SPINT1

Summary

SPINT1 (serine peptidase inhibitor, Kunitz type 1, HGNC:11246) is a protein-coding gene on chromosome 15q15.1, encoding Kunitz-type protease inhibitor 1 (O43278). Inhibitor of HGFAC.

The protein encoded by this gene is a member of the Kunitz family of serine protease inhibitors. The protein is a potent inhibitor specific for HGF activator and is thought to be involved in the regulation of the proteolytic activation of HGF in injured tissues. Alternative splicing results in multiple variants encoding different isoforms.

Source: NCBI Gene 6692 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 105 total
• Druggable target: yes
• MANE Select transcript: NM_003710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11246
Approved symbol	SPINT1
Name	serine peptidase inhibitor, Kunitz type 1
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	HAI, HAI-1, MANSC2
Ensembl gene	ENSG00000166145
Ensembl biotype	protein_coding
OMIM	605123
Entrez	6692

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 3 retained_intron

ENST00000344051, ENST00000562057, ENST00000563135, ENST00000563656, ENST00000564375, ENST00000566642, ENST00000566928, ENST00000568200, ENST00000568580, ENST00000568823, ENST00000569589, ENST00000907872, ENST00000907873, ENST00000907874, ENST00000907875, ENST00000907876, ENST00000907877, ENST00000907878, ENST00000920941, ENST00000920942, ENST00000920943, ENST00000920944, ENST00000920945, ENST00000943725, ENST00000943726, ENST00000943727, ENST00000943728, ENST00000943729

RefSeq mRNA: 6 — MANE Select: NM_003710 NM_001032367, NM_001386873, NM_001386874, NM_001386875, NM_003710, NM_181642

CCDS: CCDS10067, CCDS45231

Canonical transcript exons

ENST00000562057 — 11 exons

Exon	Start	End
ENSE00001100211	40854060	40854086
ENSE00001100214	40853124	40853251
ENSE00001100221	40854397	40854522
ENSE00001100225	40853489	40853627
ENSE00001696699	40853711	40853881
ENSE00001865623	40856770	40858207
ENSE00003501191	40844490	40845029
ENSE00003538527	40856276	40856323
ENSE00003540805	40855892	40856062
ENSE00003613266	40854639	40854689
ENSE00003920812	40844048	40844186

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.0516 / max 498.4354, expressed in 1042 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146145	12.1215	803
146137	6.6728	800
146142	2.8292	432
146138	1.8363	514
146147	0.3476	221
146140	0.3213	218
146139	0.2731	180
146141	0.1961	134
146146	0.1559	98
146148	0.1253	65

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.47	gold quality
mucosa of transverse colon	UBERON:0004991	98.85	gold quality
jejunal mucosa	UBERON:0000399	98.27	gold quality
skin of abdomen	UBERON:0001416	98.16	gold quality
esophagus mucosa	UBERON:0002469	98.13	gold quality
skin of leg	UBERON:0001511	98.02	gold quality
minor salivary gland	UBERON:0001830	98.00	gold quality
duodenum	UBERON:0002114	97.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.57	gold quality
rectum	UBERON:0001052	97.43	gold quality
mouth mucosa	UBERON:0003729	97.33	gold quality
saliva-secreting gland	UBERON:0001044	97.15	gold quality
islet of Langerhans	UBERON:0000006	97.10	gold quality
metanephros cortex	UBERON:0010533	97.08	gold quality
zone of skin	UBERON:0000014	97.01	gold quality
right uterine tube	UBERON:0001302	96.65	gold quality
oral cavity	UBERON:0000167	96.36	gold quality
body of pancreas	UBERON:0001150	96.29	gold quality
colonic mucosa	UBERON:0000317	96.24	gold quality
pharyngeal mucosa	UBERON:0000355	96.05	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.74	gold quality
placenta	UBERON:0001987	95.60	gold quality
gall bladder	UBERON:0002110	95.38	gold quality
buccal mucosa cell	CL:0002336	95.30	gold quality
pancreas	UBERON:0001264	95.01	gold quality
endometrium epithelium	UBERON:0004811	94.95	gold quality
mammalian vulva	UBERON:0000997	93.60	gold quality
upper lobe of left lung	UBERON:0008952	93.46	gold quality
right lobe of thyroid gland	UBERON:0001119	93.39	gold quality
upper lobe of lung	UBERON:0008948	93.33	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	1413.55
E-MTAB-8205	yes	168.97
E-CURD-114	yes	55.57
E-MTAB-10287	yes	46.56
E-MTAB-5061	yes	25.90
E-GEOD-81547	yes	24.07
E-MTAB-8410	yes	23.73
E-HCAD-10	yes	22.07
E-HCAD-1	yes	14.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, SP1

miRNA regulators (miRDB)

40 targeting SPINT1, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6749-3P	99.00	65.73	1443

Literature-anchored findings (GeneRIF, showing 40)

• HAI-1 (serine peptidase inhibitor, Kunitz type 1) specifically traps active form of HGF activator on cellular surface and regulates HGF activation in pericellular microenvironment. (PMID:11013244)
• hepatocyte growth factor activator inhibitor-1B (new isoform) has roles in various physiological and pathological processes (PMID:12815039)
• 1 serine protease inhibitor genotype is a significant risk factor for chronic obstructive pulmonary disease. (PMID:15994391)
• Data suggest that over-expression of HAI-1 in SW620 cells has weak effect on cell growth in vitro, but can significantly inhibit cell migration/motility. (PMID:16044910)
• HAI-1B is a potential physiological regulator of prostasin function (PMID:16103126)
• The expressions of SNC19/matriptase and its inhibitor HAI-1 are decreased in gastrointestinal cancer tissues (PMID:16273651)
• results show that dysregulation of the matriptase/HAI-1 mRNA ratio occurs early during colorectal cancer carcinogenesis (PMID:16820046)
• Addition of HAI1 blocked the proteolytic activation of STP14 at the cell surface of peritoneal macrophages. (PMID:17389401)
• Prostate cancer cells, after loss of HAI-1, had a significantly increased in vitro invasiveness together with an increase in cellular motility. (PMID:17786295)
• analysis of the regulation of matriptase and HAI-1 with an emphasis on the molecular mechanisms governing its zymogen activation, inhibition by HAI-1, and ectodomain shedding [review] (PMID:17981575)
• Unlike HAI-1 and matriptase, HAI-2 expression is detected in non-epithelial cells of brain and lymph nodes, suggesting that HAI-2 may also be involved in inhibition of serine proteases other than matriptase (PMID:18713750)
• tissue microenvironment regulates the cell surface expression of HAI-1, and thereby may regulate proteolysis and processing of bioactive molecules on the cellular surface (PMID:18769935)
• HAI-1 expression levels were significantly higher in all proliferative prostate diseases and seems to be a marker of prostate epithelial cell proliferation (PMID:18813126)
• HAI-1 and HAI-2 may possibly be therapeutic target for treatment approaches in ovarian cancer. (PMID:19148468)
• Expression of hepatocyte growth factor activator inhibitor type 1 in bronchial epithelial cells are altered by tissue injury to bronchi. (PMID:19222607)
• interactions between HAI-1/SPINT1 and membrane-bound serine proteinases contribute to transcriptional and functional changes involved in EMT in certain carcinoma cells. (PMID:19223533)
• Data suggest that the cellular location of matriptase activation and inhibition, and the secretory route for matriptase-HAI-1 complex may vary along with the functional divergence of different epithelial cells. (PMID:19535514)
• The disease-free and overall survival rates of patients exhibiting high HAI-1 expression were significantly higher than those of patients exhibiting low HAI-1 expression in cervix cancer. (PMID:19578736)
• Expression of HAI-1 in hepatocellular carcinoma is associated with poor prognosis. HAI-1 may be important in neoplasm progression and a new prognostic factor for hepatocellular carcinoma. (PMID:20213201)
• the matriptase-prostasin proteolytic cascade is tightly regulated by two mechanisms: 1) prostasin activation temporally coupled to matriptase autoactivation and 2) HAI-1 rapidly inhibiting not only active matriptase but also active prostasin (PMID:20696767)
• Low HAI-1 is associated with endometrial cancer. (PMID:20715109)
• results suggest that TMPRSS13 functions as an HGF-converting protease, the activity of which may be regulated by HAI-1 (PMID:20977675)
• High-level expression of HAI-1 is retained in the epidermal granular layer. This pattern of expression is retained in most skin disorders. (PMID:21123732)
• HAI-1 regulates pulmonary metastasis of the human pancreatic carcinoma cell line SUIT-2 (PMID:21166957)
• The data suggested that normal epithelial cells use a dual mechanism involving hepatocyte growth factor activator inhibitor-1 and antithrombin to control matriptase and that the antithrombin-based mechanism is lost in the majority of carcinomas. (PMID:21795523)
• HAI-1 and -2 are overexpressed in the liver in cholangiopathies with ductular reactions and are possibly involved in liver fibrosis and hepatic differentiation. (PMID:21898507)
• These results suggest that HAI-1 functions as a physiological regulator of HAT by inhibiting its protease activity and proteolytic activation in airway epithelium.(HAI-1) (PMID:22023801)
• These data suggest that matriptase activity can be rapidly inhibited by HAI-1 and other HAI-1-like protease inhibitors and “locked” in an inactive autoactivation intermediate, all of which places matriptase under very tight control. (PMID:22031598)
• we showed for the first time that MT1-MMP activates matriptase through the cleavage of HAI-1 (PMID:22118498)
• It is suggested that HAI-1 may play an important role in the pathogenesis of castration-resistant prostate cancer (PMID:23393351)
• HAI-1 and HAI-2 influence proliferation and cell fate of NPCs and their expression levels are linked to BMP sign (PMID:23409135)
• Crystal structures of matriptase in complex with its inhibitor hepatocyte growth factor activator inhibitor-1 (PMID:23443661)
• HAI-1 expression correlates with the differentiation status of colorectal epithelia and could serve as a differentiation marker. (PMID:23979832)
• Matriptase activity was suppressed by the expression of HAI-1. (PMID:24147538)
• The results of the present study identified HAI-1 as a favorable prognostic marker for prostate cancer and may indicate that HAI-1 could be a therapeutic target for the treatment of this malignancy. (PMID:24659667)
• Data suggest HAI1 exhibits structural features consistent with classification in MANEC subclass of PAN/apple domain family with unifying features such as two additional disulfide bonds, two extended loop regions, and additional alpha-helical elements. (PMID:25510835)
• HAI-1 may have a critical role in maintaining normal keratinocyte morphology through regulation of PAR-2-dependent p38 mitogen-activated protein kinase signaling. (PMID:25842366)
• the anti-migratory effects seen via gamma-catenin were driven by the expression of hepatocyte growth factor activator inhibitor Type I (HAI-1 or SPINT-1), an upstream inhibitor of the c-MET signaling pathway. (PMID:25925948)
• The findings suggest that the oncogenic activity of hepsin arises not only from elevated expression level but also from depletion of HAI-1, events which together trigger gain-of-function activity impacting HGF/MET signalling and epithelial cohesion (PMID:26165838)
• it was found that the recombinant fusion protein uPA17-34-KPI (kunitz-type protease inhibitor ) inhibited the invasion and metastasis of ovarian tumors (PMID:26166362)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	spint1b	ENSDARG00000012467
danio_rerio	lrp11	ENSDARG00000034076
danio_rerio	wfikkn1	ENSDARG00000101364
danio_rerio	spint1a	ENSDARG00000102332
mus_musculus	Spint1	ENSMUSG00000027315
rattus_norvegicus	Spint1	ENSRNOG00000012811
drosophila_melanogaster	CG7565	FBGN0035833
caenorhabditis_elegans		WBGENE00008304
caenorhabditis_elegans		WBGENE00008449
caenorhabditis_elegans		WBGENE00009386
caenorhabditis_elegans		WBGENE00010792
caenorhabditis_elegans		WBGENE00012186
caenorhabditis_elegans		WBGENE00012814
caenorhabditis_elegans		WBGENE00015355
caenorhabditis_elegans		WBGENE00020648
caenorhabditis_elegans		WBGENE00021939

Paralogs (13): TFPI (ENSG00000003436), EPPIN (ENSG00000101448), TFPI2 (ENSG00000105825), AMBP (ENSG00000106927), LRP11 (ENSG00000120256), WFIKKN1 (ENSG00000127578), KIAA0319 (ENSG00000137261), KIAA0319L (ENSG00000142687), SPINT4 (ENSG00000149651), WFDC8 (ENSG00000158901), SPINT2 (ENSG00000167642), WFIKKN2 (ENSG00000173714), WFDC6 (ENSG00000243543)

Protein

Protein identifiers

Kunitz-type protease inhibitor 1 — O43278 (reviewed: O43278)

Alternative names: Hepatocyte growth factor activator inhibitor type 1

All UniProt accessions (7): O43278, H3BMB6, H3BNW5, H3BR01, H3BSM2, H3BTQ8, H3BVD9

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of HGFAC. Inhibits serine protease activity of ST14/matriptase in vitro. Inhibits serine protease activity of TMPRSS13, via the BPTI/Kunitz inhibitor 1 domain.

Subunit / interactions. Interacts with HGFAC. Interacts with TMPRSS13; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13.

Subcellular location. Secreted. Cytoplasm. Cell membrane.

Domain organisation. This inhibitor contains two inhibitory domains.

Isoforms (2)

UniProt ID	Names	Canonical?
O43278-1	1, HAI-1B	yes
O43278-2	2, HAI-1A

RefSeq proteins (6): NP_001027539, NP_001373802, NP_001373803, NP_001373804, NP_003701, NP_857593 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR002223	Kunitz_BPTI	Domain
IPR011106	MANSC_N	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR013980	MANSC_dom	Domain
IPR020901	Prtase_inh_Kunz-CS	Conserved_site
IPR023415	LDLR_class-A_CS	Conserved_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR036880	Kunitz_BPTI_sf	Homologous_superfamily

Pfam: PF00014, PF00057, PF07502, PF22352

UniProt features (54 total): strand 19, disulfide bond 9, helix 6, domain 4, turn 4, glycosylation site 3, sequence variant 3, site 2, signal peptide 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4ISO	X-RAY DIFFRACTION	2.01
5EZD	X-RAY DIFFRACTION	2.1
4ISL	X-RAY DIFFRACTION	2.29
4ISN	X-RAY DIFFRACTION	2.45
1YC0	X-RAY DIFFRACTION	2.6
5H7V	X-RAY DIFFRACTION	3.82
2MSX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43278-F1	76.95	0.36

Functional residue map

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

Catalytic / active sites (2): 260–261 (reactive bond); 401–402 (reactive bond)

Disulfide bonds (9): 250–300, 259–283, 275–296, 335–347, 342–360, 354–369, 391–441, 400–424, 416–437

Glycosylation sites (3): 523, 66, 235

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6806942	MET Receptor Activation
R-HSA-8852405	Signaling by MST1
R-HSA-162582	Signal Transduction
R-HSA-6806834	Signaling by MET
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 236 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_PLACENTA_BLOOD_VESSEL_DEVELOPMENT

GO Biological Process (10): neural tube closure (GO:0001843), epidermis development (GO:0008544), extracellular matrix organization (GO:0030198), positive regulation of glial cell differentiation (GO:0045687), epithelium development (GO:0060429), branching involved in labyrinthine layer morphogenesis (GO:0060670), placenta blood vessel development (GO:0060674), cellular response to BMP stimulus (GO:0071773), negative regulation of neural precursor cell proliferation (GO:2000178), embryonic placenta development (GO:0001892)

GO Molecular Function (3): serine-type endopeptidase inhibitor activity (GO:0004867), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	2
Signaling by MET	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
tissue development	2
placenta development	2
primary neural tube formation	1
tube closure	1
extracellular structure organization	1
external encapsulating structure organization	1
glial cell differentiation	1
positive regulation of gliogenesis	1
regulation of glial cell differentiation	1
embryonic morphogenesis	1
labyrinthine layer morphogenesis	1
morphogenesis of a branching epithelium	1
blood vessel development	1
cellular response to growth factor stimulus	1
response to BMP	1
negative regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of neural precursor cell proliferation	1
in utero embryonic development	1
embryonic organ development	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
extracellular vesicle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPINT1	HGFAC	Q04756	994
SPINT1	ST14	Q9Y5Y6	929
SPINT1	PRSS8	Q16651	842
SPINT1	HPN	P05981	814
SPINT1	HGF	P14210	767
SPINT1	KLK1	P06870	656
SPINT1	TMPRSS13	Q9BYE2	647
SPINT1	KLK2	P20151	626
SPINT1	CTRB2	Q6GPI1	606
SPINT1	CTRB1	P17538	604
SPINT1	SPINK5	Q9NQ38	537
SPINT1	ZNF347	Q96SE7	503
SPINT1	TJP3	O95049	476
SPINT1	KLK4	Q9Y5K2	465
SPINT1	ABI2	Q9NYB9	425

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SPINT1	HGFAC	psi-mi:“MI:0407”(direct interaction)	0.690
SPINT1	FOXK1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SPINT1	ZNF212	psi-mi:“MI:0915”(physical association)	0.400
HMGB1	SPINT1	psi-mi:“MI:0915”(physical association)	0.370
TENT5A	SPINT1	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
KLK15	SPINT1	psi-mi:“MI:0914”(association)	0.350
ZNF250	SPINT1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
NRG1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
GZMH	DENND11	psi-mi:“MI:0914”(association)	0.350
LYPD4	POTEF	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	ZNF316	psi-mi:“MI:0914”(association)	0.350
AQP3	UBXN8	psi-mi:“MI:0914”(association)	0.350
NAAA	HAX1	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
CLEC2B	ADAM10	psi-mi:“MI:0914”(association)	0.350
KLK15	APAF1	psi-mi:“MI:0914”(association)	0.350
VSIG4	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
GXYLT1	CLGN	psi-mi:“MI:0914”(association)	0.350
ST8SIA5	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): SPINT1 (Affinity Capture-MS), SPINT1 (Two-hybrid), SPINT1 (Affinity Capture-MS), SPINT1 (Affinity Capture-MS), SPINT1 (Affinity Capture-MS), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid), SPINT1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, D3ZT86, D3ZWJ9, D4A929, F8W3R9, G7PWZ3, I6M4H4, O08852, O43157, O43278, O75074, O88204, P17813, P49000, P59383, Q04912, Q17R55, Q499Z3, Q4R3B7, Q4TUC0, Q5ND34, Q62190, Q63961, Q6AXX1, Q76MJ5, Q7TN88, Q7TQH7, Q7Z442, Q7Z4F1, Q80W87, Q80YN4, Q866Y3, Q86VZ4, Q8BHW9, Q8BMN4, Q8BYI8, Q8BZT7

Diamond homologs: A0A1D0BND9, A0A3G2FQK2, A0A6B7FA07, A0A6B7FBD3, A0A6B7FEJ3, A0A6P8HC43, A5X2X1, A8Y7N9, A8Y7P0, A8Y7P6, B1B5I8, B2BS84, B5KF95, B5KL37, B5KL38, B5L5R7, B6RLX2, B6ZIW0, C0HJF3, C0HK74, C0HLB2, C0HMC7, C1IC52, C8YJ94, D8KY58, G3LH89, H2A0N1, H2A0P0, O35536, O43278, O43291, O54819, O76840, P00978, P00990, P00991, P02760, P04365, P04366, P0DJ50

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1352 predictions. Top by Δscore:

Variant	Effect	Δscore
15:40844133:G:GT	donor_gain	1.0000
15:40844984:G:GT	donor_gain	1.0000
15:40844984:G:T	donor_gain	1.0000
15:40845027:GAGG:G	donor_loss	1.0000
15:40845030:GT:G	donor_loss	1.0000
15:40845031:T:G	donor_loss	1.0000
15:40853122:AG:A	acceptor_gain	1.0000
15:40853122:AGG:A	acceptor_gain	1.0000
15:40853123:GG:G	acceptor_gain	1.0000
15:40853123:GGG:G	acceptor_gain	1.0000
15:40853123:GGGT:G	acceptor_gain	1.0000
15:40853247:TAGAG:T	donor_loss	1.0000
15:40853250:AGGTG:A	donor_loss	1.0000
15:40853252:G:C	donor_loss	1.0000
15:40853486:CAGA:C	acceptor_loss	1.0000
15:40853487:A:AG	acceptor_gain	1.0000
15:40853487:AGAG:A	acceptor_gain	1.0000
15:40853488:G:GC	acceptor_gain	1.0000
15:40853488:G:GT	acceptor_loss	1.0000
15:40853488:GA:G	acceptor_gain	1.0000
15:40853488:GAGG:G	acceptor_gain	1.0000
15:40853488:GAGGA:G	acceptor_gain	1.0000
15:40853624:GAAG:G	donor_gain	1.0000
15:40853626:AGG:A	donor_loss	1.0000
15:40853628:GT:G	donor_loss	1.0000
15:40853629:T:A	donor_loss	1.0000
15:40853845:G:GT	donor_gain	1.0000
15:40853845:G:T	donor_gain	1.0000
15:40854387:A:AG	acceptor_gain	1.0000
15:40854390:C:CA	acceptor_gain	1.0000

AlphaMissense

3367 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40853854:T:A	C296S	0.995
15:40853855:G:C	C296S	0.995
15:40853791:T:A	C275S	0.994
15:40853792:G:C	C275S	0.994
15:40853762:G:C	R265P	0.993
15:40853792:G:A	C275Y	0.992
15:40855981:T:C	F419L	0.991
15:40855982:T:G	F419C	0.991
15:40855983:T:A	F419L	0.991
15:40855983:T:G	F419L	0.991
15:40844917:C:G	C121W	0.990
15:40844939:T:C	C129R	0.990
15:40853716:T:A	C250S	0.990
15:40853717:G:C	C250S	0.990
15:40853766:G:C	W266C	0.990
15:40853766:G:T	W266C	0.990
15:40853854:T:C	C296R	0.990
15:40853856:C:G	C296W	0.990
15:40844939:T:A	C129S	0.989
15:40844940:G:C	C129S	0.989
15:40853791:T:C	C275R	0.989
15:40856013:C:A	N429K	0.989
15:40856013:C:G	N429K	0.989
15:40856035:T:A	C437S	0.989
15:40856036:G:C	C437S	0.989
15:40853743:T:A	C259S	0.988
15:40853744:G:C	C259S	0.988
15:40855972:T:A	C416S	0.988
15:40855973:G:C	C416S	0.988
15:40844915:T:C	C121R	0.987

dbSNP variants (sampled 300 via entrez): RS1000134518 (15:40858535 C>T), RS1000424602 (15:40855858 A>G), RS1000715250 (15:40850768 G>C), RS1000763462 (15:40849321 G>A), RS1000876475 (15:40844418 C>A,T), RS1001036455 (15:40854467 G>T), RS1001344664 (15:40857177 A>C), RS1001650895 (15:40856574 G>C), RS1001719110 (15:40844003 G>A), RS1001731471 (15:40844190 A>T), RS1001735733 (15:40850353 G>A), RS1001763846 (15:40850713 A>G), RS1002662690 (15:40847505 G>A), RS1002768305 (15:40851923 A>C), RS1002786222 (15:40842095 G>A,T)

Disease associations

OMIM: gene MIM:605123 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001524_12	Visceral adipose tissue/subcutaneous adipose tissue ratio	3.000000e-06
GCST006585_2671	Blood protein levels	2.000000e-07
GCST010725_23	Malaria	2.000000e-06
GCST010725_38	Malaria	3.000000e-06
GCST010725_80	Malaria	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4742262 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sulforaphane	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
benazol P	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
3-nitrobenzanthrone	decreases expression	1
nutlin 3	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Camptothecin	increases expression	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Hydralazine	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4713754	Binding	Protac activity at CRBN/SPINT1 in human BxPC-3 cells assessed as SPINT1 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6Q6	SEES3-1V human SPINT1, clone1	Embryonic stem cell	Male
CVCL_A6Q7	SEES3-1V human SPINT1, clone2	Embryonic stem cell	Male
CVCL_A6Q8	SEES3-1V human SPINT1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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