SPAG1

Chr 8AR

sperm associated antigen 1

Also known as: CILD28, CT140, DNAAF13, HEL-S-268, HSD-3.8, SP75, TPIS

SPAG1 encodes a GTPase that binds GTP and is involved in cytoplasmic assembly of ciliary dynein arms, with additional roles in spermatogenesis and fertilization. Mutations cause primary ciliary dyskinesia type 28, inherited in an autosomal recessive pattern. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.761 OMIM phenotype
Clinical SummarySPAG1
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Gene-Disease Validity (ClinGen)
primary ciliary dyskinesia 28 · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.000
Z-score 2.75
OE 0.53 (0.370.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.91Z-score
OE missense 0.88 (0.810.95)
376 obs / 428.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.370.76)
00.351.4
Missense OE0.88 (0.810.95)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 21 / 39.7Missense obs/exp: 376 / 428.9Syn Z: 2.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSPAG1-related primary ciliary dyskinesia associated with defective outer and inner dynein armsLOFAR

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

DN
0.7229th %ile
GOF
0.6736th %ile
LOF
0.2189th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SPAG1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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