RSPH4A

Chr 6AR

radial spoke head component 4A

Also known as: CILD11, RSHL3, RSPH6B, dJ412I7.1

NCBI Gene: 345895ENSG00000111834UniProt: Q5TD94

This gene encodes a protein that appears to be a component the radial spoke head, as determined by homology to similar proteins in the biflagellate alga Chlamydomonas reinhardtii and other ciliates. Radial spokes, which are regularly spaced along cilia, sperm, and flagella axonemes, consist of a thin 'stalk' and a bulbous 'head' that form a signal transduction scaffold between the central pair of microtubules and dynein. Mutations in this gene cause primary ciliary dyskinesia 1, a disease arising from dysmotility of motile cilia and sperm. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 11MIM #612649
AR
474
ClinVar variants
83
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RSPH4A
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 11 · 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
83 Pathogenic / Likely Pathogenic· 226 VUS of 474 total submissions

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.
0.94LOEUF
pLI 0.000
Z-score 1.83
OE 0.65 (0.46–0.94)
Tolerant

Typical tolerance to LoF variation

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.
0.32Z-score
OE missense 0.95 (0.87–1.04)
354 obs / 371.3 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.0.65 (0.46–0.94)
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 (0.87–1.04)
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.0.96
0≤1.21.6
LoF obs/exp: 21 / 32.2Missense obs/exp: 354 / 371.3Syn Z: 0.32

ClinVar Variant Classifications

474 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic21
VUS226
Likely Benign115
Benign27
Conflicting23
62
Pathogenic
21
Likely Pathogenic
226
VUS
115
Likely Benign
27
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
2
42
2
62
Likely Pathogenic
11
2
8
0
21
VUS
2
203
19
2
226
Likely Benign
0
13
27
75
115
Benign
0
5
22
0
27
Conflicting
—23
Total2922511879474

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

View in ClinVar →

Protein Context — Lollipop Plot

RSPH4A · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ciliary dyskinesia, primary, 11

MIM #612649

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — RSPH4A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
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
The RSPH4A Gene in Primary Ciliary Dyskinesia.
De Jesús-Rojas W et al.·Int J Mol Sci
2023Review
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
Rsph4a is essential for the triplet radial spoke head assembly of the mouse motile cilia.
Yoke H et al.·PLoS Genet
2020Functional
Novel Gene Variants Associated with Primary Ciliary Dyskinesia.
Demir Eksi D et al.·Indian J Pediatr
2022
Analysis of clinical characteristics and histopathological transcription in 40 patients afflicted by epilepsy stemming from focal cortical dysplasia.
Zhang K et al.·Epilepsia Open
2024Cohort
Primary ciliary dyskinesia in a Japanese woman caused by a novel RSPH4A variant.
Ogata R et al.·Respir Investig
2025Case report
RSPH4A-PCDx: An Index to Predict Lung Function Decline in Primary Ciliary Dyskinesia.
Román-Ríos G et al.·Adv Respir Med
2025
Nasal Nitric Oxide Levels: Improving the Diagnosis of Primary Ciliary Dyskinesia in Puerto Rico.
De Jesús-Rojas W et al.·Adv Respir Med
2022
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
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