SERPINE2

Summary

SERPINE2 (serpin family E member 2, HGNC:8951) is a protein-coding gene on chromosome 2q36.1, encoding Glia-derived nexin (P07093). Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase.

This gene encodes a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. Thrombin, urokinase, plasmin and trypsin are among the proteases that this family member can inhibit. This gene is a susceptibility gene for chronic obstructive pulmonary disease and for emphysema. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5270 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_001136528

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8951
Approved symbol	SERPINE2
Name	serpin family E member 2
Location	2q36.1
Locus type	gene with protein product
Status	Approved
Aliases	PN1, GDN, PNI, nexin
Ensembl gene	ENSG00000135919
Ensembl biotype	protein_coding
OMIM	177010
Entrez	5270

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 35 protein_coding, 3 retained_intron

ENST00000258405, ENST00000409304, ENST00000409840, ENST00000423446, ENST00000432738, ENST00000447280, ENST00000454956, ENST00000473202, ENST00000478966, ENST00000489065, ENST00000873013, ENST00000873014, ENST00000873015, ENST00000873016, ENST00000873017, ENST00000873018, ENST00000873019, ENST00000931205, ENST00000931206, ENST00000931207, ENST00000931208, ENST00000931209, ENST00000931210, ENST00000931211, ENST00000957694, ENST00000957695, ENST00000957696, ENST00000957697, ENST00000957698, ENST00000957699, ENST00000957700, ENST00000957701, ENST00000957702, ENST00000957703, ENST00000957704, ENST00000957705, ENST00000957706, ENST00000957707

RefSeq mRNA: 3 — MANE Select: NM_001136528 NM_001136528, NM_001136530, NM_006216

CCDS: CCDS2460, CCDS46525, CCDS46526

Canonical transcript exons

ENST00000409304 — 9 exons

Exon	Start	End
ENSE00000786368	223991803	223992000
ENSE00000786369	223998115	223998342
ENSE00001698430	224039099	224039286
ENSE00002132595	223984752	223984950
ENSE00003512289	223980311	223980397
ENSE00003593798	224001642	224001922
ENSE00003651525	223977544	223977627
ENSE00003691989	223982681	223982781
ENSE00003846321	223975045	223975904

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 164.6957 / max 5773.8833, expressed in 1440 samples.

FANTOM5 promoters (30 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34230	154.4802	1436
34228	2.8165	599
34204	1.2875	387
34221	0.7512	252
34188	0.6432	244
34202	0.5771	237
34231	0.3778	225
34222	0.3351	120
34199	0.3139	137
34196	0.2947	139

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.69	gold quality
cartilage tissue	UBERON:0002418	99.59	gold quality
placenta	UBERON:0001987	99.51	gold quality
stromal cell of endometrium	CL:0002255	99.41	gold quality
ventral tegmental area	UBERON:0002691	98.81	gold quality
tibia	UBERON:0000979	98.77	gold quality
paraflocculus	UBERON:0005351	98.67	gold quality
dorsal root ganglion	UBERON:0000044	98.62	gold quality
lateral globus pallidus	UBERON:0002476	98.49	gold quality
trigeminal ganglion	UBERON:0001675	98.46	gold quality
superior vestibular nucleus	UBERON:0007227	98.42	gold quality
frontal pole	UBERON:0002795	98.29	gold quality
olfactory bulb	UBERON:0002264	98.11	gold quality
subthalamic nucleus	UBERON:0001906	98.04	gold quality
pericardium	UBERON:0002407	97.98	gold quality
cranial nerve II	UBERON:0000941	97.91	gold quality
globus pallidus	UBERON:0001875	97.91	gold quality
medulla oblongata	UBERON:0001896	97.90	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.90	gold quality
amygdala	UBERON:0001876	97.85	gold quality
nucleus accumbens	UBERON:0001882	97.84	gold quality
medial globus pallidus	UBERON:0002477	97.80	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.73	gold quality
midbrain	UBERON:0001891	97.70	gold quality
caudate nucleus	UBERON:0001873	97.69	gold quality
substantia nigra	UBERON:0002038	97.64	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.58	gold quality
middle frontal gyrus	UBERON:0002702	97.56	gold quality
putamen	UBERON:0001874	97.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.51	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	20983.84
E-MTAB-6701	yes	9236.20
E-MTAB-8142	yes	7386.37
E-MTAB-8221	yes	5117.90
E-HCAD-24	yes	3201.51
E-MTAB-9388	yes	3047.48
E-MTAB-8559	yes	2106.29
E-MTAB-7407	yes	1480.52
E-GEOD-109979	yes	1115.26
E-MTAB-10855	yes	574.50
E-MTAB-5061	yes	328.27
E-GEOD-84465	yes	23.94
E-HCAD-31	yes	23.25
E-GEOD-135922	yes	21.00
E-GEOD-81608	yes	17.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, E2F1, EGR2, EGR4, FOXO3, NR0B2, PPARG, SP1, USF1

miRNA regulators (miRDB)

44 targeting SERPINE2, 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-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3606-5P	99.31	69.67	1168

Literature-anchored findings (GeneRIF, showing 40)

• Elevated levels of GDN/PN1 and XIP mRNAs induced by Allitridi provide valuable molecular evidence for elucidating garlic’s efficacies against neurodegenerative and inflammatory diseases. (PMID:11925594)
• PN1 may play a much larger role in the modeling and remodeling of brain tissues during development and is not simply an extravasated thrombin clearance mechanism as previously suggested (PMID:12356769)
• the 4G/4G-PAI-1 genotype might be a protective factor against atherothrombotic cerebral infarction (ACI), whereas the factor V point mutation (1691G-A) and the factor VII Arg/Gln353 gene polymorphism have not proved to be risk factors for ACI (PMID:12859287)
• The pericyte expression of protease nexin 1 may provide endogenous anticoagulant activity. (PMID:16015279)
• Arg15, Phe34, Pro13, and Arg20 are important for FXIa inhibition by PN2 Kunitz protease inhibitor domain (PMID:16085935)
• SERPINE2 is a COPD-susceptibility gene and is likely influenced by gene-by-smoking interaction. (PMID:16358219)
• This study shows that syndecan-1-mediated internalization of protease nexin-1 stimulated the Ras-ERK signaling pathway. (PMID:16741952)
• Expression array analysis demonstrated association and repication of SERPINE2 as a potential COPD susceptibility gene. (PMID:16921128)
• Protease nexin-1 forms complexes with thrombomodulin and modulates its anticoagulant activity. (PMID:17379830)
• provides support for SERPINE2 as a COPD susceptibility gene (PMID:17446335)
• Co-injection of pancreatic stellate cells and tumor cells dramatically enhances the invasive potential of SERPINE2-expressing SUIT-2 cells in nude mice. (PMID:17703087)
• Macrophages and platelets are the major source of protease nexin-1 in human atherosclerotic plaque. (PMID:18617644)
• in severe COPD, SNPs in EPHX1 and SERPINE2 were associated with hypoxemia (PMID:19017876)
• Here, we report that nexin-1 inhibits trypsin-4, and forms stable complexes only with this trypsin-isoenzyme. This result suggests that nexin-1 could modulate trypsin activity in brain where both nexin-1 and trypsin-4 are expressed. (PMID:19249338)
• High affinity binding of non-proteinase-complexed PAI-1 and PN-1 occurred to all LRP1 fragments containing three CR domains (3-59 nm) and most that contain only two CR domains (PMID:19439404)
• Results suggest that PN-1 might become a prognostic marker in breast cancer. (PMID:19584287)
• Our results failed to obtain the evidence that these SNPs in SERPINE2 contributed to the chronic obstructive pulmonary disease susceptibility in the Han Chinese population (PMID:19604412)
• our results seem to discard the role of the previously described polymorphisms in SERPINE2, PPP6C and PBX3 in celiac disease susceptibility. (PMID:19626039)
• Platelet PN-1 is a key player in the thrombotic process, whose negative regulatory role has been, up to now, markedly underestimated. (PMID:19855083)
• Results suggest that the SERPINE2 gene contributes to the susceptibility to COPD. (PMID:19949669)
• SERPINE2 was identified as a possible promoter of testicular germ cell tumors lymph node metastasis. (PMID:20035713)
• SERPINE2, was previously identified as a COPD susceptibility gene in the chromosome 2q linkage region. Using independent genotyping data in 2 smaller studies in Boston and Norway the results were replicated. (PMID:20463177)
• human astrocytes express Pn-1 and astrocytic expression is regulated in a dynamic manner by injury-related factors (PMID:20623540)
• SERPINE2 was overexpressed in the ER-negative breast cancer group. (PMID:20805453)
• In cerebellum, thrombin can activate PAR-1 expression after ICH, and PN-1 appears quickly after Intracerebral hemorrhage in order to control the deleterious effect of thrombin. (PMID:20819545)
• data indicate that serpinE2 is up-regulated by oncogenic activation of Ras, BRAF and MEK1 and contributes to pro-neoplastic actions of ERK signaling in intestinal epithelial cells. (PMID:20942929)
• SERPINE2 may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers. (PMID:21067581)
• platelet PN-1 can be considered as a new important regulator of thrombolysis in vivo (PMID:21403095)
• SERPINE2 protein is highly expressed in the endometrium during the secretory phase, indicating that it may participate in tissue remodeling involved in implantation. (PMID:21426587)
• Results weakly support SERPINE2 as a Dutch hypothesis candidate gene through nominally significant associations with asthma and related traits. (PMID:21436250)
• SERPINE2 gene is a chronic obstructive pulmonary disease susceptibility gene, and block 1 of SERPINE2 appears to be the genetic variant region that affects the Han Chinese. (PMID:21611750)
• data identify the temporal and spatial SERPINE2 distribution in the human placenta and suggest its possible role in modulating tissue remodeling of extravillous trophoblasts in the placenta during pregnancy. (PMID:21806836)
• Data suggested that there was no significant association between SERPINE2 polymorphism and COPD susceptibility in the Chinese Han population. (PMID:22028159)
• The variant allele of the rs729631 SNP was found to pose over two-fold risk for overall panlobular changes and over four-fold risk for pathological panlobular changes. (PMID:22145704)
• PN-1 has direct antiangiogenic properties and is a yet-unrecognized player in the angiogenic balance (PMID:22331468)
• crystal structures of PN1 in complex with heparin and catalytically inert thrombin suggest a unique 2-step mechanism of thrombin recognition involving rapid electrostatics-driven association (PMID:22618708)
• PN1 regulates Hh signaling by decreasing protein levels of the Hh ligand Sonic (SHH) and its downstream effectors. (PMID:23041623)
• Studies suggest that protease nexin 1 as a marker of prostate cancer. (PMID:23385179)
• Endothelial protease nexin-1 is a novel regulator of A disintegrin and metalloproteinase 17 maturation and endothelial protein C receptor shedding via furin inhibition. (PMID:23661674)
• SERPINE2 and PLAU are involved in cumulus expansion and oocyte maturation. (PMID:24023701)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	serpine2	ENSDARG00000029353
mus_musculus	Serpine2	ENSMUSG00000026249
rattus_norvegicus	Serpine2	ENSRNOG00000015461

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), 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

Glia-derived nexin — P07093 (reviewed: P07093)

Alternative names: Peptidase inhibitor 7, Protease nexin 1, Protease nexin I, Serpin E2

All UniProt accessions (4): C9JN98, C9JRK5, C9K031, P07093

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase. Promotes neurite extension by inhibiting thrombin. Binds heparin.

Subcellular location. Secreted. Extracellular space.

Similarity. Belongs to the serpin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P07093-1	1	yes
P07093-2	2
P07093-3	3

RefSeq proteins (3): NP_001130000, NP_001130002, NP_006207 (=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 (50 total): strand 18, helix 15, turn 6, sequence conflict 2, glycosylation site 2, splice variant 2, sequence variant 2, signal peptide 1, chain 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4DY0	X-RAY DIFFRACTION	2.35
4DY7	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07093-F1	88.69	0.77

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): 365–366 (reactive bond)

Glycosylation sites (2): 118, 159

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-75205	Dissolution of Fibrin Clot
R-HSA-9769733	Fibrin formation
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9769743	Amplification and propagation of coagulation cascade
R-HSA-140837
R-HSA-140875

MSigDB gene sets: 504 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, LEE_SP4_THYMOCYTE, GOBP_HINDBRAIN_DEVELOPMENT, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_BEHAVIOR, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_REGULATION_OF_COAGULATION, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOCC_SECRETORY_GRANULE

GO Biological Process (30): negative regulation of cell population proliferation (GO:0008285), negative regulation of plasminogen activation (GO:0010757), negative regulation of sodium ion transport (GO:0010766), negative regulation of protein processing (GO:0010955), cerebellar granular layer morphogenesis (GO:0021683), cell differentiation (GO:0030154), protein catabolic process (GO:0030163), platelet activation (GO:0030168), negative regulation of blood coagulation (GO:0030195), negative regulation of cell growth (GO:0030308), regulation of cell migration (GO:0030334), secretion by cell (GO:0032940), secretory granule organization (GO:0033363), negative regulation of protein catabolic process (GO:0042177), mating plug formation (GO:0042628), negative regulation of proteolysis (GO:0045861), negative regulation of smoothened signaling pathway (GO:0045879), regulation of timing of cell differentiation (GO:0048505), positive regulation of astrocyte differentiation (GO:0048711), detection of mechanical stimulus involved in sensory perception (GO:0050974), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), regulation of synaptic transmission, glutamatergic (GO:0051966), long-term synaptic potentiation (GO:0060291), innervation (GO:0060384), seminal vesicle epithelium development (GO:0061108), negative regulation of platelet aggregation (GO:0090331), nervous system development (GO:0007399), blood coagulation (GO:0007596), response to wounding (GO:0009611), negative regulation of platelet activation (GO:0010544)

