SPINT2 (serine peptidase inhibitor, Kunitz type 2)

Gene

• Entrez ID: 10653
• Gene name: Serine peptidase inhibitor, Kunitz type 2
• Gene symbol: SPINT2
• Synonyms: DIAR3, HAI-2, HAI2, Kop, PB
• Chromosome: 19
• Chromosome location: 19q13.2
• Summary: This gene encodes a transmembrane protein with two extracellular Kunitz domains that inhibits a variety of serine proteases. The protein inhibits HGF activator which prevents the formation of active hepatocyte growth factor. This gene is a putative tumor

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs112576957	T>A,C	Pathogenic	Splice donor variant
rs121908403	A>G	Pathogenic	Coding sequence variant, missense variant
rs121908404	A>T	Pathogenic	Initiator codon variant, missense variant
rs606231154	G>A	Pathogenic	Splice acceptor variant
rs606231155	T>C	Pathogenic	Splice donor variant
rs606231284	G>A	Pathogenic	Coding sequence variant, missense variant
rs780880496	G>A,T	Pathogenic	Missense variant, coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT574111	hsa-miR-583	PAR-CLIP	20371350
MIRT574110	hsa-miR-4677-3p	PAR-CLIP	20371350
MIRT574109	hsa-miR-4679	PAR-CLIP	20371350
MIRT574108	hsa-miR-3182	PAR-CLIP	20371350
MIRT574107	hsa-miR-539-5p	PAR-CLIP	20371350
MIRT574108	hsa-miR-3182	PAR-CLIP	27292025
MIRT574110	hsa-miR-4677-3p	PAR-CLIP	27292025
MIRT574109	hsa-miR-4679	PAR-CLIP	27292025
MIRT574107	hsa-miR-539-5p	PAR-CLIP	27292025
MIRT574111	hsa-miR-583	PAR-CLIP	27292025
MIRT574111	hsa-miR-583	PAR-CLIP	20371350
MIRT574110	hsa-miR-4677-3p	PAR-CLIP	20371350
MIRT574109	hsa-miR-4679	PAR-CLIP	20371350
MIRT574108	hsa-miR-3182	PAR-CLIP	20371350
MIRT574107	hsa-miR-539-5p	PAR-CLIP	20371350
MIRT1384639	hsa-miR-1237	CLIP-seq
MIRT1384640	hsa-miR-1248	CLIP-seq
MIRT1384641	hsa-miR-1273	CLIP-seq
MIRT1384642	hsa-miR-1298	CLIP-seq
MIRT1384643	hsa-miR-1910	CLIP-seq
MIRT1384644	hsa-miR-2355-5p	CLIP-seq
MIRT1384645	hsa-miR-3124-3p	CLIP-seq
MIRT1384646	hsa-miR-342-3p	CLIP-seq
MIRT1384647	hsa-miR-3613-3p	CLIP-seq
MIRT1384648	hsa-miR-3691-5p	CLIP-seq
MIRT1384649	hsa-miR-377	CLIP-seq
MIRT1384650	hsa-miR-3909	CLIP-seq
MIRT1384651	hsa-miR-3919	CLIP-seq
MIRT1384652	hsa-miR-3942-3p	CLIP-seq
MIRT1384653	hsa-miR-4287	CLIP-seq
MIRT1384654	hsa-miR-4320	CLIP-seq
MIRT1384655	hsa-miR-4418	CLIP-seq
MIRT1384656	hsa-miR-4474-5p	CLIP-seq
MIRT1384657	hsa-miR-4477a	CLIP-seq
MIRT1384658	hsa-miR-4494	CLIP-seq
MIRT1384659	hsa-miR-4508	CLIP-seq
MIRT1384660	hsa-miR-4685-3p	CLIP-seq
MIRT1384661	hsa-miR-4690-3p	CLIP-seq
MIRT1384662	hsa-miR-4752	CLIP-seq
MIRT1384663	hsa-miR-4762-5p	CLIP-seq
MIRT1384664	hsa-miR-4789-3p	CLIP-seq
MIRT1384665	hsa-miR-499-3p	CLIP-seq
MIRT1384666	hsa-miR-499a-3p	CLIP-seq
MIRT1384667	hsa-miR-509-3-5p	CLIP-seq
MIRT1384668	hsa-miR-509-5p	CLIP-seq
MIRT1384669	hsa-miR-539	CLIP-seq
MIRT1384670	hsa-miR-581	CLIP-seq
MIRT1384671	hsa-miR-664	CLIP-seq
MIRT1384672	hsa-miR-888	CLIP-seq
MIRT1384673	hsa-miR-1205	CLIP-seq
MIRT1384674	hsa-miR-151-5p	CLIP-seq
MIRT1384675	hsa-miR-151b	CLIP-seq
MIRT1384676	hsa-miR-1972	CLIP-seq
MIRT1384677	hsa-miR-3125	CLIP-seq
MIRT1384678	hsa-miR-3167	CLIP-seq
MIRT1384679	hsa-miR-3916	CLIP-seq
MIRT1384655	hsa-miR-4418	CLIP-seq
MIRT1384658	hsa-miR-4494	CLIP-seq
MIRT1384659	hsa-miR-4508	CLIP-seq
MIRT1384680	hsa-miR-4737	CLIP-seq
MIRT1384667	hsa-miR-509-3-5p	CLIP-seq
MIRT1384668	hsa-miR-509-5p	CLIP-seq
MIRT1384681	hsa-miR-765	CLIP-seq
MIRT1384682	hsa-miR-876-5p	CLIP-seq
MIRT1384683	hsa-miR-877	CLIP-seq
MIRT1384639	hsa-miR-1237	CLIP-seq
MIRT1384640	hsa-miR-1248	CLIP-seq
MIRT2115140	hsa-miR-186	CLIP-seq
MIRT1384643	hsa-miR-1910	CLIP-seq
MIRT2115141	hsa-miR-203	CLIP-seq
MIRT1384644	hsa-miR-2355-5p	CLIP-seq
MIRT2115142	hsa-miR-3117-3p	CLIP-seq
MIRT2115143	hsa-miR-3133	CLIP-seq
MIRT2115144	hsa-miR-3169	CLIP-seq
MIRT1384646	hsa-miR-342-3p	CLIP-seq
MIRT1384649	hsa-miR-377	CLIP-seq
MIRT1384651	hsa-miR-3919	CLIP-seq
MIRT1384652	hsa-miR-3942-3p	CLIP-seq
MIRT1384653	hsa-miR-4287	CLIP-seq
MIRT1384656	hsa-miR-4474-5p	CLIP-seq
MIRT1384660	hsa-miR-4685-3p	CLIP-seq
MIRT1384661	hsa-miR-4690-3p	CLIP-seq
MIRT2115145	hsa-miR-4759	CLIP-seq
MIRT1384664	hsa-miR-4789-3p	CLIP-seq
MIRT1384665	hsa-miR-499-3p	CLIP-seq
MIRT1384666	hsa-miR-499a-3p	CLIP-seq
MIRT1384669	hsa-miR-539	CLIP-seq
MIRT2115146	hsa-miR-548ae	CLIP-seq
MIRT2115147	hsa-miR-548aj	CLIP-seq
MIRT2115148	hsa-miR-548am	CLIP-seq
MIRT2115149	hsa-miR-548x	CLIP-seq
MIRT2115150	hsa-miR-642a	CLIP-seq
MIRT1384673	hsa-miR-1205	CLIP-seq
MIRT1384674	hsa-miR-151-5p	CLIP-seq
MIRT1384675	hsa-miR-151b	CLIP-seq
MIRT1384677	hsa-miR-3125	CLIP-seq
MIRT1384678	hsa-miR-3167	CLIP-seq
MIRT1384679	hsa-miR-3916	CLIP-seq
MIRT1384655	hsa-miR-4418	CLIP-seq
MIRT1384658	hsa-miR-4494	CLIP-seq
MIRT1384659	hsa-miR-4508	CLIP-seq
MIRT1384680	hsa-miR-4737	CLIP-seq
MIRT1384667	hsa-miR-509-3-5p	CLIP-seq
MIRT1384668	hsa-miR-509-5p	CLIP-seq
MIRT1384681	hsa-miR-765	CLIP-seq
MIRT1384682	hsa-miR-876-5p	CLIP-seq
MIRT1384683	hsa-miR-877	CLIP-seq
MIRT2115140	hsa-miR-186	CLIP-seq
MIRT2115141	hsa-miR-203	CLIP-seq
MIRT2115142	hsa-miR-3117-3p	CLIP-seq
MIRT2115143	hsa-miR-3133	CLIP-seq
MIRT2115144	hsa-miR-3169	CLIP-seq
MIRT2115145	hsa-miR-4759	CLIP-seq
MIRT1384669	hsa-miR-539	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001843	Process	Neural tube closure	IEA
GO:0004866	Function	Endopeptidase inhibitor activity	TAS	9115294
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IBA	21873635
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IDA	19185281
GO:0005576	Component	Extracellular region	TAS	9346890
GO:0005737	Component	Cytoplasm	IDA	11606055
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0007163	Process	Establishment or maintenance of cell polarity	IEA
GO:0010951	Process	Negative regulation of endopeptidase activity	IEA
GO:0016021	Component	Integral component of membrane	IEA
GO:0022408	Process	Negative regulation of cell-cell adhesion	IDA	19592578
GO:0060672	Process	Epithelial cell morphogenesis involved in placental branching	IEA
GO:0071711	Process	Basement membrane organization	IEA
GO:0071773	Process	Cellular response to BMP stimulus	IEA
GO:2000146	Process	Negative regulation of cell motility	IDA	19592578
GO:2000178	Process	Negative regulation of neural precursor cell proliferation	IEA

Other IDs

• MIM: 605124
• HGNC: 11247
• e!Ensembl: ENSG00000167642

Protein

• UniProt ID: O43291
• Protein name: Kunitz-type protease inhibitor 2 (Hepatocyte growth factor activator inhibitor type 2) (HAI-2) (Placental bikunin)
• Protein function: Inhibitor of HGFAC (PubMed:9346890). Also inhibits plasmin, and plasma and tissue kallikrein (PubMed:9115294). Inhibits serine protease activity of TMPRSS13 (PubMed:20977675, PubMed:28710277). Inhibits serine protease activity of ST14/matriptase
• PDB: 4U32
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00014	Kunitz_BPTI	37 → 89	Kunitz/Bovine pancreatic trypsin inhibitor domain	Domain
  PF00014	Kunitz_BPTI	132 → 184	Kunitz/Bovine pancreatic trypsin inhibitor domain	Domain

• Sequence:

  MAQLCGLRRSRAFLALLGSLLLSGVLAADRERSIHDFCLVSKVVGRCRASMPRWWYNVTD
  GSCQLFVYGGCDGNSNNYLTKEECLKKCATVTENATGDLATSRNAADSSVPSAPRRQDSE
  DHSSDMFNYEEYCTANAVTGPCRASFPRWYFDVERNSCNNFIYGGCRGNKNSYRSEEACM
  LRCFRQQENPPLPLGSKVVVLAGLFVMVLILFLGASMVYLIRVARRNQERALRTVWSSGD
  DKEQLVKNTYVL

• Sequence length: 252

Pathways

Reactome:

MET Receptor Activation
Signaling by MST1

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anencephaly	Iniencephaly, Exencephaly	rs773607884	24722141
Carcinoma	Carcinoma, Carcinoma, Spindle-Cell, Undifferentiated carcinoma	rs121912654, rs555607708, rs786202962, rs1564055259	16316942
Congenital secretory diarrhea	Congenital secretory diarrhea, sodium type (disorder)	rs606231154, rs121908403, rs606231155, rs112576957, rs121908404, rs386833491, rs121913030, rs121913032, rs121913033, rs386833444, rs386833445, rs386833447, rs386833448, rs386833449, rs386833450, rs386833451, rs386833452, rs386833453, rs386833454, rs386833455, rs386833456, rs386833457, rs386833458, rs386833459, rs386833460, rs386833461, rs386833463, rs386833465, rs386833466, rs386833467, rs386833468, rs386833469, rs121913031, rs386833471, rs386833472, rs386833473, rs386833474, rs386833475, rs386833476, rs386833477, rs386833478, rs386833479, rs386833481, rs386833482, rs386833483, rs386833484, rs386833485, rs386833486, rs386833488, rs386833489, rs386833490, rs606231284, rs869312806, rs776026092, rs766076524, rs869320692, rs869312807, rs869320759, rs144524702, rs766583286, rs780880496, rs1018933248, rs1584403556	17786112, 19185281, 24142340
Nasopharyngeal carcinoma	Nasopharyngeal carcinoma	rs200046052	20512145
Neural tube defect	Neural Tube Defects	rs121918220, rs121434297, rs137853061, rs137853062, rs3127334, rs267607167, rs267607168, rs387907204, rs139365610, rs137955120, rs786201015, rs786201016, rs768434408, rs777661576, rs747846362, rs200137991, rs780014899, rs574132670, rs786204013, rs147257424, rs763539350, rs776483190, rs757259023, rs781461462, rs762921297, rs1114167354, rs557643577, rs147277149, rs765586205, rs377443637, rs1563593163, rs1303000329, rs1565818580, rs986604359, rs1293600145, rs114727354, rs146357218, rs768980918, rs140277700, rs139645527, rs750323424, rs368321176, rs1579619636, rs893229476, rs754990692, rs763079713, rs1593037878, rs747100389, rs372056091, rs1593083585, rs778121031, rs748778907, rs776969786, rs1189298981, rs375908206, rs1734858651, rs778738842	24722141
Polydactyly	Polydactyly	rs1583729398, rs121917709, rs1583734240, rs121917714, rs397507422, rs398122899, rs587776959, rs386833752, rs1057518698, rs1060499558, rs755938967, rs1375768446, rs1309855392, rs1565601979, rs748321474, rs368652620, rs1562587032, rs760694987	17786112
Prostate cancer	Malignant neoplasm of prostate, Prostate carcinoma	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	19767754, 29892016, 19767754

Unknown
Disease name	Disease term	dbSNP ID	References
Acrania	Acrania		24722141
Anaplastic carcinoma	Anaplastic carcinoma		16316942
Choanal atresia	Choanal Atresia
Coloboma of optic disc	Coloboma of optic disc		24142340
Corneal erosion	Corneal erosion
Craniorachischisis	Craniorachischisis		24722141
Diastematomyelia	Diastematomyelia		24722141
Diverticular diseases	Diverticular Diseases		30177863
Hexadactyly	Hexadactyly		17786112
Intestinal epithelial dysplasia	Intestinal epithelial dysplasia		24142340
Neurenteric cyst	Neurenteric Cyst		24722141
Primary tethered cord syndrome	Tethered Cord Syndrome		24722141
Spinal cord myelodysplasia	Spinal Cord Myelodysplasia		24722141