SPATA2
Chr 20spermatogenesis associated 2
Also known as: PD1, PPP1R145, tamo
SPATA2 encodes a bridging factor that recruits the deubiquitinase CYLD to the LUBAC complex, thereby regulating TNF-induced necroptosis and controlling RIPK1 kinase activity. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.29), suggesting mutations would likely cause severe disease, though no specific pediatric neurogenetic disorders have been definitively associated with SPATA2 mutations to date. Given its role in cell death pathways and high constraint metrics, pathogenic variants would be expected to follow an autosomal dominant inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
104 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 | 7 | 0 | 7 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 85 | 3 | 0 | 88 |
Likely Benign | 0 | 3 | 0 | 1 | 4 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 88 | 12 | 1 | 101 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SPATA2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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