GO Molecular Function (6): serine-type endopeptidase inhibitor activity (GO:0004867), signaling receptor binding (GO:0005102), glycosaminoglycan binding (GO:0005539), heparin binding (GO:0008201), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), extracellular matrix (GO:0031012), platelet alpha granule (GO:0031091), neuromuscular junction (GO:0031594), extracellular vesicle (GO:1903561)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Coagulation pathway	3
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cellular process	2
blood coagulation	2
negative regulation of protein metabolic process	2
cellular anatomical structure	2
cell population proliferation	1
regulation of cell population proliferation	1
regulation of plasminogen activation	1
negative regulation of protein processing	1
plasminogen activation	1
regulation of sodium ion transport	1
sodium ion transport	1
negative regulation of monoatomic ion transport	1
protein processing	1
negative regulation of proteolysis	1
regulation of protein processing	1
negative regulation of protein maturation	1
anatomical structure morphogenesis	1
cerebellar granular layer development	1
cerebellar cortex morphogenesis	1
cellular developmental process	1
macromolecule catabolic process	1
protein metabolic process	1
cell activation	1
regulation of blood coagulation	1
negative regulation of coagulation	1
negative regulation of wound healing	1
negative regulation of hemostasis	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
cell migration	1
regulation of cell motility	1
secretion	1
export from cell	1
endomembrane system organization	1
vesicle organization	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
insemination	1

Protein interactions and networks

STRING

1944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINE2	SNX1	Q13596	922
SERPINE2	VPS29	Q9UBQ0	894
SERPINE2	SNX4	O95219	893
SERPINE2	SNX5	Q9Y5X3	879
SERPINE2	SNX2	P82862	863
SERPINE2	VPS26A	O75436	843
SERPINE2	SNX6	Q9UNH7	839
SERPINE2	SNX3	O60493	833
SERPINE2	SNX13	Q9Y5W8	812
SERPINE2	DRC4	O95995	811
SERPINE2	SNX27	Q96L92	801
SERPINE2	VTN	P01141	795
SERPINE2	DRC2	Q8IXS2	790
SERPINE2	SNX17	Q15036	785
SERPINE2	PLAU	P00749	771

IntAct

51 interactions, top by confidence:

A	B	Type	Score
SERPINE2	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
C1QTNF9B	PLOD3	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
ORF17.5	WWP2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
FURIN	ESYT2	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
RTN1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CDH23	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
KCNMB3	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
KCNE1	GPR89A	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF7	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): FAM9B (Two-hybrid), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), PLAT (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), SERPINE2 (Reconstituted Complex), SERPINE2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A090BX51, A0A0K8RCY5, A0A0K8RJ89, A0A0K8RJV9, A0A7H0DNF9, B3RFC3, E2RVI8, O73860, O75635, P01008, P01012, P01014, P05120, P07092, P07093, P07385, P0DSW3, P12388, P13909, P14754, P15059, P19104, P20961, P22777, P22922, P42926, P50449, P68565, P68566, P79335, P80034, Q06B72, Q06B74, Q06B75, Q07235, Q27085, Q27086, Q5MGH0, Q5R5A3, Q6J201

Diamond homologs: A0A090BX51, A0A0K8RCY5, A0A0K8RJ89, A0A0K8RJV9, A2I7M9, A2I7N0, A2I7N1, A2I7N2, A2I7N3, A5PJK0, A6QPQ2, A9RA96, B0CMB0, B1MTC3, B2D1U1, B2KI30, B3RFC3, B4USX2, E2RVI8, O08800, O35684, O73790, O73860, O75830, P01008, P01012, P01014, P05120, P05121, P05154, P05619, P07092, P07093, P07759, P09006, P12388, P13909, P14754, P17475, P29508

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1658 predictions. Top by Δscore:

Variant	Effect	Δscore
2:223977623:TGCAG:T	acceptor_gain	1.0000
2:223977625:CAG:C	acceptor_gain	1.0000
2:223977626:AGC:A	acceptor_loss	1.0000
2:223977627:GCTA:G	acceptor_loss	1.0000
2:223977628:C:CC	acceptor_gain	1.0000
2:223977628:C:CG	acceptor_loss	1.0000
2:223977629:T:C	acceptor_loss	1.0000
2:223982679:A:AC	donor_gain	1.0000
2:223982680:C:CC	donor_gain	1.0000
2:223984750:A:AC	donor_gain	1.0000
2:223984751:C:CT	donor_gain	1.0000
2:223991746:AAGGG:A	donor_gain	1.0000
2:223991795:GAAC:G	donor_loss	1.0000
2:223991796:AAC:A	donor_loss	1.0000
2:223991797:ACT:A	donor_loss	1.0000
2:223991798:C:CG	donor_loss	1.0000
2:223991799:TCACC:T	donor_loss	1.0000
2:223991800:CA:C	donor_loss	1.0000
2:223991801:A:AC	donor_gain	1.0000
2:223991801:A:AT	donor_loss	1.0000
2:223991802:C:CC	donor_gain	1.0000
2:223991802:CCA:C	donor_gain	1.0000
2:223991802:CCACA:C	donor_gain	1.0000
2:223998113:ACC:A	donor_gain	1.0000
2:223998114:CCC:C	donor_gain	1.0000
2:223998338:AACTC:A	acceptor_gain	1.0000
2:223998340:CTC:C	acceptor_gain	1.0000
2:223998343:C:A	acceptor_loss	1.0000
2:223998343:C:CC	acceptor_gain	1.0000
2:223998344:T:A	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000032376 (2:223987479 C>A,T), RS1000063400 (2:224034185 T>G), RS1000077032 (2:224035879 A>G), RS1000087328 (2:223996168 T>C), RS1000147637 (2:224037060 A>G), RS1000214620 (2:223991837 C>A,G), RS1000268290 (2:223992079 C>G,T), RS1000328909 (2:224025864 C>T), RS1000383832 (2:223986317 G>A), RS1000426423 (2:223976712 T>C,G), RS1000609160 (2:224018263 TC>T), RS1000632518 (2:224003275 C>G,T), RS1000649732 (2:224012240 T>C), RS1000670479 (2:223990197 C>T), RS1000730482 (2:224031481 C>A,T)

Disease associations

OMIM: gene MIM:177010 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000817_35	Height	8.000000e-12
GCST001997_1	Adverse response to chemotherapy (neutropenia/leucopenia) (5-fluorouracil)	4.000000e-06
GCST004071_2	Cerebrospinal T-tau levels	2.000000e-06
GCST004432_36	Platelet-derived growth factor BB levels	2.000000e-55
GCST004599_288	Mean platelet volume	2.000000e-10
GCST006585_400	Blood protein levels	6.000000e-246
GCST008839_510	Height	4.000000e-14
GCST009243_1	Cytokine levels	4.000000e-18
GCST009243_10	Cytokine levels	2.000000e-06
GCST009243_7	Cytokine levels	1.000000e-07
GCST009244_1	Cytokine network levels (multivariate analysis)	9.000000e-29
GCST009244_4	Cytokine network levels (multivariate analysis)	2.000000e-12
GCST009244_6	Cytokine network levels (multivariate analysis)	1.000000e-59
GCST90000584_5	Inflammatory biomarkers (multivariate analysis)	0.000000e+00
GCST90000584_6	Inflammatory biomarkers (multivariate analysis)	3.000000e-78
GCST90000584_7	Inflammatory biomarkers (multivariate analysis)	1.000000e-08
GCST90002395_360	Mean platelet volume	7.000000e-31

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement
EFO:0004750	interleukin 10 measurement
EFO:0004753	interleukin 12 measurement
EFO:0004810	interleukin-6 measurement
EFO:0008165	interferon gamma measurement
EFO:0008174	interleukin 17 measurement
EFO:0008184	interleukin 4 measurement
EFO:0008293	stromal cell-derived factor 1 alpha measurement
EFO:0004872	inflammatory biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	6
Aflatoxin B1	affects expression, increases expression, increases methylation	6
bisphenol A	increases methylation, affects expression, affects cotreatment, decreases methylation, decreases expression	4
sodium arsenite	decreases expression, increases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, affects expression, increases expression	4
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	4
Cisplatin	increases expression, affects response to substance	3
Doxorubicin	decreases expression, increases expression	3
Cyclosporine	increases expression	3
Particulate Matter	increases expression, affects cotreatment, decreases expression, increases abundance	3
perfluorooctanoic acid	increases expression	2
Air Pollutants	increases expression, increases abundance	2
Dexamethasone	decreases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	increases expression	2
Rotenone	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	increases expression	2
sotorasib	affects cotreatment, decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
carbendazim	increases expression	1
deoxynivalenol	decreases expression	1
methylselenic acid	increases expression	1
trichostatin A	affects expression	1
hydroxyhydroquinone	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1

Clinical trials (associated diseases)

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