNAI1ZMYND10
PROTEIN STRUCTURE
Preparing viewer…
PDB8J07 Β· 4.10 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.81LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.53 [0.36–0.81]
RankingsWhere RSPH1 stands among ~20K protein-coding genes
  • #13,508of 20,598
    Most Researched23
  • #1,922of 5,498
    Most Pathogenic Variants27
  • #6,804of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedRSPH1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Targeted NGS gene panel identifies mutations in RSPH1 causing primary ciliary dyskinesia and a common mechanism for ciliary central pair agenesis due to radial spoke defects.
PMID: 24518672
Hum Mol Genet Β· 2014
1.00
2
Primary ciliary dyskinesia phenotypes and correlation with genotype.
PMID: 40948093
Curr Opin Pulm Med Β· 2025
0.90
3
GSTA1 Conferred Tolerance to Osimertinib and Provided Strategies to Overcome Drug-Tolerant Persister in EGFR-Mutant Lung Adenocarcinoma.
PMID: 41076079
J Thorac Oncol Β· 2026
0.80
4
Disorders of sex development associated with MPI and RSPH1 variants expand the phenotypic spectrum of CDG and PCD in Morocco.
PMID: 41533173
Mol Biol Rep Β· 2026
0.70
5
Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia.
PMID: 25473808
Nat Commun Β· 2014
0.60