RSPH9

Chr 6

radial spoke head component 9

Also known as: C6orf206, CILD12, MRPS18AL1

NCBI Gene: 221421ENSG00000172426UniProt: Q9H1X1

This gene encodes a protein thought to be a component of the radial spoke head in motile cilia and flagella. Mutations in this gene are associated with primary ciliary dyskinesia 12. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jul 2010]

Primary Disease Associations & Inheritance

UniProtCiliary dyskinesia, primary, 12
263
ClinVar variants
32
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RSPH9
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 12 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 120 VUS of 263 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.63LOEUF
pLI 0.000
Z-score -0.12
OE 1.04 (0.67–1.63)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.24Z-score
OE missense 0.95 (0.83–1.08)
164 obs / 172.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.04 (0.67–1.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.83–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 13 / 12.6Missense obs/exp: 164 / 172.8Syn Z: 0.18

ClinVar Variant Classifications

263 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic9
VUS120
Likely Benign79
Benign24
Conflicting8
23
Pathogenic
9
Likely Pathogenic
120
VUS
79
Likely Benign
24
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
4
16
0
23
Likely Pathogenic
5
0
4
0
9
VUS
2
110
7
1
120
Likely Benign
0
23
22
34
79
Benign
0
1
21
2
24
Conflicting
—8
Total101387037263

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RSPH9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Genetic Spectrum of Children With Primary Ciliary Dyskinesia in China.
Guan Y et al.·Chest
2021
Motile Ciliary Disorders of the Nasal Epithelium in Adults With Bronchiectasis.
Zhang RL et al.·Chest
2023
LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility.
Hwang JY et al.·Elife
2023
Deficiency in DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice.
Yang M et al.·Elife
2025
From a single whole exome read to notions of clinical screening: primary ciliary dyskinesia and RSPH9 p.Lys268del in the Arabian Peninsula.
Alsaadi MM et al.·Ann Hum Genet
2012
RSPH9 methylation pattern as a prognostic indicator in patients with non-muscle invasive bladder cancer.
Yoon HY et al.·Oncol Rep
2016Cohort
Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities.
Castleman VH et al.·Am J Hum Genet
2009
Exploring nasopharyngeal carcinoma genetics: Bioinformatics insights into pathways and gene associations.
Che Ismail CL et al.·Med J Malaysia
2024Review
Founder mutation(s) in the RSPH9 gene leading to primary ciliary dyskinesia in two inbred Bedouin families.
Reish O et al.·Ann Hum Genet
2010
Mutations in radial spoke head genes and ultrastructural cilia defects in East-European cohort of primary ciliary dyskinesia patients.
Ziętkiewicz E et al.·PLoS One
2012Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Mapping the Most Common Founder Variant in RSPH9 That Causes Primary Ciliary Dyskinesia in Multiple Consanguineous Families of Bedouin Arabs.
Al-Mutairi DA et al.·J Clin Med
2023🔓 Open Access
Pathogenic gene variants in CCDC39, CCDC40, RSPH1, RSPH9, HYDIN, and SPEF2 cause defects of sperm flagella composition and male infertility.
Aprea I et al.·Front Genet
2023🔓 Open Access
Combining RSPH9 founder mutation screening and next-generation sequencing analysis is efficient for primary ciliary dyskinesia diagnosis in Saudi patients.
Mabrouk I et al.·J Hum Genet
2022Cohort
Loss of Rsph9 causes neonatal hydrocephalus with abnormal development of motile cilia in mice.
Zou W et al.·Sci Rep
2020🔓 Open Access
Wide phenotypic variability in RSPH9-associated primary ciliary dyskinesia: review of a case-series from Cyprus.
Yiallouros PK et al.·J Thorac Dis
2019Review
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools