SERPINI2

Summary

SERPINI2 (serpin family I member 2, HGNC:8945) is a protein-coding gene on chromosome 3q26.1, encoding Serpin I2 (O75830).

The gene encodes a member of a family of proteins that acts as inhibitors of serine proteases. These proteins function in the regulation of a variety of physiological processes, including coagulation, fibrinolysis, development, malignancy, and inflammation. Expression of the encoded protein may be downregulated during pancreatic carcinogenesis. Alternative splicing results in multiple transcript variants for this gene.

Source: NCBI Gene 5276 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_006217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8945
Approved symbol	SERPINI2
Name	serpin family I member 2
Location	3q26.1
Locus type	gene with protein product
Status	Approved
Aliases	TSA2004, MEPI
Ensembl gene	ENSG00000114204
Ensembl biotype	protein_coding
OMIM	605587
Entrez	5276

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000264677, ENST00000461846, ENST00000465031, ENST00000466903, ENST00000467583, ENST00000471111, ENST00000476257, ENST00000495108

RefSeq mRNA: 3 — MANE Select: NM_006217 NM_001012303, NM_001394327, NM_006217

CCDS: CCDS3200

Canonical transcript exons

ENST00000264677 — 9 exons

Exon	Start	End
ENSE00000780136	167446392	167446481
ENSE00000780137	167449316	167449402
ENSE00000780138	167452936	167453033
ENSE00000780139	167465206	167465398
ENSE00000780140	167465479	167465673
ENSE00000780141	167467055	167467285
ENSE00000826118	167441933	167442185
ENSE00001831569	167474003	167474042
ENSE00003635048	167471588	167471844

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 99.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4531 / max 512.6483, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45448	0.4531	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.54	gold quality
pancreas	UBERON:0001264	93.59	gold quality
right uterine tube	UBERON:0001302	91.64	gold quality
bronchial epithelial cell	CL:0002328	87.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.94	gold quality
islet of Langerhans	UBERON:0000006	85.32	gold quality
epithelium of bronchus	UBERON:0002031	85.26	gold quality
bronchus	UBERON:0002185	83.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.62	gold quality
epithelial cell of pancreas	CL:0000083	77.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.13	silver quality
monocyte	CL:0000576	72.79	gold quality
mononuclear cell	CL:0000842	72.35	gold quality
caudate nucleus	UBERON:0001873	71.15	gold quality
choroid plexus epithelium	UBERON:0003911	71.11	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.75	gold quality
leukocyte	CL:0000738	70.51	gold quality
nucleus accumbens	UBERON:0001882	69.87	gold quality
oviduct epithelium	UBERON:0004804	69.85	gold quality
fallopian tube	UBERON:0003889	69.80	gold quality
ventricular zone	UBERON:0003053	66.33	gold quality
corpus callosum	UBERON:0002336	66.19	gold quality
right lung	UBERON:0002167	66.02	gold quality
right atrium auricular region	UBERON:0006631	65.72	gold quality
hypothalamus	UBERON:0001898	65.23	gold quality
amygdala	UBERON:0001876	65.15	gold quality
diaphragm	UBERON:0001103	65.03	gold quality
cardiac atrium	UBERON:0002081	64.36	gold quality
granulocyte	CL:0000094	63.54	gold quality
olfactory bulb	UBERON:0002264	62.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	29.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting SERPINI2, 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-590-3P	99.96	74.34	6478
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-4524B-3P	95.52	64.12	964
HSA-MIR-574-3P	92.35	64.27	41

Literature-anchored findings (GeneRIF, showing 1)

• The findings indicate that SERPINI2 is a promising candidate for further investigations of the genetic susceptibility to myopia. (PMID:22110064)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpini2	ENSMUSG00000034139
rattus_norvegicus	Serpini2	ENSRNOG00000009903

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Serpin I2 — O75830 (reviewed: O75830)

Alternative names: Myoepithelium-derived serine protease inhibitor, Pancpin, Pancreas-specific protein TSA2004, Peptidase inhibitor 14

All UniProt accessions (4): A0A8V8PL11, C9J7N5, C9JWE1, O75830

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Expressed in pancreas and adipose tissues.

Similarity. Belongs to the serpin family.

RefSeq proteins (3): NP_001012303, NP_001381256, NP_006208* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (8 total): glycosylation site 3, sequence variant 2, signal peptide 1, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75830-F1	86.30	0.70

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 (1): 357–358 (reactive bond)

Glycosylation sites (3): 202, 207, 306

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, chr3q26, BLALOCK_ALZHEIMERS_DISEASE_UP, MODULE_99, SCHLOSSER_SERUM_RESPONSE_DN, RYTTCCTG_ETS2_B, FOXJ2_02, TGGAAA_NFAT_Q4_01, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, WILSON_PROTEASES_AT_TUMOR_BONE_INTERFACE_DN, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, YOSHIMURA_MAPK8_TARGETS_UP, WUNDER_INFLAMMATORY_RESPONSE_AND_CHOLESTEROL_UP

GO Biological Process (0):

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

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINI2	PI15	O43692	694
SERPINI2	PI16	Q6UXB8	670
SERPINI2	CPB1	P15086	654
SERPINI2	PLAT	P00750	585
SERPINI2	RPE65	Q16518	583
SERPINI2	PLAU	P00749	521
SERPINI2	WDR49	Q8IV35	514
SERPINI2	PLG	P00747	507
SERPINI2	PLA2G1B	P04054	506
SERPINI2	ZBBX	A8MT70	450
SERPINI2	CEP290	O15078	432
SERPINI2	ARFGEF3	Q5TH69	389
SERPINI2	FAM124A	Q86V42	389
SERPINI2	ZNF80	P51504	374
SERPINI2	ADAM18	Q9Y3Q7	348
SERPINI2	PNLIPRP1	P54315	348

IntAct

33 interactions, top by confidence:

A	B	Type	Score
UBQLN1	SERPINI2	psi-mi:“MI:0915”(physical association)	0.900
SERPINI2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.900
SERPINI2	SGTB	psi-mi:“MI:0915”(physical association)	0.670
UBQLN1	SERPINI2	psi-mi:“MI:0915”(physical association)	0.560
SERPINI2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
SGTA	SERPINI2	psi-mi:“MI:0915”(physical association)	0.560
SERPINI2	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SERPINI2	HPCAL1	psi-mi:“MI:0915”(physical association)	0.560
SERPINI2	NUP58	psi-mi:“MI:0915”(physical association)	0.400
SERPINI2	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
BAG6	SERPINI2	psi-mi:“MI:0915”(physical association)	0.370
PRKCE	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
SERPINI2	LEPR	psi-mi:“MI:0914”(association)	0.350
SERPINI2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.000
SERPINI2	SGTB	psi-mi:“MI:0915”(physical association)	0.000
SERPINI2	SGTA	psi-mi:“MI:0915”(physical association)	0.000
SERPINI2	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
SERPINI2	HPCAL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): UBQLN1 (Two-hybrid), UBQLN1 (Two-hybrid), SERPINI2 (Biochemical Activity), SERPINI2 (Two-hybrid), SGTB (Two-hybrid), BAG6 (Two-hybrid), SERPINI2 (Two-hybrid), HPCAL1 (Two-hybrid), UBQLN1 (Two-hybrid), UBQLN2 (Two-hybrid), SGTB (Two-hybrid), SERPINI2 (Affinity Capture-MS), HIST1H2BH (Proximity Label-MS), NUPL1 (Proximity Label-MS), SNIP1 (Affinity Capture-MS)

ESM2 similar proteins: A2I7N3, B0UYL8, O75830, P01015, P01017, P01019, P05121, P05154, P05155, P05544, P05545, P05546, P07759, P09006, P11859, P13909, P20757, P20961, P22777, P29622, P31211, P32759, P47776, P49182, P50448, P50449, P70458, P79335, P97290, Q03734, Q5I2A0, Q5RCR2, Q5RDA8, Q60396, Q62975, Q63556, Q64268, Q6P4P1, Q6P734, Q7TMF5

Diamond homologs: A0A090BX51, A0A0K8RCY5, A0A0K8RJ89, A0A0K8RJV9, A5PJK0, A9RA96, B0CMB0, B1MTB7, B1MTC3, B2KI30, B3RFC3, B4USX2, E2RVI8, O02739, O08800, O35684, O54757, O54758, O54759, O54760, O73790, O73860, O75635, O75830, P01008, P01011, P01012, P01014, P05120, P05619, P12388, P17475, P19104, P22323, P22325, P22922, P23035, P29508, P29524, P30740

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2070 predictions. Top by Δscore:

Variant	Effect	Δscore
3:167442186:C:CC	acceptor_gain	1.0000
3:167465227:T:TA	donor_gain	1.0000
3:167467054:CCAT:C	donor_gain	1.0000
3:167467084:A:AC	donor_gain	1.0000
3:167467084:AT:A	donor_gain	1.0000
3:167467084:ATCAT:A	donor_gain	1.0000
3:167467085:T:C	donor_gain	1.0000
3:167467147:T:TA	donor_gain	1.0000
3:167442181:TGATT:T	acceptor_gain	0.9900
3:167442183:ATTC:A	acceptor_loss	0.9900
3:167442184:TT:T	acceptor_gain	0.9900
3:167442184:TTCTA:T	acceptor_loss	0.9900
3:167442185:TC:T	acceptor_loss	0.9900
3:167442186:C:A	acceptor_loss	0.9900
3:167442187:T:A	acceptor_loss	0.9900
3:167449237:A:AC	donor_gain	0.9900
3:167449238:C:CC	donor_gain	0.9900
3:167449240:T:TA	donor_gain	0.9900
3:167450648:A:C	donor_gain	0.9900
3:167465228:C:A	donor_gain	0.9900
3:167467067:TTTC:T	donor_gain	0.9900
3:167467068:TTCT:T	donor_gain	0.9900
3:167467070:C:CT	donor_gain	0.9900
3:167467071:T:TT	donor_gain	0.9900
3:167467241:C:CC	acceptor_gain	0.9900
3:167473845:CATT:C	acceptor_gain	0.9900
3:167442182:GATT:G	acceptor_gain	0.9800
3:167442183:ATT:A	acceptor_gain	0.9800
3:167449124:T:TA	donor_gain	0.9800
3:167465201:CCAA:C	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000039759 (3:167461265 C>T), RS1000087923 (3:167460817 A>T), RS1000148186 (3:167454714 C>G), RS1000212167 (3:167467680 T>C), RS1000303592 (3:167450600 A>G), RS1000443903 (3:167475678 T>C), RS1000675637 (3:167452027 T>C), RS1000871670 (3:167456409 A>G), RS1000912836 (3:167444141 G>A), RS1000983032 (3:167476898 T>A), RS1000996932 (3:167462541 G>T), RS1001015416 (3:167444856 A>C), RS1001248205 (3:167477103 T>C), RS1001261842 (3:167478139 G>A), RS1001424351 (3:167455733 C>G)

Disease associations

OMIM: gene MIM:605587 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004048_1	Fast beta electroencephalogram	5.000000e-09
GCST009391_575	Metabolite levels	7.000000e-06
GCST009391_633	Metabolite levels	3.000000e-06
GCST010135_19	Oily fish consumption	3.000000e-10
GCST010136_12	Fruit consumption	1.000000e-08
GCST010140_11	Pork consumption	3.000000e-10
GCST010142_12	Fish- and plant-related diet	1.000000e-11
GCST012489_93	Heel bone mineral density x serum urate levels interaction	8.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0021604	hypoxanthine measurement
EFO:0010503	inosine measurement
EFO:0008111	diet measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
sodium arsenite	affects methylation	1
vanadyl sulfate	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
bisphenol S	decreases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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