TSPY1

Chr Y

testis specific protein Y-linked 1

Also known as: CT78, DYS14, TSPY, pJA923

NCBI Gene: 7258 ENSG00000258992 UniProt: Q01534 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is found only in testicular tissue and may be involved in spermatogenesis. Many functional paralogs and pseudogenes of this gene are present in a cluster in humans, but only a single, nonfunctional orthologous gene is found in mouse. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.87

Clinical Summary— TSPY1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

1 total variants — no pathogenic classifications of 1 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 OE?0.00 (0.00–1.87)

0≤0.351.4

Missense OE?0.84 (0.37–1.79)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 0 / 0.3Missense obs/exp: 3 / 3.6Syn Z: 0.13

This gene — mechanism propensity

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

1 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign1

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Synonymous	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	0	0
Likely Benign	1	1
Benign	0	0
Total	1	1

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

View in ClinVar →

52 pathogenic / likely-pathogenic (of 62) ClinVar copy-number / structural variants overlap TSPY1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →