HS1BP3

Summary

HS1BP3 (HCLS1 binding protein 3, HGNC:24979) is a protein-coding gene on chromosome 2p24.1, encoding HCLS1-binding protein 3 (Q53T59). May be a modulator of IL-2 signaling.

The protein encoded by this gene shares similarity with mouse Hs1bp3, an Hcls1/Hs1-interacting protein that may be involved in lymphocyte activation.

Source: NCBI Gene 64342 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_022460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24979
Approved symbol	HS1BP3
Name	HCLS1 binding protein 3
Location	2p24.1
Locus type	gene with protein product
Status	Approved
Aliases	HS1-BP3, FLJ14249
Ensembl gene	ENSG00000118960
Ensembl biotype	protein_coding
OMIM	609359
Entrez	64342

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 nonsense_mediated_decay

ENST00000304031, ENST00000402541, ENST00000406618, ENST00000415264, ENST00000445102, ENST00000446825, ENST00000458740, ENST00000631166, ENST00000651498, ENST00000897119, ENST00000897120, ENST00000897121

RefSeq mRNA: 1 — MANE Select: NM_022460 NM_022460

CCDS: CCDS1700

Canonical transcript exons

ENST00000304031 — 7 exons

Exon	Start	End
ENSE00000715860	20645340	20645505
ENSE00001319210	20617818	20619245
ENSE00001830605	20651032	20651098
ENSE00003478169	20624732	20624892
ENSE00003486168	20623896	20624031
ENSE00003544902	20638436	20638652
ENSE00003665602	20640973	20641180

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 91.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5896 / max 85.6573, expressed in 1790 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27145	15.5638	1790
27146	0.0258	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus muscularis layer	UBERON:0035833	91.96	gold quality
lower esophagus	UBERON:0013473	91.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.78	gold quality
popliteal artery	UBERON:0002250	91.08	gold quality
tibial artery	UBERON:0007610	91.07	gold quality
aorta	UBERON:0000947	90.84	gold quality
ascending aorta	UBERON:0001496	90.62	gold quality
thoracic aorta	UBERON:0001515	90.56	gold quality
mucosa of stomach	UBERON:0001199	90.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.24	gold quality
right adrenal gland	UBERON:0001233	90.23	gold quality
right adrenal gland cortex	UBERON:0035827	90.05	gold quality
left adrenal gland cortex	UBERON:0035825	89.69	gold quality
left adrenal gland	UBERON:0001234	89.49	gold quality
adrenal cortex	UBERON:0001235	89.41	gold quality
descending thoracic aorta	UBERON:0002345	89.38	gold quality
monocyte	CL:0000576	89.17	gold quality
mononuclear cell	CL:0000842	88.88	gold quality
leukocyte	CL:0000738	88.73	gold quality
left coronary artery	UBERON:0001626	88.73	gold quality
adrenal gland	UBERON:0002369	88.67	gold quality
coronary artery	UBERON:0001621	88.61	gold quality
apex of heart	UBERON:0002098	88.24	gold quality
saphenous vein	UBERON:0007318	88.02	gold quality
right coronary artery	UBERON:0001625	87.99	gold quality
right lobe of liver	UBERON:0001114	87.71	gold quality
adult mammalian kidney	UBERON:0000082	87.67	gold quality
granulocyte	CL:0000094	87.56	gold quality
cardia of stomach	UBERON:0001162	87.55	silver quality
right atrium auricular region	UBERON:0006631	87.36	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.81
E-MTAB-6379	no	445.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRD4, CTCF, JMJD6

miRNA regulators (miRDB)

57 targeting HS1BP3, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4292	99.16	65.57	1767

Literature-anchored findings (GeneRIF, showing 5)

• The 828C–>G mutation causes a substitution of a glycine for an alanine residue in the HS1-BP3 protein. It was found in 2 unrelated patients with familial essential tremor. (PMID:15699368)
• HS1PB3 protein is mutated in essential tremor combined with Parkinson disease. (PMID:16116142)
• Results do not support a role for these DRD3 and HS1BP3 variants in PD. (PMID:19524641)
• Results suggest that HS1BP3 regulates apoptosis via HS1 and stimulates AP-1-mediated transcription. (PMID:21699750)
• HS1BP3 is localized to ATG16L1- and ATG9-positive autophagosome precursors and we show that HS1BP3 binds phosphatidic acid (PA) through its PX domain. Furthermore, we find the total PA content of cells to be significantly upregulated in the absence of HS1BP3. (PMID:28004827)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hs1bp3	ENSDARG00000034222
mus_musculus	Hs1bp3	ENSMUSG00000020605
rattus_norvegicus	Hs1bp3	ENSRNOG00000006062

Protein

Protein identifiers

HCLS1-binding protein 3 — Q53T59 (reviewed: Q53T59)

Alternative names: HS1-binding protein 3

All UniProt accessions (9): A0A0D9SFN1, A0A494C0K6, B5MC96, Q53T59, F6TR53, F8WDN8, H7BZ19, H7BZZ1, H7C0Y9

UniProt curated annotations — full annotation on UniProt →

Function. May be a modulator of IL-2 signaling.

Subunit / interactions. Binds HCLS1. Interacts with the SH3 domain of HCLS1 in vitro.

RefSeq proteins (1): NP_071905* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR036871	PX_dom_sf	Homologous_superfamily
IPR037901	HS1BP3_PX	Domain
IPR039701	HS1BP3	Family

Pfam: PF00787

UniProt features (18 total): modified residue 6, sequence variant 4, region of interest 3, compositionally biased region 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53T59-F1	67.69	0.33

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): 139, 194, 249, 337, 1, 3

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 123 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, MODULE_255, MODULE_317, GTGCCTT_MIR506, BLALOCK_ALZHEIMERS_DISEASE_UP, HU_GENOTOXIN_ACTION_DIRECT_VS_INDIRECT_24HR, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, TGGAAA_NFAT_Q4_01, GRYDER_PAX3FOXO1_TOP_ENHANCERS, MODULE_69, BOYLAN_MULTIPLE_MYELOMA_C_CLUSTER_DN, GOMF_PHOSPHATIDYLINOSITOL_BINDING, GOMF_LIPID_BINDING, GOMF_PHOSPHOLIPID_BINDING, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_DN

GO Biological Process (1): regulation of apoptotic process (GO:0042981)

GO Molecular Function (2): phosphatidylinositol binding (GO:0035091), protein binding (GO:0005515)

GO Cellular Component (2): mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
apoptotic process	1
regulation of programmed cell death	1
anion binding	1
binding	1
endomembrane system	1

Protein interactions and networks

STRING

608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HS1BP3	CHP1	Q99653	763
HS1BP3	HCLS1	P14317	648
HS1BP3	LDAH	Q9H6V9	615
HS1BP3	TOR2A	Q5JU69	551
HS1BP3	REEP4	Q9H6H4	501
HS1BP3	SNX10	Q9Y5X0	462
HS1BP3	SNX21	Q969T3	459
HS1BP3	LINGO4	Q6UY18	452
HS1BP3	DRD3	P35462	447
HS1BP3	SNX18	Q96RF0	444
HS1BP3	GDF7	Q7Z4P5	442
HS1BP3	SNX20	Q7Z614	441
HS1BP3	LINGO2	Q7L985	417
HS1BP3	NKAIN3	Q8N8D7	402
HS1BP3	LINGO1	Q96FE5	396

IntAct

30 interactions, top by confidence:

A	B	Type	Score
HS1BP3	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
HS1BP3	GSN	psi-mi:“MI:0915”(physical association)	0.560
HS1BP3	PMP22	psi-mi:“MI:0915”(physical association)	0.560
HS1BP3	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
TMED3	HS1BP3	psi-mi:“MI:0914”(association)	0.530
VGLL4	YAP1	psi-mi:“MI:0914”(association)	0.530
TCP10L	RNF40	psi-mi:“MI:0914”(association)	0.350
ANTXR2	ELOA	psi-mi:“MI:0914”(association)	0.350
HS1BP3	PDXDC1	psi-mi:“MI:0914”(association)	0.350
HS1BP3	TAF5L	psi-mi:“MI:0914”(association)	0.350
RWDD2B	CMPK1	psi-mi:“MI:0914”(association)	0.350
ANTXR2	HS1BP3	psi-mi:“MI:0914”(association)	0.350
HS1BP3	MPO	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
KIAA1191	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
SNRNP27	BPNT1	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
CEP170	ERVK3-1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (57): HS1BP3 (Two-hybrid), HS1BP3 (Affinity Capture-MS), HS1BP3 (Affinity Capture-MS), NAA38 (Co-fractionation), HS1BP3 (Proximity Label-MS), ABTB2 (Affinity Capture-MS), PDXDC1 (Affinity Capture-MS), HS1BP3 (Affinity Capture-MS), RAD50 (Affinity Capture-MS), HS1BP3 (Affinity Capture-MS), HS1BP3 (Affinity Capture-MS), HS1BP3 (Affinity Capture-MS), HS1BP3 (Proximity Label-MS), HS1BP3 (Affinity Capture-MS), C20orf194 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB4, A4IFK0, A5PMU4, O54824, O62666, O62674, O62675, O62676, O62677, O62678, O75128, P49796, P59672, P78524, P97432, Q0V8R5, Q14005, Q14596, Q32LQ1, Q3B7M3, Q3TC93, Q501R9, Q53GL0, Q53T59, Q5BJM5, Q5F3C8, Q5JV73, Q5NBX1, Q5RC94, Q5SUE8, Q5SYB0, Q5T7N3, Q5VT97, Q6P9J5, Q80TI1, Q80UZ0, Q80XA6, Q86XL3, Q8C4S8, Q8K124

Diamond homologs: Q3TC93, Q53T59

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1377 predictions. Top by Δscore:

Variant	Effect	Δscore
2:20624032:C:CC	acceptor_gain	1.0000
2:20624726:A:AC	donor_gain	1.0000
2:20624727:C:CC	donor_gain	1.0000
2:20624727:CTT:C	donor_loss	1.0000
2:20624729:TA:T	donor_loss	1.0000
2:20624730:A:AC	donor_gain	1.0000
2:20624730:AC:A	donor_loss	1.0000
2:20624730:ACGGT:A	donor_gain	1.0000
2:20624731:C:CA	donor_gain	1.0000
2:20624731:CG:C	donor_gain	1.0000
2:20624731:CGG:C	donor_gain	1.0000
2:20624731:CGGT:C	donor_gain	1.0000
2:20624731:CGGTC:C	donor_gain	1.0000
2:20624749:T:TA	donor_gain	1.0000
2:20624888:TGGAG:T	acceptor_gain	1.0000
2:20624889:GGAG:G	acceptor_gain	1.0000
2:20624890:GAG:G	acceptor_gain	1.0000
2:20624891:AG:A	acceptor_gain	1.0000
2:20624893:C:A	acceptor_loss	1.0000
2:20624893:C:CC	acceptor_gain	1.0000
2:20624902:C:CT	acceptor_gain	1.0000
2:20638463:T:TA	donor_gain	1.0000
2:20638466:T:TA	donor_gain	1.0000
2:20638469:T:TA	donor_gain	1.0000
2:20638651:ACC:A	acceptor_loss	1.0000
2:20638652:CCTG:C	acceptor_loss	1.0000
2:20638653:C:CG	acceptor_loss	1.0000
2:20638654:T:C	acceptor_loss	1.0000
2:20641014:T:TA	donor_gain	1.0000
2:20645334:GCTCA:G	donor_loss	1.0000

AlphaMissense

2563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:20645350:A:T	V63D	0.997
2:20645417:A:G	Y41H	0.995
2:20645473:A:G	L22P	0.995
2:20645344:A:G	F65S	0.994
2:20645379:C:A	K53N	0.994
2:20645379:C:G	K53N	0.994
2:20645417:A:C	Y41D	0.993
2:20645416:T:G	Y41S	0.992
2:20640978:A:G	F134S	0.990
2:20641044:A:G	F112S	0.990
2:20641055:C:A	R108S	0.990
2:20641055:C:G	R108S	0.990
2:20641080:A:T	V100D	0.990
2:20645383:A:G	F52S	0.990
2:20645382:G:C	F52L	0.989
2:20645382:G:T	F52L	0.989
2:20645384:A:G	F52L	0.989
2:20641083:A:G	F99S	0.987
2:20641168:A:C	Y71D	0.986
2:20645381:T:C	K53E	0.986
2:20645473:A:C	L22R	0.986
2:20645473:A:T	L22Q	0.986
2:20641023:A:T	V119D	0.985
2:20645467:A:T	V24E	0.985
2:20645404:A:T	V45E	0.984
2:20641172:T:A	K69N	0.982
2:20641172:T:G	K69N	0.982
2:20645343:G:C	F65L	0.982
2:20645343:G:T	F65L	0.982
2:20645345:A:G	F65L	0.982

dbSNP variants (sampled 300 via entrez): RS1000063753 (2:20568998 G>A), RS1000104558 (2:20587387 C>G,T), RS1000181905 (2:20594390 C>T), RS1000197065 (2:20564072 T>C), RS1000209363 (2:20637393 C>A), RS1000234333 (2:20605245 G>T), RS1000259304 (2:20589406 T>C), RS1000260295 (2:20555049 C>T), RS1000334309 (2:20554441 G>A), RS1000338632 (2:20626725 C>T), RS1000360736 (2:20631297 T>C), RS1000364757 (2:20650857 G>A,C), RS1000386129 (2:20584490 C>T), RS1000405570 (2:20642190 T>C), RS1000438775 (2:20584180 G>A,C)

Disease associations

OMIM: gene MIM:609359 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006004_10	Low density lipoprotein cholesterol levels	6.000000e-59
GCST006034_30	Total cholesterol levels	2.000000e-39
GCST006479_42	Diverticular disease	4.000000e-06
GCST008155_46	Waist-hip ratio	4.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0009959	diverticular disease
EFO:0004343	waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
zinc chromate	increases abundance, increases expression	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Ivermectin	decreases expression	1
Mercury	decreases expression	1
Methotrexate	decreases expression	1
Quercetin	increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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