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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
HSPD1
heat shock protein family D (Hsp60) member 1
Chromosome 2 Β· 2q33.1
NCBI Gene: 3329Ensembl: ENSG00000144381.19HGNC: HGNC:5261UniProt: A0A024R3X4
739PubMed Papers
22Diseases
0Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
apolipoprotein A-I bindingpositive regulation of type II interferon productionT cell activationlipopolysaccharide bindinghypomyelinating leukodystrophy 4Autosomal dominant spastic paraplegia type 13Pelizaeus-Merzbacher-like disease due to HSPD1 mutationhereditary spastic paraplegia 13
✦AI Summary

HSPD1 encodes a mitochondrial chaperonin that plays essential roles in protein folding and cellular metabolism. The protein forms heptameric rings that work with Hsp10 to facilitate correct folding of imported mitochondrial proteins and prevent misfolding under stress conditions 1. HSPD1 functions through ATP-dependent cycles where substrate proteins are sequestered within the chaperonin cavity for proper folding 1. Beyond its classical chaperone function, HSPD1 stabilizes ATP5A1, a key component of mitochondrial ATP synthase, by reducing its K48-linked ubiquitination and degradation, thereby activating AKT/mTOR signaling pathways 2. The protein also binds to and regulates repair of deoxyinosine in DNA, contributing to mitochondrial DNA damage control 3. HSPD1 is highly expressed in various cancers including osteosarcoma and non-small cell lung cancer, where it promotes tumor progression, metastasis, and epithelial-mesenchymal transition 24. High HSPD1 expression correlates with poor prognosis in cancer patients, and its inhibition severely impairs oxidative phosphorylation and suppresses cancer cell proliferation 4. These findings establish HSPD1 as both a critical metabolic regulator and potential therapeutic target in cancer treatment.

Sources cited
1
HSPD1 is a mitochondrial protein involved in ATP-dependent protein folding cycles
PMID: 34817906
2
HSPD1 stabilizes ATP5A1 and activates AKT/mTOR signaling in osteosarcoma
PMID: 39430254
3
HSPD1 binds to deoxyinosine-containing DNA and regulates DNA damage response
PMID: 36852893
4
HSPD1 is highly expressed in NSCLC, correlates with poor prognosis, and its inhibition impairs oxidative phosphorylation
PMID: 34364401
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜22
hypomyelinating leukodystrophy 4Open Targets
0.77Strong
Autosomal dominant spastic paraplegia type 13Open Targets
0.75Strong
Pelizaeus-Merzbacher-like disease due to HSPD1 mutationOpen Targets
0.74Strong
hereditary spastic paraplegia 13Open Targets
0.68Moderate
neurodegenerative diseaseOpen Targets
0.56Moderate
leukodystrophyOpen Targets
0.46Moderate
atrial fibrillationOpen Targets
0.33Weak
schizophreniaOpen Targets
0.20Weak
Spastic paraplegiaOpen Targets
0.20Weak
hereditary spastic paraplegiaOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
bipolar disorderOpen Targets
0.19Weak
carcinoma of gallbladder and extrahepatic biliary tractOpen Targets
0.16Weak
cervical carcinomaOpen Targets
0.15Weak
autosomal dominant complex spastic paraplegiaOpen Targets
0.15Weak
allergic rhinitisOpen Targets
0.14Weak
major depressive disorderOpen Targets
0.14Weak
deep vein thrombosisOpen Targets
0.12Weak
Intellectual disabilityOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
Leukodystrophy, hypomyelinating, 4UniProt
Spastic paraplegia 13, autosomal dominantUniProt
Pathogenic Variants8
NM_002156.5(HSPD1):c.86A>G (p.Asp29Gly)Pathogenic
Hypomyelinating leukodystrophy 4|Leukodystrophy
β˜…β˜†β˜†β˜†2025β†’ Residue 29
NM_002156.5(HSPD1):c.185T>C (p.Val62Ala)Likely pathogenic
Hypomyelinating leukodystrophy 4
β˜…β˜†β˜†β˜†2024β†’ Residue 62
NM_002156.5(HSPD1):c.188T>C (p.Ile63Thr)Likely pathogenic
HSPD1-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 63
NM_002156.5(HSPD1):c.329G>T (p.Gly110Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 110
NM_002156.5(HSPD1):c.397A>G (p.Lys133Glu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2014β†’ Residue 133
NM_002156.5(HSPD1):c.292G>A (p.Val98Ile)Pathogenic
Hereditary spastic paraplegia 13
β˜…β˜†β˜†β˜†β†’ Residue 98
NM_002156.5(HSPD1):c.139T>G (p.Leu47Val)Likely pathogenic
Hypomyelinating leukodystrophy 4
β˜†β˜†β˜†β˜†2020β†’ Residue 47
NM_002156.5(HSPD1):c.1381C>G (p.Gln461Glu)Pathogenic
Hereditary spastic paraplegia 13
β˜†β˜†β˜†β˜†2018β†’ Residue 461
View on ClinVar β†—
Related Genes
CCT6AProtein interaction100%HSPA1BProtein interaction100%CSProtein interaction100%TLR4Protein interaction100%STIP1Protein interaction100%PRNPProtein interaction100%
Tissue Expression6 tissues
Liver
100%
Ovary
36%
Brain
34%
Bone Marrow
32%
Heart
30%
Lung
27%
Gene Interaction Network
Click a node to explore
HSPD1CCT6AHSPA1BCSTLR4STIP1PRNP
PROTEIN STRUCTURE
Preparing viewer…
PDB9ES2 Β· 2.44 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.18Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.06 [0.02–0.18]
RankingsWhere HSPD1 stands among ~20K protein-coding genes
  • #282of 20,598
    Most Researched739 Β· top 5%
  • #3,013of 5,498
    Most Pathogenic Variants8
  • #366of 17,882
    Most Constrained (LOEUF)0.18 Β· top 5%
Genes detectedHSPD1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Mitochondrial Stress Response and Cancer.
PMID: 32451306
Trends Cancer Β· 2020
1.00
2
PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis.
PMID: 31177901
Autophagy Β· 2020
0.90
3
Artificial targeting of autophagy components to mitochondria reveals both conventional and unconventional mitophagy pathways.
PMID: 39177530
Autophagy Β· 2025
0.84
4
[Not Available].
PMID: 28803683
Presse Med Β· 2017
0.82
5
Integrating single-cell sequencing and machine learning to uncover the role of mitophagy in subtyping and prognosis of esophageal cancer.
PMID: 39948301
Apoptosis Β· 2025
0.80