HSPA13

Summary

HSPA13 (heat shock protein family A (Hsp70) member 13, HGNC:11375) is a protein-coding gene on chromosome 21q11.2, encoding Heat shock 70 kDa protein 13 (P48723). Has peptide-independent ATPase activity. It is a selective cancer dependency (DepMap: 12.7% of cell lines).

The protein encoded by this gene is a member of the heat shock protein 70 family and is found associated with microsomes. Members of this protein family play a role in the processing of cytosolic and secretory proteins, as well as in the removal of denatured or incorrectly-folded proteins. The encoded protein contains an ATPase domain and has been shown to associate with a ubiquitin-like protein.

Source: NCBI Gene 6782 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 68 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 12.7% of screened cell lines
• MANE Select transcript: NM_006948

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11375
Approved symbol	HSPA13
Name	heat shock protein family A (Hsp70) member 13
Location	21q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000155304
Ensembl biotype	protein_coding
OMIM	601100
Entrez	6782

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000285667, ENST00000478035, ENST00000903931, ENST00000903932

RefSeq mRNA: 1 — MANE Select: NM_006948 NM_006948

CCDS: CCDS13567

Canonical transcript exons

ENST00000285667 — 5 exons

Exon	Start	End
ENSE00001020226	14383095	14383146
ENSE00001020231	14378199	14378412
ENSE00001280391	14371115	14374284
ENSE00003578743	14375652	14375819
ENSE00003608679	14381203	14381543

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.2381 / max 709.2069, expressed in 1806 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189758	37.1410	1806
189759	0.0499	8
189760	0.0472	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.14	gold quality
cartilage tissue	UBERON:0002418	96.58	gold quality
cortical plate	UBERON:0005343	96.50	gold quality
islet of Langerhans	UBERON:0000006	95.87	gold quality
ganglionic eminence	UBERON:0004023	95.80	gold quality
adrenal tissue	UBERON:0018303	95.31	gold quality
endothelial cell	CL:0000115	95.06	gold quality
pigmented layer of retina	UBERON:0001782	94.44	gold quality
corpus epididymis	UBERON:0004359	94.44	gold quality
retina	UBERON:0000966	94.41	gold quality
type B pancreatic cell	CL:0000169	93.82	gold quality
embryo	UBERON:0000922	93.65	gold quality
caput epididymis	UBERON:0004358	93.54	gold quality
orbitofrontal cortex	UBERON:0004167	93.07	gold quality
cauda epididymis	UBERON:0004360	92.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.59	gold quality
CA1 field of hippocampus	UBERON:0003881	92.55	gold quality
superior frontal gyrus	UBERON:0002661	92.14	gold quality
choroid plexus epithelium	UBERON:0003911	92.06	gold quality
seminal vesicle	UBERON:0000998	91.69	gold quality
postcentral gyrus	UBERON:0002581	91.68	gold quality
superficial temporal artery	UBERON:0001614	91.66	gold quality
entorhinal cortex	UBERON:0002728	91.60	gold quality
substantia nigra pars compacta	UBERON:0001965	91.58	gold quality
medial globus pallidus	UBERON:0002477	91.49	gold quality
stromal cell of endometrium	CL:0002255	90.97	gold quality
parietal lobe	UBERON:0001872	90.79	gold quality
globus pallidus	UBERON:0001875	90.78	gold quality
superior vestibular nucleus	UBERON:0007227	90.78	gold quality
heart right ventricle	UBERON:0002080	90.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

133 targeting HSPA13, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-381-3P	99.93	71.87	2854

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• in the Japanese population, STCH might be a new candidate for conferring susceptibility to gastric cancer (PMID:16087163)
• These results suggest that STCH has a role in cell survival via modulation of the TRAIL-mediated cell death pathway. (PMID:18793616)
• An entirely novel path is revealed toward therapeutic intervention of tauopathies by inhibition of the previously untargeted ATPase activity of Hsp70. (PMID:19793966)
• novel role of STCH in the regulation of pHi through site-specific interactions with NBCe1-B and NHE1 and subsequent modulation of membrane transporter expression. (PMID:23303189)
• Hspa13 Promotes Plasma Cell Production and Antibody Secretion. (PMID:32547538)
• Differential Effects of STCH and Stress-Inducible Hsp70 on the Stability and Maturation of NKCC2. (PMID:33672238)
• Heat shock protein Hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation. (PMID:36244454)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspa13	ENSDARG00000040984
mus_musculus	Hspa13	ENSMUSG00000032932
rattus_norvegicus	Hspa13	ENSRNOG00000060979
caenorhabditis_elegans		WBGENE00006059

Paralogs (13): HSPA5 (ENSG00000044574), HSPA8 (ENSG00000109971), HSPA9 (ENSG00000113013), HSPH1 (ENSG00000120694), HSPA2 (ENSG00000126803), HYOU1 (ENSG00000149428), HSPA4L (ENSG00000164070), HSPA4 (ENSG00000170606), HSPA6 (ENSG00000173110), HSPA14 (ENSG00000187522), HSPA1B (ENSG00000204388), HSPA1A (ENSG00000204389), HSPA1L (ENSG00000204390)

Protein

Protein identifiers

Heat shock 70 kDa protein 13 — P48723 (reviewed: P48723)

Alternative names: Heat shock protein family A member 13, Microsomal stress-70 protein ATPase core, Stress-70 protein chaperone microsome-associated 60 kDa protein

All UniProt accessions (2): P48723, A0A140VK72

UniProt curated annotations — full annotation on UniProt →

Function. Has peptide-independent ATPase activity.

Subunit / interactions. Binds UBQLN2.

Subcellular location. Microsome. Endoplasmic reticulum.

Tissue specificity. Constitutively expressed in all tissues.

Similarity. Belongs to the heat shock protein 70 family.

RefSeq proteins (1): NP_008879* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013126	Hsp_70_fam	Family
IPR018181	Heat_shock_70_CS	Conserved_site
IPR042048	HSPA13	Family
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00012

UniProt features (5 total): signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48723-F1	87.43	0.69

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response

MSigDB gene sets: 191 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_MSH3, BROWNE_HCMV_INFECTION_8HR_UP, MORF_BRCA1, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, LANG_MYB_FAMILY_TARGETS, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, RIZKI_TUMOR_INVASIVENESS_3D_DN, MODULE_66, GOBP_PROTEIN_MATURATION, AAACCAC_MIR140, GOBP_PROTEIN_FOLDING, SCHLOSSER_SERUM_RESPONSE_DN, MORF_RAP1A

GO Biological Process (2): protein refolding (GO:0042026), 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 (7): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), intracellular membrane-bounded organelle (GO:0043231), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to heat stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein folding	2
ATP-dependent activity	2
intracellular membrane-bounded organelle	2
intracellular anatomical structure	2
cellular anatomical structure	2
cytoplasm	2
cellular process	1
protein maturation	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
molecular_function	1
protein folding chaperone	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
endomembrane system	1
membrane	1
cell periphery	1
membrane-bounded organelle	1
intracellular organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

3845 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPA13	UBQLN2	Q9UHD9	984
HSPA13	UBQLN4	Q9NRR5	827
HSPA13	UBQLN1	Q9UMX0	812
HSPA13	LIPI	Q6XZB0	750
HSPA13	HSPA12A	O43301	744
HSPA13	B0YIZ1	B0YIZ1	695
HSPA13	HSPA12B	Q96MM6	690
HSPA13	STIP1	P31948	674
HSPA13	PLEKHG4	Q58EX7	547
HSPA13	QKI	Q96PU8	542
HSPA13	RBPMS	Q93062	515
HSPA13	RBM17	Q96I25	511
HSPA13	PQBP1	O60828	510
HSPA13	HSP90B1	P14625	503
HSPA13	ATXN1	P54253	497

IntAct

140 interactions, top by confidence:

A	B	Type	Score
HSPA13	UBQLN1	psi-mi:“MI:0915”(physical association)	0.830
UBQLN1	HSPA13	psi-mi:“MI:0915”(physical association)	0.830
SGTA	HSPA13	psi-mi:“MI:0915”(physical association)	0.720
HSPA13	SGTA	psi-mi:“MI:0915”(physical association)	0.720
HSPA13	UBQLN1	psi-mi:“MI:0915”(physical association)	0.670
HSPA13	SGTB	psi-mi:“MI:0915”(physical association)	0.670
HSPA13	UBQLN2	psi-mi:“MI:0915”(physical association)	0.670
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
DKKL1	DENND11	psi-mi:“MI:0914”(association)	0.640
HSPA13	B4GALT5	psi-mi:“MI:0915”(physical association)	0.560
HSPA13	CRYGA	psi-mi:“MI:0915”(physical association)	0.560
PRSS22	PPM1A	psi-mi:“MI:0914”(association)	0.560
HSPA13	POLE4	psi-mi:“MI:0915”(physical association)	0.550
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
TOR1AIP1	TXN	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
HSPA13	BAG6	psi-mi:“MI:0915”(physical association)	0.370
HSPA13	RMI1	psi-mi:“MI:0915”(physical association)	0.370
HSPA13	SSR1	psi-mi:“MI:0915”(physical association)	0.370
TANK	CNOT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (154): HSPA13 (Two-hybrid), UBQLN1 (Two-hybrid), HSPA13 (Affinity Capture-MS), HSPA13 (Affinity Capture-MS), HSPA13 (Affinity Capture-MS), UBQLN1 (Two-hybrid), HSPA13 (Two-hybrid), HSPA13 (Affinity Capture-MS), HSPA13 (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), HSPA13 (Affinity Capture-MS), HSPA13 (Proximity Label-MS), HSPA13 (Affinity Capture-MS), HSPA13 (Affinity Capture-MS), HSPA13 (Affinity Capture-MS)

ESM2 similar proteins: A1AWL7, A3M561, A8GMI8, A8GR49, B0BWJ7, B0VD55, B0VNV8, B2HZI1, B7H3H4, B7I5P9, C3PMP2, C4K0Z7, D1J722, D4A2Z8, E9PU17, E9PX95, F4IM84, G7LCC3, O35162, O52960, O88967, O96566, P48723, P52914, P70106, P80595, P99502, Q05931, Q18411, Q1RJ70, Q2TBX4, Q3UW68, Q4UKL3, Q4V339, Q55154, Q5E780, Q5JTY5, Q5R8D9, Q5RIA9, Q5XI69

Diamond homologs: A0A509AJG0, A2Q0Z1, A5A8V7, F5HB71, G0SCU5, G3I8R9, J9VZ70, O35162, O59855, O73885, O97125, P02827, P06761, P07823, P08108, P08418, P09435, P0DMV8, P0DMV9, P0DMW0, P0DMW1, P10591, P10592, P11021, P11142, P11147, P14659, P17066, P17156, P17879, P19120, P19208, P19378, P20029, P20163, P22202, P27420, P29843, P29844, P34930

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	5	24.8×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	11	16.1×	9e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	55
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
625662	GRCh37/hg19 21p11.1-q21.2(chr21:10944001-25730963)	Pathogenic

SpliceAI

654 predictions. Top by Δscore:

Variant	Effect	Δscore
21:14375646:TCTTA:T	donor_loss	1.0000
21:14375647:CTTA:C	donor_loss	1.0000
21:14375648:TTACC:T	donor_loss	1.0000
21:14375649:TACCA:T	donor_loss	1.0000
21:14375650:A:AC	donor_gain	1.0000
21:14375650:A:T	donor_loss	1.0000
21:14375651:C:CC	donor_gain	1.0000
21:14375651:CCAGA:C	donor_gain	1.0000
21:14375677:C:A	donor_gain	1.0000
21:14375680:T:TA	donor_gain	1.0000
21:14375729:A:AC	donor_gain	1.0000
21:14375815:CAGTC:C	acceptor_gain	1.0000
21:14375817:GTC:G	acceptor_gain	1.0000
21:14375817:GTCC:G	acceptor_loss	1.0000
21:14375818:TC:T	acceptor_gain	1.0000
21:14375818:TCCT:T	acceptor_loss	1.0000
21:14375819:CC:C	acceptor_gain	1.0000
21:14375820:C:CC	acceptor_gain	1.0000
21:14375828:T:TC	acceptor_gain	1.0000
21:14375832:T:C	acceptor_gain	1.0000
21:14375832:T:TC	acceptor_gain	1.0000
21:14378193:TGTTA:T	donor_loss	1.0000
21:14378194:GTTAC:G	donor_loss	1.0000
21:14378195:TTA:T	donor_loss	1.0000
21:14378196:TAC:T	donor_loss	1.0000
21:14378197:A:AT	donor_loss	1.0000
21:14378198:C:T	donor_loss	1.0000
21:14381199:TTA:T	donor_loss	1.0000
21:14381200:TA:T	donor_loss	1.0000
21:14381201:A:AC	donor_gain	1.0000

AlphaMissense

3073 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:14381270:T:A	K100I	1.000
21:14381362:G:C	S69R	1.000
21:14381362:G:T	S69R	1.000
21:14381364:T:G	S69R	1.000
21:14373703:C:G	A444P	0.999
21:14373711:G:T	A441D	0.999
21:14373712:C:G	A441P	0.999
21:14373717:C:T	G439E	0.999
21:14373718:C:G	G439R	0.999
21:14373718:C:T	G439R	0.999
21:14373804:C:G	R410P	0.999
21:14373816:C:A	G406V	0.999
21:14373816:C:T	G406E	0.999
21:14373817:C:A	G406W	0.999
21:14373817:C:G	G406R	0.999
21:14373817:C:T	G406R	0.999
21:14374137:A:G	L299P	0.999
21:14374145:T:A	K296N	0.999
21:14374145:T:G	K296N	0.999
21:14374269:C:A	G255V	0.999
21:14374269:C:T	G255E	0.999
21:14374270:C:G	G255R	0.999
21:14374270:C:T	G255R	0.999
21:14375661:C:G	A247P	0.999
21:14375693:A:G	L236P	0.999
21:14375700:A:G	S234P	0.999
21:14375708:A:G	L231P	0.999
21:14375725:G:C	D225E	0.999
21:14375725:G:T	D225E	0.999
21:14375726:T:G	D225A	0.999

dbSNP variants (sampled 300 via entrez): RS1000206146 (21:14381057 G>A), RS1000726163 (21:14385113 C>CA), RS1001020582 (21:14373295 T>C), RS1001284093 (21:14379654 T>C), RS1001474415 (21:14372940 T>C), RS1001576630 (21:14374031 G>A), RS1001664002 (21:14380733 G>A), RS1002287917 (21:14378089 T>C), RS1002318712 (21:14374779 G>A), RS1002574135 (21:14385049 G>C), RS1002655197 (21:14378820 A>C,G), RS1002665126 (21:14379116 T>G), RS1002993100 (21:14372511 A>G), RS1003404258 (21:14376926 C>A), RS1003762574 (21:14377104 T>C)

Disease associations

OMIM: gene MIM:601100 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
bisphenol A	affects expression, increases expression, decreases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Air Pollutants	increases expression, decreases expression, increases abundance	3
Estradiol	increases expression	3
Tetrachlorodibenzodioxin	decreases expression, affects expression	3
mono-(2-ethylhexyl)phthalate	decreases expression, decreases methylation, increases abundance	2
Acetaminophen	increases expression	2
Arsenic	increases abundance, increases expression, affects expression, affects cotreatment	2
Nickel	increases expression	2
Valproic Acid	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
tri-o-cresyl phosphate	increases expression	1
cupric oxide	increases expression	1
hydroquinone	increases expression	1
brequinar	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1N9	Abcam K-562 HSPA13 KO	Cancer cell line	Female
CVCL_D2JU	Abcam Raji HSPA13 KO	Cancer cell line	Male
CVCL_UQ75	Abcam Jurkat HSPA13 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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