HSPA12B

Summary

HSPA12B (heat shock protein family A (Hsp70) member 12B, HGNC:16193) is a protein-coding gene on chromosome 20p13, encoding Heat shock 70 kDa protein 12B (Q96MM6).

The protein encoded by this gene contains an atypical heat shock protein 70 (Hsp70) ATPase domain and is therefore a distant member of the mammalian Hsp70 family. This gene may be involved in susceptibility to atherosclerosis. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 116835 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 116 total
• MANE Select transcript: NM_052970

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16193
Approved symbol	HSPA12B
Name	heat shock protein family A (Hsp70) member 12B
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	dJ1009E24.2
Ensembl gene	ENSG00000132622
Ensembl biotype	protein_coding
OMIM	610702
Entrez	116835

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 22 protein_coding

ENST00000254963, ENST00000399701, ENST00000887987, ENST00000887988, ENST00000887989, ENST00000887990, ENST00000887991, ENST00000887992, ENST00000887993, ENST00000887994, ENST00000887995, ENST00000887996, ENST00000887997, ENST00000969451, ENST00000969452, ENST00000969453, ENST00000969454, ENST00000969455, ENST00000969456, ENST00000969457, ENST00000969458, ENST00000969459

RefSeq mRNA: 3 — MANE Select: NM_052970 NM_001197327, NM_001318322, NM_052970

CCDS: CCDS13061, CCDS82596

Canonical transcript exons

ENST00000254963 — 13 exons

Exon	Start	End
ENSE00000858818	3740815	3740912
ENSE00000858821	3745493	3745597
ENSE00000858822	3745915	3746031
ENSE00000858823	3748217	3748391
ENSE00000858824	3749232	3749318
ENSE00000858825	3749750	3749854
ENSE00000858826	3749969	3750227
ENSE00000858827	3750804	3750907
ENSE00001044595	3751511	3753111
ENSE00001938374	3732685	3732794
ENSE00003474167	3738658	3738717
ENSE00003534019	3742284	3742408
ENSE00003555832	3744902	3745088

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 96.94.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1638 / max 40.3230, expressed in 376 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183217	0.9669	355
183218	0.1969	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.94	gold quality
apex of heart	UBERON:0002098	93.27	gold quality
right lung	UBERON:0002167	90.86	gold quality
left ventricle myocardium	UBERON:0006566	87.59	silver quality
heart left ventricle	UBERON:0002084	86.63	gold quality
cardiac ventricle	UBERON:0002082	86.43	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.25	gold quality
omental fat pad	UBERON:0010414	85.99	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.96	gold quality
peritoneum	UBERON:0002358	85.94	gold quality
spleen	UBERON:0002106	85.90	gold quality
cardiac muscle of right atrium	UBERON:0003379	85.72	gold quality
adipose tissue	UBERON:0001013	85.46	gold quality
sperm	CL:0000019	84.89	gold quality
decidua	UBERON:0002450	84.87	gold quality
upper lobe of left lung	UBERON:0008952	84.82	gold quality
upper lobe of lung	UBERON:0008948	84.71	gold quality
epithelium of mammary gland	UBERON:0003244	84.23	gold quality
mammary duct	UBERON:0001765	84.17	gold quality
lower lobe of lung	UBERON:0008949	84.16	silver quality
endothelial cell	CL:0000115	83.31	gold quality
lung	UBERON:0002048	83.31	gold quality
myocardium	UBERON:0002349	83.25	silver quality
endocervix	UBERON:0000458	83.05	gold quality
upper arm skin	UBERON:0004263	82.74	silver quality
vena cava	UBERON:0004087	82.73	silver quality
mammary gland	UBERON:0001911	82.72	gold quality
thoracic mammary gland	UBERON:0005200	82.67	gold quality
body of uterus	UBERON:0009853	82.38	gold quality
heart	UBERON:0000948	82.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting HSPA12B, 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-4692	100.00	67.32	2066
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-342-5P	97.25	64.10	817

Literature-anchored findings (GeneRIF, showing 11)

• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Overexpression of HSPA12B protects against cerebral ischemia/reperfusion injury via a PI3K/Akt-dependent mechanism. (PMID:23046810)
• inhibition of eNOS abrogated the protection of HSPA12B against cardiac dysfunction and remodelling after myocardial infarction (PMID:23729663)
• Plasma extracellular HSPA12B is elevated in both septic mice and patients. (PMID:24977412)
• HSPA12B attenuates lipopolysaccharide-induced inflammatory responses in human umbilical vein endothelial cells via activation of PI3K/Akt signalling pathway. (PMID:25545050)
• Results indicate that HSPA12B stimulates lung tumor growth via a Cox-2-dependent mechanism. The present study identified HSPA12B as a novel facilitator of lung tumor growth. (PMID:25909170)
• The HSPA12B might regulate the expression and activity of SSeCKS to promote astrocyte inflammatory activation and release of inflammatory mediators, such as TNF-alpha and IL-1beta in spinal cord primary astroglial cultures exposed to LPS treatment. (PMID:26428665)
• HSPA12B plays a protective role in vascular endothelial barrier dysfunction by preserving the endothelial permeability during sepsis. (PMID:27083952)
• HSPA12B overexpression attenuated acute myocardial I/R injury. This protective action of HSPA12B was mediated, at least in part, through activation of PI3K/Akt/mTOR signaling. (PMID:27644317)
• miR4505 downregulates the expression of HSPA12B and aggravates the LPSinduced vascular endothelial cell injury. (PMID:29115487)
• Novel Role of Endothelial Derived Exosomal HSPA12B in Regulating Macrophage Inflammatory Responses in Polymicrobial Sepsis. (PMID:32457753)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspa12b	ENSDARG00000030307
mus_musculus	Hspa12b	ENSMUSG00000074793
rattus_norvegicus	Hspa12b	ENSRNOG00000021244

Paralogs (4): ALPK1 (ENSG00000073331), EEF2K (ENSG00000103319), HSPA12A (ENSG00000165868), ALPK2 (ENSG00000198796)

Protein

Protein identifiers

Heat shock 70 kDa protein 12B — Q96MM6 (reviewed: Q96MM6)

Alternative names: Heat shock protein family A member 12B

All UniProt accessions (3): Q96MM6, B7ZLP2, Q5JX83

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Highest expression in muscle and heart. Lower levels in liver and kidney.

Similarity. Belongs to the heat shock protein 70 family.

RefSeq proteins (3): NP_001184256, NP_001305251, NP_443202* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043129	ATPase_NBD	Homologous_superfamily

UniProt features (11 total): modified residue 6, sequence variant 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MM6-F1	82.83	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 25, 29, 42, 44, 46, 276

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 58 (showing top): GGGTGGRR_PAX4_03, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_TUBE_MORPHOGENESIS, GOMF_ADENYL_NUCLEOTIDE_BINDING, MIKKELSEN_ES_ICP_WITH_H3K4ME3_AND_H3K27ME3, LEE_BMP2_TARGETS_UP, PEDRIOLI_MIR31_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_REGULATION_OF_HSF1_MEDIATED_HEAT_SHOCK_RESPONSE, REACTOME_CELLULAR_RESPONSE_TO_HEAT_STRESS, REACTOME_CELLULAR_RESPONSES_TO_STIMULI, GSE5503_MLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_UP, GOBP_TUBE_DEVELOPMENT, GSE10240_CTRL_VS_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN

GO Biological Process (2): angiogenesis (GO:0001525), endothelial cell migration (GO:0043542)

GO Molecular Function (3): ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (0):

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
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell migration	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1

