HSPA1L

Chr 6

heat shock protein family A (Hsp70) member 1 like

Also known as: HSP70-1L, HSP70-HOM, HSP70T, hum70t

NCBI Gene: 3305ENSG00000204390UniProt: P34931

This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]

129
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HSPA1L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 99 VUS of 129 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.23LOEUF
pLI 0.000
Z-score 0.91
OE 0.75 (0.47–1.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.64Z-score
OE missense 0.90 (0.83–0.99)
325 obs / 359.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.75 (0.47–1.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.83–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 11 / 14.8Missense obs/exp: 325 / 359.2Syn Z: 0.73

ClinVar Variant Classifications

129 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS99
Likely Benign10
Benign12
Conflicting1
5
Pathogenic
2
Likely Pathogenic
99
VUS
10
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
1
93
5
0
99
Likely Benign
1
2
2
5
10
Benign
0
6
1
5
12
Conflicting
—1
Total21011510129

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

View in ClinVar →

Protein Context — Lollipop Plot

HSPA1L · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Validation and functional follow-up of cervical cancer risk variants at the HLA locus.
Eisenblätter R et al.·HLA
2024Natural history
Heat shock protein 70 genotypes HSPA1B and HSPA1L influence cytokine concentrations and interfere with outcome after major injury.
Schröder O et al.·Crit Care Med
2003
Association Studies of HSPA1A and HSPA1L Gene Polymorphisms With Schizophrenia.
Kowalczyk M et al.·Arch Med Res
2018
Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.
Zhang Y et al.·Front Immunol
2024
Polymorphisms of heat shock protein 70 gene (HSPA1A, HSPA1B and HSPA1L) and schizophrenia.
Pae CU et al.·Neurosci Res
2005
De novo and rare mutations in the HSPA1L heat shock gene associated with inflammatory bowel disease.
Takahashi S et al.·Genome Med
2017
Polymorphisms of heat shock protein-70 (HSPA1B and HSPA1L loci) do not influence infection or outcome risk in critically ill surgical patients.
Bowers DJ et al.·Shock
2006Cohort
Melatonin suppresses senescence-derived mitochondrial dysfunction in mesenchymal stem cells via the HSPA1L-mitophagy pathway.
Lee JH et al.·Aging Cell
2020
Prognostic Significance of the Hsp70 Gene Family in Colorectal Cancer.
Jiang W et al.·Med Sci Monit
2021
Functional diversity between HSP70 paralogs caused by variable interactions with specific co-chaperones.
Serlidaki D et al.·J Biol Chem
2020Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools