TSPYL5

Chr 8

TSPY like 5

NCBI Gene: 85453 ENSG00000180543 UniProt: Q86VY4 OMIM: 614721

The protein binds chromatin and histones to regulate cell growth and DNA damage responses, particularly through modulation of the Akt signaling pathway and suppression of p53 protein levels. This highly constrained gene (pLI 0.85, LOEUF 0.45) has not yet been definitively associated with human disease, though its critical role in DNA damage response pathways suggests potential clinical relevance. Further research is needed to establish any disease associations and inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable chromatin binding activity and histone binding activity. Involved in several processes, including cellular response to gamma radiation; positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; and positive regulation of protein ubiquitination. Predicted to be active in chromatin and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.45

Clinical Summary— TSPYL5

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

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ClinVar Variants

58 VUS of 62 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.849

Z-score 2.73

OE 0.09 (0.03–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.22Z-score

OE missense 0.77 (0.69–0.88)

180 obs / 232.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.45)

0≤0.351.4

Missense OE?0.77 (0.69–0.88)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 1 / 10.6Missense obs/exp: 180 / 232.5Syn Z: -0.73

ClinVar Variant Classifications

62 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	58	0	58
Likely Benign	3	1	4
Benign	0	0	0
Total	61	1	62

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap TSPYL5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →