SPA17

Chr 11

sperm autoantigenic protein 17

Also known as: CT22, SP17, SP17-1

NCBI Gene: 53340ENSG00000064199UniProt: Q15506

SPA17 encodes a sperm surface protein that binds to the zona pellucida of oocytes and functions in cell-cell adhesion through its carbohydrate binding motifs and calmodulin-binding domain. Mutations in SPA17 cause male infertility due to defective sperm-egg binding. The gene shows autosomal recessive inheritance and is not highly constrained against loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
60
P/LP submissions
0%
P/LP missense
1.40
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SPA17
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 26 VUS of 95 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.40LOEUF
pLI 0.007
Z-score 0.90
OE 0.62 (0.30–1.40)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.16Z-score
OE missense 1.05 (0.88–1.25)
86 obs / 82.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.62 (0.30–1.40)
0≤0.351.4
Missense OE1.05 (0.88–1.25)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 4 / 6.5Missense obs/exp: 86 / 82.0Syn Z: -0.14
DN
0.84top 10%
GOF
0.80top 10%
LOF
0.1399th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic2
VUS26
Likely Benign1
58
Pathogenic
2
Likely Pathogenic
26
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
58
0
58
Likely Pathogenic
0
0
2
0
2
VUS
0
20
6
0
26
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total02166087

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

View in ClinVar →

Protein Context — Lollipop Plot

SPA17 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Quantitative phosphoproteomics analyses reveal the regulatory mechanisms related to frozen-thawed sperm capacitation and acrosome reaction in yak (Bos grunniens)
Zhang R et al.·Front Physiol
2022Functional
Sperm protein antigen 17 and Sperm flagellar 1 cancer testis antigens are expressed in a rare case of ciliated foregut cyst of the common hepatic duct.
Grizzi F et al.·Pathol Res Pract
2023
Immunological Features and Potential Biomarkers of Systemic Sclerosis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis
Shao S et al.·Clin Respir J
2025
Beyond PKA: Evolutionary and structural insights that define a docking and dimerization domain superfamily
Dahlin HR et al.·J Biol Chem
2021
Decreased AKAP4/PKA signaling pathway in high DFI sperm affects sperm capacitation
Zhang K et al.·Asian J Androl
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients