HSPBAP1

Summary

HSPBAP1 (HSPB1 associated protein 1, HGNC:16389) is a protein-coding gene on chromosome 3q21.1, encoding HSPB1-associated protein 1 (Q96EW2). May play a role in cellular stress response.

This gene encodes a protein that binds to one of the small heat shock proteins, specifically hsp27. Hsp27 is involved with cell growth and differentiation. This encoded protein was found to be abnormally expressed in patients with intractable epilepsy, although how brain function is affected remains unknown.

Source: NCBI Gene 79663 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_024610

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16389
Approved symbol	HSPBAP1
Name	HSPB1 associated protein 1
Location	3q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22623, PASS1
Ensembl gene	ENSG00000169087
Ensembl biotype	protein_coding
OMIM	608263
Entrez	79663

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000306103, ENST00000463266, ENST00000465044, ENST00000467643, ENST00000471534, ENST00000478601, ENST00000877414, ENST00000877415, ENST00000877416, ENST00000877417, ENST00000936099, ENST00000936100, ENST00000936101, ENST00000936102, ENST00000971052

RefSeq mRNA: 2 — MANE Select: NM_024610 NM_001320728, NM_024610

CCDS: CCDS3017

Canonical transcript exons

ENST00000306103 — 8 exons

Exon	Start	End
ENSE00001817071	122793617	122793831
ENSE00003513857	122755260	122755431
ENSE00003517108	122759224	122759360
ENSE00003586856	122777721	122777906
ENSE00003621091	122741003	122741113
ENSE00003632554	122739999	122740875
ENSE00003665516	122752591	122752674
ENSE00003693783	122768701	122768882

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 95.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8769 / max 146.2397, expressed in 1666 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44147	5.5327	1620
44146	1.1593	596
44148	0.1848	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.19	gold quality
secondary oocyte	CL:0000655	93.13	gold quality
granulocyte	CL:0000094	90.47	gold quality
blood	UBERON:0000178	90.33	gold quality
gastrocnemius	UBERON:0001388	88.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.63	gold quality
monocyte	CL:0000576	88.61	gold quality
mononuclear cell	CL:0000842	88.55	gold quality
leukocyte	CL:0000738	88.46	gold quality
spleen	UBERON:0002106	88.34	gold quality
muscle of leg	UBERON:0001383	88.17	gold quality
endothelial cell	CL:0000115	87.35	gold quality
mucosa of stomach	UBERON:0001199	86.32	gold quality
skeletal muscle organ	UBERON:0014892	85.36	gold quality
muscle organ	UBERON:0001630	85.35	gold quality
skin of abdomen	UBERON:0001416	85.26	gold quality
skin of leg	UBERON:0001511	85.08	gold quality
left lobe of thyroid gland	UBERON:0001120	84.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.91	gold quality
right lobe of thyroid gland	UBERON:0001119	84.76	gold quality
metanephros cortex	UBERON:0010533	84.46	gold quality
thyroid gland	UBERON:0002046	84.28	gold quality
right lung	UBERON:0002167	84.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.00	gold quality
skin of hip	UBERON:0001554	83.89	gold quality
placenta	UBERON:0001987	83.73	gold quality
left adrenal gland cortex	UBERON:0035825	83.59	gold quality
right adrenal gland cortex	UBERON:0035827	83.47	gold quality
right adrenal gland	UBERON:0001233	83.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting HSPBAP1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-12126	98.09	64.82	637
HSA-MIR-4494	97.86	64.93	850
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-514A-3P	96.43	67.77	1048

Literature-anchored findings (GeneRIF, showing 3)

• Molecular cloning and characterization of a novel human gene (HSPBAP1) from human fetal brain (PMID:11978969)
• HSPBAP1 is found extensively in the anterior temporal neocortex of patients with intractable epilepsy. (PMID:17568411)
• Data suggest a novel role and a possible link for HSPBAP1 in promoting prostate cancer cell survival in androgen-deficient conditions by maintaining a basal level of androgen receptor-mediated transcription. (PMID:25359680)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hspbap1	ENSDARG00000033771
mus_musculus	Hspbap1	ENSMUSG00000022849
rattus_norvegicus	Hspbap1	ENSRNOG00000002241
drosophila_melanogaster	HSPBAP1	FBGN0263025

Paralogs (4): KDM8 (ENSG00000155666), TYW5 (ENSG00000162971), HIF1AN (ENSG00000166135), JMJD7 (ENSG00000243789)

Protein

Protein identifiers

HSPB1-associated protein 1 — Q96EW2 (reviewed: Q96EW2)

Alternative names: 27 kDa heat shock protein-associated protein 1, Protein associated with small stress protein 1

All UniProt accessions (1): Q96EW2

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cellular stress response.

Subunit / interactions. Interacts with CRYAB and HSPB1.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed.

Disease relevance. A chromosomal aberration involving HSPBAP1 has been found in a family with renal carcinoma. Translocation t(2;3)(q35;q21) with the putative pseudogene DIRC3. Produces a hybrid mRNA encoding a truncated HSPBAP1 lacking the first 36 amino acids.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96EW2-1	1	yes
Q96EW2-2	2
Q96EW2-3	3

RefSeq proteins (2): NP_001307657, NP_078886* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003347	JmjC_dom	Domain
IPR013296	HSPB1-associated_protein_1	Family
IPR041667	Cupin_8	Domain

Pfam: PF13621

UniProt features (13 total): splice variant 4, sequence conflict 3, region of interest 2, chain 1, domain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EW2-F1	79.79	0.64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, USF_C, MYCMAX_01, BLALOCK_ALZHEIMERS_DISEASE_UP, USF_01, LIAO_METASTASIS, LIAO_HAVE_SOX4_BINDING_SITES, chr3q21, MARSON_BOUND_BY_FOXP3_STIMULATED, SANSOM_APC_TARGETS, SANSOM_APC_MYC_TARGETS, SANSOM_APC_TARGETS_REQUIRE_MYC, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_DIOXYGENASE_ACTIVITY

GO Biological Process (0):

GO Molecular Function (2): 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
dioxygenase activity	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

618 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSPBAP1	HSPB2	Q16082	882
HSPBAP1	HSPB1	P04792	873
HSPBAP1	HSPB3	Q12988	856
HSPBAP1	SLC49A4	Q96SL1	732
HSPBAP1	JMJD4	Q9H9V9	707
HSPBAP1	RIOX1	Q9H6W3	681
HSPBAP1	DIRC1	Q969H9	638
HSPBAP1	LRIG1	Q96JA1	588
HSPBAP1	RIOX2	Q8IUF8	560
HSPBAP1	PPP1R36	Q96LQ0	503
HSPBAP1	C9K0I3	C9K0I3	502
HSPBAP1	JMJD6	Q6NYC1	501
HSPBAP1	PTPRG	P23470	494
HSPBAP1	RNF139	Q8WU17	490
HSPBAP1	RBM46	Q8TBY0	470

IntAct

29 interactions, top by confidence:

A	B	Type	Score
HSPBAP1	ARHGEF5	psi-mi:“MI:0915”(physical association)	0.720
ARHGEF5	HSPBAP1	psi-mi:“MI:0915”(physical association)	0.720
XAF1	AKT1	psi-mi:“MI:0914”(association)	0.670
HSPBAP1	NCALD	psi-mi:“MI:0915”(physical association)	0.590
NUTM1	HSPBAP1	psi-mi:“MI:0915”(physical association)	0.560
HSPBAP1	NUTM1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
SDE2	HSPBAP1	psi-mi:“MI:0915”(physical association)	0.500
HSPBAP1	ABHD10	psi-mi:“MI:0915”(physical association)	0.500
HSPB1	HSPBAP1	psi-mi:“MI:0915”(physical association)	0.400
HSPBAP1	TK1	psi-mi:“MI:0915”(physical association)	0.370
MAGEA1	ANKHD1	psi-mi:“MI:0914”(association)	0.350
FOXD4L6	ANKRD28	psi-mi:“MI:0914”(association)	0.350
HSPBAP1	SERPINC1	psi-mi:“MI:0914”(association)	0.350
KRR1	LGALS7	psi-mi:“MI:0914”(association)	0.350
SDE2	HOXB6	psi-mi:“MI:0914”(association)	0.350
ABHD10	VWA8	psi-mi:“MI:0914”(association)	0.350
IMPDH1	MGST3	psi-mi:“MI:0914”(association)	0.350
MAGEA1	ANKRD17	psi-mi:“MI:0914”(association)	0.350
ARHGEF5	HSPBAP1	psi-mi:“MI:0915”(physical association)	0.000
HSPBAP1	PTN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): HSPBAP1 (Two-hybrid), NUTM1 (Two-hybrid), HSPBAP1 (Affinity Capture-MS), HSPBAP1 (Affinity Capture-MS), HSPBAP1 (Affinity Capture-MS), HSPBAP1 (Affinity Capture-MS), NCALD (Affinity Capture-MS), HSPBAP1 (Affinity Capture-MS), HSPBAP1 (Reconstituted Complex), PTN (Two-hybrid), HSPBAP1 (Two-hybrid), HSPBAP1 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), HSPBAP1 (Affinity Capture-MS), RPS29 (Affinity Capture-MS)

ESM2 similar proteins: A1L3L1, A2RT67, A3KPW7, A4IIA7, A8C750, A8C752, D2HNY3, E1BGQ2, E1C3P4, Q08CL8, Q08DZ8, Q0IHB3, Q149N8, Q1RMU2, Q1RMZ1, Q3MJ13, Q3T1H6, Q5F3F2, Q5RED8, Q5VVJ2, Q5ZJ87, Q66J91, Q69Z66, Q6AYF5, Q6DE97, Q6GR37, Q6P1E7, Q6PNC0, Q6YHU6, Q7TPQ3, Q8BKW4, Q8BXK4, Q8IWR0, Q8IYF3, Q8IZE3, Q8K2I9, Q8NA31, Q8NEN0, Q8NFZ0, Q96EW2

Diamond homologs: A2RSX7, A2RUC4, A8E534, B5XF11, E1C7T6, F4K2M8, Q08BV2, Q2U6D4, Q4IER0, Q4WVD1, Q54LV7, Q58CU3, Q5BH52, Q67ZB6, Q6C3P4, Q96EW2, Q9P3K9, Q5UQY3, Q6AXL5, Q8BK58, B2GUS6, P59723, Q0WVR4, Q1JP61, Q497B8, Q54FG7, Q55DF5, Q5BKC6, Q8BLR9, Q8N371, Q9CXT6, Q9NWT6, O94606, Q3TA59, Q6AY40, Q8RWR1, Q9W0M3, Q9H9V9, Q54FM1, Q96S16

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1678 predictions. Top by Δscore:

Variant	Effect	Δscore
3:122740872:CAAC:C	acceptor_gain	1.0000
3:122740875:CCTAA:C	acceptor_loss	1.0000
3:122740876:CTAA:C	acceptor_loss	1.0000
3:122740877:T:C	acceptor_loss	1.0000
3:122740999:CTAC:C	donor_loss	1.0000
3:122741000:TACC:T	donor_loss	1.0000
3:122741001:ACC:A	donor_loss	1.0000
3:122741002:C:A	donor_loss	1.0000
3:122768696:CTTA:C	donor_loss	1.0000
3:122768697:TTAC:T	donor_loss	1.0000
3:122768699:ACCTG:A	donor_loss	1.0000
3:122768700:C:CA	donor_loss	1.0000
3:122768883:C:CC	acceptor_gain	1.0000
3:122777757:T:C	donor_gain	1.0000
3:122777906:CCTAG:C	acceptor_loss	1.0000
3:122777907:C:CC	acceptor_gain	1.0000
3:122777907:CTA:C	acceptor_loss	1.0000
3:122777908:T:C	acceptor_loss	1.0000
3:122740876:C:CC	acceptor_gain	0.9900
3:122741110:CTTC:C	acceptor_gain	0.9900
3:122741114:C:CC	acceptor_gain	0.9900
3:122741115:T:A	acceptor_loss	0.9900
3:122755432:C:CC	acceptor_gain	0.9900
3:122755436:T:TC	acceptor_gain	0.9900
3:122759226:T:A	donor_gain	0.9900
3:122768879:GGAA:G	acceptor_gain	0.9900
3:122768880:GAA:G	acceptor_gain	0.9900
3:122768880:GAAC:G	acceptor_loss	0.9900
3:122768881:AA:A	acceptor_gain	0.9900
3:122768883:CT:C	acceptor_loss	0.9900

AlphaMissense

3246 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:122752602:A:G	W272R	0.999
3:122752602:A:T	W272R	0.999
3:122755424:A:G	W193R	0.999
3:122755424:A:T	W193R	0.999
3:122759303:A:G	W164R	0.999
3:122759303:A:T	W164R	0.999
3:122759351:A:G	W148R	0.999
3:122759351:A:T	W148R	0.999
3:122752612:A:C	S268R	0.998
3:122752612:A:T	S268R	0.998
3:122752614:T:G	S268R	0.998
3:122752664:A:T	V251D	0.998
3:122755347:A:C	S218R	0.998
3:122755347:A:T	S218R	0.998
3:122755349:T:G	S218R	0.998
3:122759270:G:C	H175D	0.998
3:122752600:C:A	W272C	0.997
3:122752600:C:G	W272C	0.997
3:122752647:G:C	H257D	0.997
3:122752650:A:G	W256R	0.997
3:122752650:A:T	W256R	0.997
3:122755356:A:C	S215R	0.997
3:122755356:A:T	S215R	0.997
3:122755358:T:G	S215R	0.997
3:122755428:T:A	K191N	0.997
3:122755428:T:G	K191N	0.997
3:122752606:G:C	N270K	0.996
3:122752606:G:T	N270K	0.996
3:122755350:G:C	F217L	0.996
3:122755350:G:T	F217L	0.996

dbSNP variants (sampled 300 via entrez): RS1000027824 (3:122743820 G>A), RS1000115234 (3:122768440 C>A), RS1000121196 (3:122763876 C>T), RS1000272972 (3:122787266 G>A), RS1000299953 (3:122753992 G>C), RS1000415567 (3:122753596 T>C), RS1000578592 (3:122766241 T>A), RS1000621934 (3:122747999 A>T), RS1000733263 (3:122747909 T>C,G), RS1000756700 (3:122755574 T>C), RS1000835496 (3:122782278 A>C,T), RS1000888401 (3:122771680 C>G), RS1000901829 (3:122751613 T>C), RS1001048348 (3:122789460 C>T), RS1001070846 (3:122758279 C>T)

Disease associations

OMIM: gene MIM:608263 | 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

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	4
Valproic Acid	affects expression, decreases expression, increases expression	3
bisphenol A	affects methylation	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
aminomethylphosphonic acid (AMPA)	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cypermethrin	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
NSC 689534	affects binding, increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Glyphosate	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects expression	1
Copper	affects binding, increases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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