TSPYL2

Chr X

TSPY like 2

Also known as: CDA1, CINAP, CTCL, DENTT, HRIHFB2216, NP79, SE204, TSPX

The protein functions in chromatin remodeling and nucleosome assembly as part of a transcriptional complex that responds to neuronal synaptic activity, and also inhibits cell cycle progression. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, reflecting its essential role in neuronal function.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOEUF 0.41
Clinical SummaryTSPYL2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
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ClinVar Variants
47 unique Pathogenic / Likely Pathogenic· 91 VUS of 200 total submissions
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GeneReview available — TSPYL2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.874
Z-score 3.18
OE 0.13 (0.050.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.33Z-score
OE missense 0.94 (0.851.05)
262 obs / 277.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.050.41)
00.351.4
Missense OE0.94 (0.851.05)
00.61.4
Synonymous OE1.39
01.21.6
LoF obs/exp: 2 / 15.5Missense obs/exp: 262 / 277.5Syn Z: -3.27

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic4
VUS91
Likely Benign10
Benign2
Conflicting1
43
Pathogenic
4
Likely Pathogenic
91
VUS
10
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
4
0
4
VUS
1
89
1
0
91
Likely Benign
0
6
1
3
10
Benign
0
1
1
0
2
Conflicting
1
Total196503151

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

View in ClinVar →

Protein Context — Lollipop Plot

TSPYL2 · 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

No active trials found for this gene.

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Clinical Literature
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