TSPY1

Chr Y

testis specific protein Y-linked 1

Also known as: CT78, DYS14, TSPY, pJA923

NCBI Gene: 7258ENSG00000258992UniProt: Q01534OMIM: 480100

The protein encoded by TSPY1 is expressed exclusively in testicular tissue and is involved in sperm differentiation and proliferation during spermatogenesis. This gene has low constraint against loss-of-function variants (LOEUF 1.87), and no established disease associations have been reported in the provided data. TSPY1 exists as part of a multi-copy gene cluster with many functional paralogs, which may provide functional redundancy.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.87
Clinical Summary— TSPY1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 5 VUS of 63 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.87LOEUF
pLI 0.310
Z-score 0.48
OE 0.00 (0.00–1.87)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.10Z-score
OE missense 0.84 (0.37–1.79)
3 obs / 3.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–1.87)
0≤0.351.4
Missense OE0.84 (0.37–1.79)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 0 / 0.3Missense obs/exp: 3 / 3.6Syn Z: 0.13
DN
0.6163th %ile
GOF
0.74top 25%
LOF
0.2190th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

63 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic2
VUS5
Likely Benign5
50
Pathogenic
2
Likely Pathogenic
5
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————50
Likely Pathogenic
————2
VUS
————5
Likely Benign
————5
Benign
————0
Total—62

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TSPY1 · 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
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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