RSPH1

Chr 21AR

radial spoke head component 1

Also known as: CT79, RSP44, RSPH10A, TSA2, TSGA2

This gene encodes a protein that functions as part of axonemal radial spoke complexes essential for sperm and ciliary motility. Mutations cause primary ciliary dyskinesia-24, inherited in an autosomal recessive pattern. The gene is expressed in tissues with motile cilia or flagella including the respiratory tract and testes.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 24MIM #615481
AR
0
Active trials
8
Pubs (1 yr)
155
P/LP submissions
4%
P/LP missense
0.98
LOEUF
LOF
Mechanism· G2P
Clinical SummaryRSPH1
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Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 24 · 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
113 unique Pathogenic / Likely Pathogenic· 114 VUS of 420 total submissions
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GeneReview available — RSPH1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.61
OE 0.61 (0.390.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.14Z-score
OE missense 0.97 (0.861.10)
186 obs / 191.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.390.98)
00.351.4
Missense OE0.97 (0.861.10)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 12 / 19.7Missense obs/exp: 186 / 191.4Syn Z: -0.25
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRSPH1-related primary ciliary dyskinesia with central-complex and radial-spoke defectsLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.74top 25%
GOF
0.6344th %ile
LOF
0.2873th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

420 submitted variants in ClinVar

Classification Summary

Pathogenic101
Likely Pathogenic12
VUS114
Likely Benign133
Benign36
Conflicting8
101
Pathogenic
12
Likely Pathogenic
114
VUS
133
Likely Benign
36
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
3
89
0
101
Likely Pathogenic
4
1
7
0
12
VUS
1
90
20
3
114
Likely Benign
1
8
61
63
133
Benign
0
1
29
6
36
Conflicting
8
Total1510320672404

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

View in ClinVar →

Protein Context — Lollipop Plot

RSPH1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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