RSPH3

Chr 6

radial spoke head 3

Also known as: CILD32, RSHL2, RSP3, dJ111C20.1

NCBI Gene: 83861ENSG00000130363UniProt: Q86UC2

The protein encoded by this gene acts as a protein kinase A anchoring protein. Mutations in this gene cause primary ciliary dyskinesia; a disorder characterized by defects of the axoneme in motile cilia and sperm flagella. The homolog of this gene was first identified in the blue-green algae Chlamydomonas as encoding a radial spoke protein that formed a structural component of motile cilia and flagella. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Dec 2016]

Primary Disease Associations & Inheritance

UniProtCiliary dyskinesia, primary, 32
388
ClinVar variants
59
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RSPH3
🧬
Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 32 · 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
59 Pathogenic / Likely Pathogenic· 162 VUS of 388 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.
0.93LOEUF
pLI 0.000
Z-score 1.82
OE 0.61 (0.40–0.93)
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.
0.07Z-score
OE missense 0.99 (0.90–1.09)
316 obs / 319.4 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.0.61 (0.40–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.90–1.09)
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.1.08
0≤1.21.6
LoF obs/exp: 15 / 24.8Missense obs/exp: 316 / 319.4Syn Z: -0.72

ClinVar Variant Classifications

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic10
VUS162
Likely Benign130
Benign31
Conflicting6
49
Pathogenic
10
Likely Pathogenic
162
VUS
130
Likely Benign
31
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
37
0
49
Likely Pathogenic
7
0
3
0
10
VUS
4
147
11
0
162
Likely Benign
0
15
34
81
130
Benign
0
9
16
6
31
Conflicting
—6
Total2317110187388

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

View in ClinVar →

Protein Context — Lollipop Plot

RSPH3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RSPH3-related primary ciliary dyskinesia with central-complex defects

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — RSPH3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes.
Jeanson L et al.·Am J Hum Genet
2015
Patients with severe asthenoteratospermia carrying SPAG6 or RSPH3 mutations have a positive pregnancy outcome following intracytoplasmic sperm injection.
Wu H et al.·J Assist Reprod Genet
2020Cohort
IQUB deficiency causes male infertility by affecting the activity of p-ERK1/2/RSPH3.
Zhang Z et al.·Hum Reprod
2023
Tumor size, stage and grade alterations of urinary peptidome in RCC.
Chinello C et al.·J Transl Med
2015
A Likelihood Approach for Uncovering Selective Sweep Signatures from Haplotype Data.
Harris AM et al.·Mol Biol Evol
2020
Burden of rare coding variants reveals genetic heterogeneity between obese and non-obese asthma patients in the African American population.
Liu Y et al.·Respir Res
2022Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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