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HSPA14

gene
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Also known as HSP70-4HSP70L1

Summary

HSPA14 (heat shock protein family A (Hsp70) member 14, HGNC:29526) is a protein-coding gene on chromosome 10p13, encoding Heat shock 70 kDa protein 14 (Q0VDF9). Component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. It is a selective cancer dependency (DepMap: 34.9% of cell lines).

Predicted to enable ATP hydrolysis activity; heat shock protein binding activity; and protein folding chaperone. Predicted to be involved in chaperone cofactor-dependent protein refolding and protein refolding. Located in cytosol and ribosome.

Source: NCBI Gene 51182 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 73 total
  • Druggable target: yes
  • Cancer dependency (DepMap): dependent in 34.9% of screened cell lines
  • MANE Select transcript: NM_016299

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29526
Approved symbolHSPA14
Nameheat shock protein family A (Hsp70) member 14
Location10p13
Locus typegene with protein product
StatusApproved
AliasesHSP70-4, HSP70L1
Ensembl geneENSG00000187522
Ensembl biotypeprotein_coding
OMIM610369
Entrez51182

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000378372, ENST00000441647, ENST00000470430

RefSeq mRNA: 1 — MANE Select: NM_016299 NM_016299

CCDS: CCDS7103

Canonical transcript exons

ENST00000378372 — 14 exons

ExonStartEnd
ENSE000006916511484860914848657
ENSE000006916561484879014848895
ENSE000006916741486708314867295
ENSE000006916781486773614867909
ENSE000010984421487059714870667
ENSE000010984441485412514854280
ENSE000010984461485584114855943
ENSE000014772601487152814871741
ENSE000019536061483830614838459
ENSE000033944631484972114849811
ENSE000034158521485121914851323
ENSE000035435881483990514839985
ENSE000035581941485237014852531
ENSE000035976221484007514840157

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.0563 / max 221.5980, expressed in 1814 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
10398120.48231813
1039824.62811584
1039771.0226572
1039780.6718336
1039790.251492

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
secondary oocyteCL:000065597.26gold quality
oocyteCL:000002395.79gold quality
tongue squamous epitheliumUBERON:000691991.09gold quality
middle temporal gyrusUBERON:000277189.63gold quality
right testisUBERON:000453489.28gold quality
rectumUBERON:000105289.23gold quality
deltoidUBERON:000147689.01gold quality
left testisUBERON:000453389.00gold quality
gastrocnemiusUBERON:000138888.84gold quality
cervix squamous epitheliumUBERON:000692288.57gold quality
muscle of legUBERON:000138388.49gold quality
testisUBERON:000047388.43gold quality
mucosa of sigmoid colonUBERON:000499388.43gold quality
muscle organUBERON:000163088.21gold quality
squamous epitheliumUBERON:000691488.13gold quality
vastus lateralisUBERON:000137988.04gold quality
quadriceps femorisUBERON:000137787.92gold quality
esophagus squamous epitheliumUBERON:000692087.90gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450287.85gold quality
Brodmann (1909) area 23UBERON:001355487.69gold quality
colonic mucosaUBERON:000031787.63gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099187.54gold quality
biceps brachiiUBERON:000150787.45gold quality
cerebellar hemisphereUBERON:000224587.39gold quality
cerebellar cortexUBERON:000212987.32gold quality
hair follicleUBERON:000207387.21gold quality
cerebellar vermisUBERON:000472087.09gold quality
gingival epitheliumUBERON:000194987.07gold quality
right hemisphere of cerebellumUBERON:001489087.07gold quality
monocyteCL:000057687.06gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes5.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting HSPA14, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-LET-7A-3P100.0074.033932
HSA-LET-7B-3P100.0074.083913
HSA-LET-7F-1-3P100.0074.023928
HSA-MIR-98-3P100.0074.083907
HSA-MIR-4789-5P99.9870.762721
HSA-LET-7F-2-3P99.9870.982588
HSA-MIR-1185-1-3P99.9871.042593
HSA-MIR-1185-2-3P99.9871.042593
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-374C-5P99.8072.062910
HSA-MIR-655-3P99.8072.192909
HSA-MIR-409-3P99.5066.331192
HSA-MIR-582-5P99.4770.792635
HSA-MIR-57899.4668.361787
HSA-MIR-6853-3P99.3670.791558
HSA-MIR-1912-5P97.9467.98832

