HSPD1

Chr 2ARAD

heat shock protein family D (Hsp60) member 1

Also known as: CPN60, GROEL, HLD4, HSP-60, HSP60, HSP65, HuCHA60, SPG13

NCBI Gene: 3329ENSG00000144381UniProt: P10809OMIM: 118190

This mitochondrial chaperonin is essential for folding and assembly of newly imported proteins in the mitochondria. Mutations cause autosomal recessive spastic paraplegia 13 and hypomyelinating leukodystrophy 4, with some cases showing autosomal dominant inheritance. The pathogenicity results from impaired mitochondrial protein folding, which disrupts cellular energy metabolism and protein homeostasis.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.272 OMIM phenotypes
Clinical Summary— HSPD1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 165 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.993
Z-score 4.11
OE 0.09 (0.03–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.26Z-score
OE missense 0.64 (0.57–0.72)
195 obs / 306.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.03–0.27)
0≤0.351.4
Missense OE0.64 (0.57–0.72)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 2 / 23.5Missense obs/exp: 195 / 306.1Syn Z: -0.01

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic4
VUS165
Likely Benign89
Benign12
Conflicting2
14
Pathogenic
4
Likely Pathogenic
165
VUS
89
Likely Benign
12
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
4
0
0
4
VUS
5
140
15
5
165
Likely Benign
0
1
50
38
89
Benign
0
0
12
0
12
Conflicting
—2
Total51459143286

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HSPD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients