HSPA4L
Chr 4heat shock protein family A (Hsp70) member 4 like
Also known as: APG-1, APG1, HSPH3, Osp94
The protein functions as a molecular chaperone that prevents protein aggregation and protects cells from heat shock-induced damage. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
156 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 | 26 | 0 | 26 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 93 | 5 | 0 | 98 |
Likely Benign | 0 | 5 | 0 | 3 | 8 |
Benign | 0 | 0 | 0 | 2 | 2 |
| Total | 0 | 98 | 32 | 5 | 135 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HSPA4L · 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