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

  • results demonstrate that Hsp70L1 has enhanced Th1 polarizing and adjuvant properties, which appear to be mediated via activation of dendritic cells (PMID:14592822)
  • a novel pathway (NBS1-HSF4b-HSPA4/HSPA14 axis) to induce migration, invasion, and transformation, suggesting the activation of multiple signaling events induced by NBS1 overexpression (PMID:21208456)
  • TLR4 is a key receptor mediating the interaction of Hsp70L1 with DCs and subsequently enhancing the induction of Th1 immune response by Hsp70L1/antigen fusion protein (PMID:21730052)
  • Intracellular HSP70L1 inhibits human dendritic cell maturation by promoting suppressive H3K27me3 and H2AK119Ub1 histone modifications. (PMID:30635648)
  • HSP70L1 expression is induced by TERT.TERT promotes formation of a telomere protective complex containing Hsp70L1. (PMID:31616780)
  • Expression of HSPA14 in patients with acute HIV-1 infection and its effect on HIV-1 replication. (PMID:36845091)

Cross-species orthologs

7 orthologs

OrganismSymbolGene ID
danio_reriohspa14ENSDARG00000058030
mus_musculusHspa14ENSMUSG00000109865
rattus_norvegicusHspa14ENSRNOG00000015212
drosophila_melanogasterCG7182FBGN0035878
caenorhabditis_eleganshsp-70WBGENE00002026
caenorhabditis_elegansWBGENE00009691
caenorhabditis_elegansWBGENE00009692

Paralogs (13): HSPA5 (ENSG00000044574), HSPA8 (ENSG00000109971), HSPA9 (ENSG00000113013), HSPH1 (ENSG00000120694), HSPA2 (ENSG00000126803), HYOU1 (ENSG00000149428), HSPA13 (ENSG00000155304), HSPA4L (ENSG00000164070), HSPA4 (ENSG00000170606), HSPA6 (ENSG00000173110), HSPA1B (ENSG00000204388), HSPA1A (ENSG00000204389), HSPA1L (ENSG00000204390)

Protein

Protein identifiers

Heat shock 70 kDa protein 14 — Q0VDF9 (reviewed: Q0VDF9)

Alternative names: HSP70-like protein 1, Heat shock protein HSP60, Heat shock protein family A member 14

All UniProt accessions (2): Q0VDF9, H7C2A1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, binds to the nascent polypeptide chain, while DNAJC2 stimulates its ATPase activity.

Subunit / interactions. Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2.

Subcellular location. Cytoplasm. Cytosol.

Miscellaneous. Acts as a potent immunoadjuvant, capable to interact with antigen-presenting cells and generating efficient CD8(+) T-cell responses. May be used as adjuvant to enhance effect of vaccine G1F/M2, a candidate vaccine against respiratory syncytial virus (RSV), a major respiratory pathogen in newborns. May also be used as adjuvant to prepare antigenic fusion protein for the therapeutics of cancers.

Similarity. Belongs to the heat shock protein 70 family.

RefSeq proteins (1): NP_057383* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR013126Hsp_70_famFamily
IPR018181Heat_shock_70_CSConserved_site
IPR029047HSP70_peptide-bd_sfHomologous_superfamily
IPR042049HSPA14_NBDDomain
IPR043129ATPase_NBDHomologous_superfamily

Pfam: PF00012

UniProt features (7 total): sequence conflict 5, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q0VDF9-F191.500.78

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-3371453Regulation of HSF1-mediated heat shock response

MSigDB gene sets: 152 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, YANG_BREAST_CANCER_ESR1_LASER_DN, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, WEI_MYCN_TARGETS_WITH_E_BOX, MUELLER_PLURINET, CAGCAGG_MIR370, GOBP_PROTEIN_MATURATION, chr10p13, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GATA1_01, GNF2_FBL, GOBP_PROTEIN_FOLDING, DODD_NASOPHARYNGEAL_CARCINOMA_UP, TIEN_INTESTINE_PROBIOTICS_24HR_UP

GO Biological Process (3): protein refolding (GO:0042026), ‘de novo’ cotranslational protein folding (GO:0051083), protein folding (GO:0006457)

GO Molecular Function (7): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), heat shock protein binding (GO:0031072), protein folding chaperone (GO:0044183), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), ribosome (GO:0005840)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Cellular response to heat stress1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
protein folding2
ATP-dependent activity2
‘de novo’ protein folding1
cellular process1
protein maturation1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
ribonucleoside triphosphate phosphatase activity1
protein binding1
molecular_function1
protein folding chaperone1
nucleoside phosphate binding1
heterocyclic compound binding1
binding1
intracellular membrane-bounded organelle1
intracellular anatomical structure1
cytoplasm1
membrane1
cell periphery1
intracellular membraneless organelle1

Protein interactions and networks

STRING

4298 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HSPA14DNAJC2Q99543982
HSPA14DNAJB4Q9UDY4742
HSPA14TXNDC9O14530678
HSPA14HSP90AB1P08238667
HSPA14PGM1P36871664
HSPA14HSPA12AO43301657
HSPA14HSPA12BQ96MM6624
HSPA14HSPE1P61604541
HSPA14DNAJB1P25685506
HSPA14HSPA4P34932503
HSPA14HSPD1P10809503
HSPA14HSP90AA1P07900482
HSPA14TNFP01375432
HSPA14HLA-EP13747423
HSPA14DNAJA1P31689420

IntAct

65 interactions, top by confidence:

ABTypeScore
RELL2OXSR1psi-mi:“MI:0914”(association)0.830
WRAP53TCP1psi-mi:“MI:0914”(association)0.690
DNAJC2HSPA14psi-mi:“MI:0915”(physical association)0.670
HSPA14DNAJC2psi-mi:“MI:0914”(association)0.670
GPX7GAKpsi-mi:“MI:0914”(association)0.640
NFAM1HSPA14psi-mi:“MI:0915”(physical association)0.590
HSCBHSPA14psi-mi:“MI:0915”(physical association)0.550
SNRNP27UBA6psi-mi:“MI:0914”(association)0.530
DEFA5NUDT19psi-mi:“MI:0914”(association)0.530
XAGE1ATHAP12psi-mi:“MI:0914”(association)0.530
POLR3HPOLR3Apsi-mi:“MI:0914”(association)0.530
HSPA14psi-mi:“MI:0915”(physical association)0.490
DNAJC2HSPA14psi-mi:“MI:0915”(physical association)0.400
HSPA14NUDT14psi-mi:“MI:0915”(physical association)0.400
HSPA14htpGpsi-mi:“MI:0915”(physical association)0.370
HSPA14psi-mi:“MI:0915”(physical association)0.370
HSPA14CFTRpsi-mi:“MI:0915”(physical association)0.370
HSPA14GCNT1psi-mi:“MI:0915”(physical association)0.370
Septin9SEPTIN8psi-mi:“MI:0914”(association)0.350

BioGRID (121): HSPA14 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), HSPA14 (Co-fractionation), HSPA14 (Co-fractionation), HSPA14 (Co-fractionation), HSPA14 (Co-fractionation), HSPA14 (Co-fractionation), HSPA14 (Synthetic Lethality), HSPA14 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS)

ESM2 similar proteins: A2VD93, A5D8N7, E1C2P3, G0SCU5, G4NAY4, O65719, P02827, P09189, P0CB32, P11143, P11144, P11484, P16019, P22774, P24629, P26413, P26791, P27322, P29357, P37899, P39987, P40150, P41770, P55063, P87222, Q05746, Q05944, Q0VDF9, Q10284, Q2YDD0, Q4R6J2, Q54MR6, Q557E0, Q5FVX7, Q5RE21, Q5RGE6, Q5ZM98, Q6AYB4, Q6CQ83, Q707W3

Diamond homologs: A2Q0Z1, A2VD93, A5A8V7, A5D8N7, E1C2P3, F5HB71, J9VZ70, O59855, O73885, P02827, P08106, P08418, P09189, P09435, P09446, P0CB32, P0DMV8, P0DMV9, P0DMW0, P0DMW1, P10591, P10592, P11021, P11142, P11146, P11147, P14659, P16019, P16474, P16627, P17066, P17156, P17879, P18694, P19120, P19378, P20163, P22010, P22202, P25840

SIGNOR signaling

1 interactions.

AEffectBMechanism
HSPA14“form complex”“Ribosome-associated complex”binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

73 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance49
Likely benign3
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2824 predictions. Top by Δscore:

VariantEffectΔscore
10:14839899:CTCTA:Cacceptor_loss1.0000
10:14839900:TCTA:Tacceptor_loss1.0000
10:14839901:CTAG:Cacceptor_loss1.0000
10:14839902:TAGGA:Tacceptor_loss1.0000
10:14839903:A:AGacceptor_gain1.0000
10:14839903:A:ATacceptor_loss1.0000
10:14839903:AG:Aacceptor_gain1.0000
10:14839903:AGGAT:Aacceptor_gain1.0000
10:14839904:G:GGacceptor_gain1.0000
10:14839904:GG:Gacceptor_gain1.0000
10:14839904:GGA:Gacceptor_gain1.0000
10:14839904:GGAT:Gacceptor_gain1.0000
10:14839904:GGATG:Gacceptor_gain1.0000
10:14839983:G:GTdonor_gain1.0000
10:14839983:GAG:Gdonor_gain1.0000
10:14839983:GAGG:Gdonor_loss1.0000
10:14839984:AGGTA:Adonor_loss1.0000
10:14839986:G:GGdonor_gain1.0000
10:14839986:GTACT:Gdonor_loss1.0000
10:14839987:T:Adonor_loss1.0000
10:14840073:A:AGacceptor_gain1.0000
10:14840074:G:GGacceptor_gain1.0000
10:14840074:GATT:Gacceptor_gain1.0000
10:14840154:GAAG:Gdonor_gain1.0000
10:14840155:AAGG:Adonor_loss1.0000
10:14840156:AG:Adonor_loss1.0000
10:14840157:GG:Gdonor_loss1.0000
10:14840158:G:GCdonor_loss1.0000
10:14840159:T:Adonor_loss1.0000
10:14848601:AT:Aacceptor_gain1.0000

AlphaMissense

3302 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
10:14867203:G:CA372P0.997
10:14867212:G:CA375P0.997
10:14854172:T:CL261S0.996
10:14854197:A:CK269N0.996
10:14854197:A:TK269N0.996
10:14867198:G:AG370D0.996
10:14849763:T:AV140D0.995
10:14854183:G:CA265P0.995
10:14854184:C:AA265D0.995
10:14867087:T:AV333D0.995
10:14867200:G:CA371P0.995
10:14867204:C:AA372D0.995
10:14838416:G:AG5E0.994
10:14838448:G:CA16P0.994
10:14839963:T:AV39D0.994
10:14838449:C:AA16D0.993
10:14851227:C:AA159D0.993
10:14852513:T:CL239P0.993
10:14839931:T:AN28K0.992
10:14839931:T:GN28K0.992
10:14854205:T:CL272S0.992
10:14851278:C:AA176D0.991
10:14852515:G:CA240P0.991
10:14854170:A:CK260N0.991
10:14854170:A:TK260N0.991
10:14871550:T:CC492R0.991
10:14838415:G:AG5R0.990
10:14838415:G:CG5R0.990
10:14840081:G:AG49R0.990
10:14840081:G:CG49R0.990

dbSNP variants (sampled 300 via entrez): RS1000088516 (10:14861966 C>G), RS1000177458 (10:14843139 G>T), RS1000193734 (10:14867630 T>A,C), RS1000309553 (10:14837637 G>A), RS1000446208 (10:14860265 C>G,T), RS1000453218 (10:14865951 A>G), RS1000527611 (10:14866277 C>A,G,T), RS1000613070 (10:14843419 G>A,C), RS1000672799 (10:14849481 G>A), RS1000869763 (10:14839536 A>C), RS1000942756 (10:14839737 T>C), RS1001020685 (10:14868788 A>G), RS1001032903 (10:14863133 A>G), RS1001187308 (10:14837106 G>A), RS1001212931 (10:14838184 A>C)

Disease associations

OMIM: gene MIM:610369 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

StudyTraitp-value
GCST003542_153Night sleep phenotypes2.000000e-06
GCST008359_6Response to cognitive-behavioural therapy in anxiety disorder4.000000e-06

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0007820cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169146 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
sodium arseniteaffects expression, decreases expression, increases abundance, increases expression4
Valproic Aciddecreases methylation, increases expression2
aristolochic acid Iincreases expression1
FR900359increases phosphorylation1
triphenyl phosphateaffects expression1
beta-lapachoneincreases expression1
arseniteaffects binding, increases reaction1
tris(1,3-dichloro-2-propyl)phosphatedecreases expression1
cadmium sulfateincreases expression1
di-n-butylphosphoric acidaffects expression1
CGP 52608affects binding, increases reaction1
K 7174decreases expression1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)increases expression1
jinfukangdecreases expression1
Resveratrolaffects cotreatment, increases expression1
Sunitinibincreases expression1
Arecolineincreases expression1
Arsenicincreases abundance, increases expression1
Atrazinedecreases expression1
Cisplatindecreases reaction, increases expression1
Demecolcinedecreases expression1
Ethyl Methanesulfonatedecreases expression1
Folic Aciddecreases expression1
Formaldehydeincreases expression1
Hydrogen Peroxideaffects expression1
Ivermectindecreases expression1
Methyl Methanesulfonatedecreases expression1
Naledaffects expression1
Piroxicamdecreases reaction, increases expression1
Plant Extractsaffects cotreatment, increases expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5152991BindingCovalent binding affinity to human mitochondrial HSP60 expressed in Escherichia coli Rosetta 2 (DE3) cells assessed as modification of cysteine thiol at 4.2 to 60 uM measured after 1 hr by LC-MS/MS analysisBis-aryl-α,β-unsaturated ketone (ABK) chaperonin inhibitors exhibit selective cytotoxicity to colorectal cancer cells that correlates with levels of aberrant HSP60 in the cytosol. — Bioorg Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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Sources 78

This page pulls from 78 datasets indexed by BioBTree:

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