SPG21
Chr 15ARSPG21 abhydrolase domain containing, maspardin
Also known as: ABHD21, ACP33, BM-019, GL010, MAST
The protein binds to CD4 and modulates T cell activation by interacting with CD4's hydrophobic C-terminal amino acids through its noncatalytic alpha/beta hydrolase fold domain. Mutations cause autosomal recessive spastic paraplegia 21 (also known as Mast syndrome), which involves spasticity and neurodegeneration primarily affecting the lower extremities. This gene shows low constraint against loss-of-function variants (pLI 0.0007), consistent with its autosomal recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
ClinVar Variant Classifications
226 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 | 5 | 1 | 8 | 0 | 14 |
Likely Pathogenic | 7 | 0 | 3 | 0 | 10 |
VUS | 1 | 52 | 29 | 4 | 86 |
Likely Benign | 0 | 0 | 32 | 27 | 59 |
Benign | 0 | 0 | 25 | 0 | 25 |
Conflicting | — | 13 | |||
| Total | 13 | 53 | 97 | 31 | 207 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SPG21 · 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