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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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RSPH6A
radial spoke head 6 homolog A
Chromosome 19 · 19q13.32
NCBI Gene: 81492Ensembl: ENSG00000104941.8HGNC: HGNC:14241UniProt: Q9H0K4
17PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcilium movementaxoneme assemblymanchette disassemblyneurodegenerative diseasecoronary artery diseaseazoospermiaheart failure
✦AI Summary

RSPH6A (radial spoke head 6 homolog A) is a structural component of the radial spoke complex within the axoneme of sperm flagella. It functions as part of the radial spoke head, a T-shaped macromolecular complex that connects peripheral doublet microtubules to the central pair apparatus to regulate sperm flagellar beat frequency and amplitude 1. RSPH6A is testis-enriched and essential for proper flagellar assembly and male fertility; Rsph6a knockout mice produce short, immotile spermatozoa due to disrupted axoneme elongation and impaired manchette removal, with secondary loss of RSPH9 in flagella 2. Reduced RSPH6A expression is associated with asthenozoospermia (reduced sperm motility) 3. Genetic mutations in RSPH6A cause male infertility with normal sperm morphology in humans 4, and RSPH6A is a critical component of the radial spoke 1 head structure 1. Beyond fertility, RSPH6A variants show potential associations with blood pressure regulation through DNA methylation-mediated pathways 5 and shared genetic relationships with migraine and thyroid function traits 6. Testis-specific hypomethylation of RSPH6A supports tissue-specific expression patterns 7.

Sources cited
1
RSPH6A is testis-enriched, localized in flagella, and essential for sperm flagellar assembly; Rsph6a knockout causes infertility with short immotile sperm and disrupted axoneme elongation
PMID: 30185526
2
RSPH6A is a critical component of radial spoke 1 head; connects peripheral doublet microtubules to central pair; RSPH6A deficiency causes asthenozoospermia with normal morphology in humans and mice
PMID: 39849482
3
RSPH6A expression is reduced in asthenozoospermic patients and correlates with reduced sperm motility
PMID: 35886074
4
CpGs mapped to RSPH6A are significantly associated with diastolic blood pressure levels in mediation analysis
PMID: 38291711
5
RSPH6A is a significant gene in cross-trait GWAS analysis of migraine and thyroid-stimulating hormone
PMID: 36739509
6
RSPH6A shows testis/sperm-specific hypomethylation associated with testis-specific expression
PMID: 26756355
7
RSPH6A mutations cause male infertility phenotype in humans; this is the first documentation of RSPH6A role in human male infertility
PMID: 38884051
8
Rsph6a is absent from the murine radial spoke head core complex, distinguishing mouse from protozoan radial spoke composition
PMID: 34871179
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.28Weak
coronary artery diseaseOpen Targets
0.11Weak
azoospermiaOpen Targets
0.11Weak
heart failureOpen Targets
0.10Suggestive
hypertrophic cardiomyopathyOpen Targets
0.09Suggestive
spermatogenic failure 72Open Targets
0.09Suggestive
spermatogenic failure, X-linked, 5Open Targets
0.09Suggestive
spermatogenic failure 18Open Targets
0.09Suggestive
spermatogenic failure 27Open Targets
0.09Suggestive
spermatogenic failure 46Open Targets
0.09Suggestive
spermatogenic failure 19Open Targets
0.09Suggestive
spermatogenic failure 43Open Targets
0.09Suggestive
spermatogenic failure 45Open Targets
0.09Suggestive
spermatogenic failure 49Open Targets
0.09Suggestive
spermatogenic failure 82Open Targets
0.09Suggestive
spermatogenic failure 65Open Targets
0.09Suggestive
spermatogenic failure 24Open Targets
0.08Suggestive
spermatogenic failure 51Open Targets
0.08Suggestive
spermatogenic failure 84Open Targets
0.08Suggestive
spermatogenic failure 93Open Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
RSPH3Protein interaction93%DMWDProtein interaction90%RSPH1Protein interaction86%RANBP2Protein interaction81%RSPH9Protein interaction80%RSU1Protein interaction76%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
100%
Brain
50%
Liver
0%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
RSPH6ARSPH3DMWDRSPH1RANBP2RSPH9RSU1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9H0K4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.91LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.72 [0.57–0.91]
RankingsWhere RSPH6A stands among ~20K protein-coding genes
  • #15,106of 20,598
    Most Researched17
  • #8,229of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedRSPH6A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins.
PMID: 38291711
Twin Res Hum Genet · 2024
1.00
2
RSPH6A is required for sperm flagellum formation and male fertility in mice.
PMID: 30185526
J Cell Sci · 2018
0.90
3
Shared genetics and causal relationships between migraine and thyroid function traits.
PMID: 36739509
Cephalalgia · 2023
0.80
4
IQUB mutation induces radial spoke 1 deficiency causing asthenozoospermia with normal sperm morphology in humans and mice.
PMID: 39849482
Cell Commun Signal · 2025
0.70
5
Further Insights on RNA Expression and Sperm Motility.
PMID: 35886074
Genes (Basel) · 2022
0.60