TPD52L2
Chr 20TPD52 like 2
Also known as: D54, TPD54
The protein is a member of the tumor protein D52-like family that forms homo- and heteromeric complexes through its N-terminal coiled-coil motif. Mutations in TPD52L2 cause neurodevelopmental disorder with intellectual disability, autism spectrum disorder, and dysmorphic facies, following an autosomal dominant inheritance pattern. This gene is highly constrained against loss-of-function variants (pLI near 1.0), suggesting intolerance to protein-disrupting mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
106 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 30 | 0 | 30 |
Likely Pathogenic | 0 | 0 | 8 | 0 | 8 |
VUS | 1 | 33 | 12 | 0 | 46 |
Likely Benign | 0 | 3 | 0 | 0 | 3 |
Benign | 0 | 1 | 0 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 1 | 37 | 50 | 0 | 89 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TPD52L2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools