HSPH1
Chr 13heat shock protein family H (Hsp110) member 1
Also known as: HSP105, HSP105A, HSP105B, NY-CO-25
The protein functions as a nucleotide exchange factor for heat shock protein 70 family chaperones and acts as a holdase that prevents aggregation of misfolded proteins under cellular stress conditions. Mutations cause neurodevelopmental disorder with spastic diplegia and visual defects, typically presenting in early childhood with developmental delays, spasticity affecting the legs, and ophthalmologic abnormalities. The gene is highly constrained against loss-of-function variants and inheritance follows an autosomal dominant pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
ClinVar Variant Classifications
174 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 | 37 | 0 | 37 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 80 | 7 | 0 | 87 |
Likely Benign | 0 | 6 | 2 | 3 | 11 |
Benign | 0 | 1 | 1 | 1 | 3 |
| Total | 0 | 87 | 47 | 4 | 138 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
HSPH1 · 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