Protein interactions and networks

STRING

3541 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPA12B	HSPA1A	P08107	803
HSPA12B	HSPA4	P34932	761
HSPA12B	HSPA13	P48723	690
HSPA12B	HSPA14	Q0VDF9	624
HSPA12B	B0YIZ1	B0YIZ1	606
HSPA12B	HSPA9	P30036	579
HSPA12B	HSPA4L	O95757	546
HSPA12B	HSPA6	P17066	525
HSPA12B	HSPA1L	P34931	522
HSPA12B	DNAJC5B	Q9UF47	470
HSPA12B	HSPA5	P11021	462
HSPA12B	GPR137	Q96N19	443
HSPA12B	HSPA8	P11142	438
HSPA12B	FERD3L	Q96RJ6	438
HSPA12B	HSPH1	Q92598	432
HSPA12B	HYOU1	Q9Y4L1	432

IntAct

53 interactions, top by confidence:

A	B	Type	Score
HSPA12A	HSPA12B	psi-mi:“MI:0915”(physical association)	0.740
HSPA12B	KRT31	psi-mi:“MI:0915”(physical association)	0.720
KRT31	HSPA12B	psi-mi:“MI:0915”(physical association)	0.720
HSPA12B	KRT40	psi-mi:“MI:0915”(physical association)	0.560
HSPA12B	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	HSPA12B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	HSPA12B	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	HSPA12B	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	HSPA12B	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	HSPA12B	psi-mi:“MI:0915”(physical association)	0.560
KRT34	HSPA12B	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	HSPA12B	psi-mi:“MI:0915”(physical association)	0.560
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
PODXL	HSPA12A	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
HSPA12B	EEF2K	psi-mi:“MI:0914”(association)	0.530
PODXL	HSPA12A	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
MALSU1	VWA8	psi-mi:“MI:0914”(association)	0.350
HSPA12B	VWA8	psi-mi:“MI:0914”(association)	0.350
BSG	METTL15	psi-mi:“MI:0914”(association)	0.350
FCGR3A	RTL8C	psi-mi:“MI:0914”(association)	0.350
ZNG1A	TCERG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): HSPA12B (Two-hybrid), KRT40 (Two-hybrid), NOTCH2NL (Two-hybrid), HSPA12B (Affinity Capture-MS), HSPA12B (Affinity Capture-MS), HSPA12B (Affinity Capture-MS), HSPA12B (Two-hybrid), HSPA12B (Two-hybrid), HSPA12B (Two-hybrid), HSPA12A (Two-hybrid), EFEMP2 (Two-hybrid), KRTAP10-8 (Two-hybrid), CYSRT1 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid)

ESM2 similar proteins: A0JNU3, A2AKE7, A6H603, A6QQ74, D3ZBP4, F1MH07, O43542, Q149M9, Q2T9W4, Q2TA43, Q2V057, Q32KZ2, Q32L91, Q3ZBE0, Q49HH9, Q49KI5, Q4QR76, Q4R317, Q4R6Q3, Q4R821, Q5JWF8, Q5REQ1, Q5XIK1, Q641W9, Q643R3, Q68FW7, Q6AY16, Q6NVG1, Q76HM9, Q86U10, Q8CG27, Q8K4F6, Q8TC94, Q8TDG2, Q8TDY3, Q8TDZ2, Q8VCZ9, Q8VDP3, Q8VEI3, Q95JK8

Diamond homologs: O43301, Q8K0U4, Q96MM6, Q9CZJ2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2555 predictions. Top by Δscore:

