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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
8
Pubs (1 yr)
34
P/LP submissions
0%
P/LP missense
0.45
LOEUF
Mechanism
Clinical SummaryTSPYL5
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 57 VUS of 94 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.849
Z-score 2.73
OE 0.09 (0.030.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.22Z-score
OE missense 0.77 (0.690.88)
180 obs / 232.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.030.45)
00.351.4
Missense OE0.77 (0.690.88)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 1 / 10.6Missense obs/exp: 180 / 232.5Syn Z: -0.73

ClinVar Variant Classifications

94 submitted variants in ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic1
VUS57
Likely Benign3
33
Pathogenic
1
Likely Pathogenic
57
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
1
0
1
VUS
0
56
1
0
57
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total05835194

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

View in ClinVar →

Protein Context — Lollipop Plot

TSPYL5 · protein map & ClinVar variants

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

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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC