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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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HSPA4L
heat shock protein family A (Hsp70) member 4 like
Chromosome 4 · 4q28.1
NCBI Gene: 22824Ensembl: ENSG00000164070.12HGNC: HGNC:17041UniProt: A0A140VKE7
158PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolATP bindingprotein foldingresponse to unfolded proteinnasopharyngeal carcinomaopen-angle glaucomaMale infertility with spermatogenesis disorder due to single gene mutationcorneal ulcer
✦AI Summary

HSPA4L (heat shock protein family A member 4 like) is a molecular chaperone belonging to the HSP110 family that functions primarily in protein folding and prevention of protein aggregation 1. The protein possesses adenyl-nucleotide exchange factor activity and localizes to the cytoplasm, cytosol, and nucleus, where it exhibits ATP-binding capacity 2. HSPA4L is expressed ubiquitously with predominant expression in testis and enriched in spermatogenic cells 3. It collaborates with its homolog HSPA4 as a cochaperone essential for embryonic lung maturation and proper surfactant protein expression 2. Functionally, HSPA4L is critical for normal spermatogenesis; Hspa4l-deficient mice show reduced sperm motility and count due to increased germ cell apoptosis, with approximately 42% of male knockouts exhibiting infertility 3. Additionally, HSPA4L plays a role in osmotolerance, as null mutants display preferential susceptibility to osmotic stress 3. In disease contexts, HSPA4L is downregulated in asthenospermia through miR-429-mediated suppression, correlating with reduced sperm motility and viability 1. HSPA4L is overexpressed in leukemia cells and provokes humoral immune responses in leukemia patients, suggesting potential immunotherapeutic targeting 4. In nasopharyngeal carcinoma, HSPA4L overexpression is suppressed by the tumor suppressor miR-497, indicating oncogenic function 5.

Sources cited
1
HSPA4L is downregulated in asthenospermia via miR-429-mediated suppression and correlates with reduced sperm motility and viability
PMID: 28598115
2
HSPA4L and HSPA4 collaborate as cochaperones in embryonic lung maturation, with double mutants showing impaired chaperone activity and pulmonary hypoplasia
PMID: 23980576
3
HSPA4L is predominantly expressed in testis and spermatogenic cells; Hspa4l-deficient mice show 42% male infertility, reduced sperm motility due to germ cell apoptosis, and increased osmotic stress susceptibility
PMID: 16923965
4
HSPA4L is overexpressed in leukemia cells and elicits humoral immune responses in leukemia patients, potentially serving as an antigen for immunotherapy
PMID: 17588478
5
HSPA4L is overexpressed in nasopharyngeal carcinoma and suppressed by tumor suppressor miR-497, promoting cancer phenotypes
PMID: 26486082
Disease Associationsⓘ20
nasopharyngeal carcinomaOpen Targets
0.06Suggestive
open-angle glaucomaOpen Targets
0.05Suggestive
Male infertility with spermatogenesis disorder due to single gene mutationOpen Targets
0.05Suggestive
corneal ulcerOpen Targets
0.05Suggestive
azoospermiaOpen Targets
0.05Suggestive
alcohol drinkingOpen Targets
0.04Suggestive
familial juvenile hyperuricemic nephropathy type 1Open Targets
0.04Suggestive
spermatogenic failure 65Open Targets
0.04Suggestive
spermatogenic failure 84Open Targets
0.04Suggestive
spermatogenic failure 93Open Targets
0.04Suggestive
ring chromosome YOpen Targets
0.04Suggestive
spermatogenic failure 56Open Targets
0.04Suggestive
spermatogenic failure 92Open Targets
0.04Suggestive
spermatogenic failure 94Open Targets
0.04Suggestive
spermatogenic failure 54Open Targets
0.04Suggestive
spermatogenic failure 51Open Targets
0.04Suggestive
congenital bilateral absence of vas deferensOpen Targets
0.04Suggestive
spermatogenic failure, X-linked, 3Open Targets
0.03Suggestive
spermatogenic failure 39Open Targets
0.03Suggestive
spermatogenic failure 58Open Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DNAJC4Shared pathway100%DNAJB5Shared pathway100%GRPEL1Protein interaction100%HSPA9Protein interaction97%CLPBProtein interaction97%HSPBP1Protein interaction95%
Tissue Expression6 tissues
Brain
100%
Heart
97%
Liver
75%
Bone Marrow
52%
Ovary
40%
Lung
12%
Gene Interaction Network
Click a node to explore
HSPA4LDNAJC4DNAJB5GRPEL1HSPA9CLPBHSPBP1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O95757
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.55Moderately Constrained
pLIⓘ
0.75Intermediate
Observed/Expected LoF0.38 [0.27–0.55]
RankingsWhere HSPA4L stands among ~20K protein-coding genes
  • #2,846of 20,598
    Most Researched158 · top quartile
  • #3,468of 17,882
    Most Constrained (LOEUF)0.55 · top quartile
Genes detectedHSPA4L
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
[Expression of
PMID: 28598115
Sichuan Da Xue Xue Bao Yi Xue Ban · 2016
1.00
2
Respiratory distress and early neonatal lethality in Hspa4l/Hspa4 double-mutant mice.
PMID: 23980576
Am J Respir Cell Mol Biol · 2014
0.90
3
Hspa4l-deficient mice display increased incidence of male infertility and hydronephrosis development.
PMID: 16923965
Mol Cell Biol · 2006
0.80
4
Heat shock protein A4L is a potent autoantigen for testicular autoimmunity in mice.
PMID: 33894646
J Reprod Immunol · 2021
0.76
5
Mammalian heat shock protein A4 family ortholog Hsc70Cb is required for two phases of spermatogenesis in D. melanogaster.
PMID: 39991973
Reproduction · 2025
0.70