Variant	Effect	Δscore
20:3732793:AGGT:A	donor_loss	1.0000
20:3732794:GGT:G	donor_loss	1.0000
20:3732795:G:C	donor_loss	1.0000
20:3732796:T:G	donor_loss	1.0000
20:3740872:A:T	donor_gain	1.0000
20:3740913:G:GG	donor_gain	1.0000
20:3742279:TGCA:T	acceptor_loss	1.0000
20:3742281:CA:C	acceptor_loss	1.0000
20:3742282:A:AG	acceptor_gain	1.0000
20:3742282:AG:A	acceptor_loss	1.0000
20:3742283:G:GT	acceptor_gain	1.0000
20:3742283:GA:G	acceptor_gain	1.0000
20:3742283:GAA:G	acceptor_gain	1.0000
20:3742283:GAAA:G	acceptor_gain	1.0000
20:3742283:GAAAC:G	acceptor_gain	1.0000
20:3742405:TGAG:T	donor_loss	1.0000
20:3742406:GAGG:G	donor_loss	1.0000
20:3742407:AG:A	donor_loss	1.0000
20:3742409:GTG:G	donor_loss	1.0000
20:3742410:T:A	donor_loss	1.0000
20:3744896:CCGCA:C	acceptor_loss	1.0000
20:3744897:CGCAG:C	acceptor_loss	1.0000
20:3744899:CAGG:C	acceptor_loss	1.0000
20:3744900:A:AC	acceptor_loss	1.0000
20:3744900:A:AG	acceptor_gain	1.0000
20:3744900:AG:A	acceptor_gain	1.0000
20:3744901:G:GG	acceptor_gain	1.0000
20:3744901:GG:G	acceptor_gain	1.0000
20:3744901:GGAA:G	acceptor_gain	1.0000
20:3745084:CCACG:C	donor_gain	1.0000

AlphaMissense

4425 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:3742339:A:T	D66V	1.000
20:3742356:A:C	S72R	1.000
20:3742358:T:A	S72R	1.000
20:3742358:T:G	S72R	1.000
20:3744958:T:C	L108P	1.000
20:3745067:G:C	K144N	1.000
20:3745067:G:T	K144N	1.000
20:3745963:T:A	W203R	1.000
20:3745963:T:C	W203R	1.000
20:3745979:C:A	P208H	1.000
20:3745987:T:A	W211R	1.000
20:3745987:T:C	W211R	1.000
20:3746004:G:C	K216N	1.000
20:3746004:G:T	K216N	1.000
20:3746015:G:C	R220P	1.000
20:3748265:G:A	E242K	1.000
20:3748266:A:T	E242V	1.000
20:3748267:G:C	E242D	1.000
20:3748267:G:T	E242D	1.000
20:3748269:C:A	P243H	1.000
20:3748278:C:A	A246D	1.000
20:3749795:T:C	L328P	1.000
20:3750086:T:C	L387P	1.000
20:3750111:G:C	K395N	1.000
20:3750111:G:T	K395N	1.000
20:3750820:T:A	W440R	1.000
20:3750820:T:C	W440R	1.000
20:3750839:T:A	L446H	1.000
20:3751672:G:C	G523R	1.000
20:3751672:G:T	G523C	1.000

dbSNP variants (sampled 300 via entrez): RS1000354855 (20:3743118 T>G), RS1000407158 (20:3742542 G>A), RS1000448222 (20:3747860 G>A), RS1000496065 (20:3747520 A>G), RS1000651724 (20:3747878 A>G), RS1000812809 (20:3753114 C>T), RS1000850135 (20:3735420 C>A), RS1001007129 (20:3741084 G>A,T), RS1001014095 (20:3741382 A>G), RS1001318442 (20:3750522 G>A,C), RS1001680085 (20:3744471 A>G), RS1001740887 (20:3738265 C>T), RS1001803890 (20:3740148 A>G,T), RS1002145163 (20:3732864 T>G), RS1002168616 (20:3748991 C>G)

Disease associations

OMIM: gene MIM:610702 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001523_15	Visceral adipose tissue adjusted for BMI	7.000000e-06
GCST008181_9	Spontaneous preterm birth without premature rupture of membranes	7.000000e-06
GCST90013407_186	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-41

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006917	spontaneous preterm birth
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
2,4,6-tribromophenol	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Silver Nitrate	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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