SERPINE3

Summary

SERPINE3 (serpin family E member 3, HGNC:24774) is a protein-coding gene on chromosome 13q14.3, encoding Serpin E3 (A8MV23). Probable serine protease inhibitor.

Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 647174 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• MANE Select transcript: NM_001386375

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24774
Approved symbol	SERPINE3
Name	serpin family E member 3
Location	13q14.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000253309
Ensembl biotype	protein_coding
OMIM	620989
Entrez	647174

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000400389, ENST00000419898, ENST00000521255, ENST00000524365, ENST00000681248

RefSeq mRNA: 2 — MANE Select: NM_001386375 NM_001101320, NM_001386375

CCDS: CCDS53870, CCDS91808

Canonical transcript exons

ENST00000681248 — 10 exons

Exon	Start	End
ENSE00001760571	51340784	51340861
ENSE00002094172	51344252	51344485
ENSE00002114368	51355043	51355143
ENSE00002122873	51364239	51364735
ENSE00002124203	51361278	51361364
ENSE00002124436	51347025	51347234
ENSE00002126153	51361810	51361893
ENSE00002131400	51348213	51348411
ENSE00002140155	51341075	51341347
ENSE00003912342	51339691	51339743

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 89.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0559 / max 1220.1635, expressed in 58 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135192	0.9310	43
135191	0.0859	13
135190	0.0161	5
135194	0.0092	1
207036	0.0077	3
135193	0.0061	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.08	gold quality
cerebellar hemisphere	UBERON:0002245	62.80	gold quality
cerebellum	UBERON:0002037	62.76	gold quality
cerebellar cortex	UBERON:0002129	62.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.62	gold quality
corpus callosum	UBERON:0002336	61.51	gold quality
left uterine tube	UBERON:0001303	60.60	gold quality
calcaneal tendon	UBERON:0003701	59.64	gold quality
right lobe of liver	UBERON:0001114	59.11	gold quality
body of pancreas	UBERON:0001150	58.89	gold quality
liver	UBERON:0002107	57.01	gold quality
primary visual cortex	UBERON:0002436	56.99	gold quality
omental fat pad	UBERON:0010414	56.51	gold quality
tibial nerve	UBERON:0001323	55.93	gold quality
popliteal artery	UBERON:0002250	55.93	gold quality
tibial artery	UBERON:0007610	55.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	55.39	gold quality
pancreas	UBERON:0001264	54.85	gold quality
body of uterus	UBERON:0009853	53.59	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	53.31	gold quality
right frontal lobe	UBERON:0002810	53.29	gold quality
cortical plate	UBERON:0005343	53.02	silver quality
metanephros cortex	UBERON:0010533	52.95	gold quality
adipose tissue	UBERON:0001013	52.81	gold quality
fallopian tube	UBERON:0003889	52.58	gold quality
putamen	UBERON:0001874	52.56	gold quality
adrenal tissue	UBERON:0018303	52.53	gold quality
apex of heart	UBERON:0002098	52.45	gold quality
brain	UBERON:0000955	52.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting SERPINE3, 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-498-3P	99.91	71.27	1114
HSA-MIR-9898	99.00	67.89	500
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-6894-5P	98.70	63.78	809

Literature-anchored findings (GeneRIF, showing 1)

• Vision-related convergent gene losses reveal SERPINE3’s unknown role in the eye. (PMID:35727138)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	serpine3	ENSDARG00000057108
mus_musculus	Serpine3	ENSMUSG00000091155
rattus_norvegicus	Serpine3	ENSRNOG00000009814

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), 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), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Serpin E3 — A8MV23 (reviewed: A8MV23)

All UniProt accessions (2): A8MV23, E5RG55

UniProt curated annotations — full annotation on UniProt →

Function. Probable serine protease inhibitor.

Subcellular location. Secreted.

Similarity. Belongs to the serpin family.

Isoforms (2)

UniProt ID	Names	Canonical?
A8MV23-1	1	yes
A8MV23-2	2

RefSeq proteins (2): NP_001094790, NP_001373304* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR031172	Serpin_E3	Family
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (9 total): compositionally biased region 2, signal peptide 1, chain 1, region of interest 1, site 1, glycosylation site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MV23-F1	79.41	0.57

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): 369–370 (reactive bond)

Glycosylation sites (1): 46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): chr13q14, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, ZNF22_TARGET_GENES, MIR6894_5P, NABA_ECM_REGULATORS, DESCARTES_MAIN_FETAL_RETINAL_PIGMENT_CELLS, DESCARTES_FETAL_CEREBRUM_MEGAKARYOCYTES, FOURATI_BLOOD_TWINRIX_AGE_25_83YO_RESPONDERS_VS_POOR_RESPONDERS_0DY_UP, GOMF_MOLECULAR_FUNCTION_INHIBITOR_ACTIVITY, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN, GOMF_PEPTIDASE_INHIBITOR_ACTIVITY

GO Biological Process (0):

GO Molecular Function (2): serine-type endopeptidase inhibitor activity (GO:0004867), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), 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
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINE3	SPACA9	Q96E40	558
SERPINE3	ZNF706	Q9Y5V0	518
SERPINE3	WDFY2	Q96P53	510
SERPINE3	ANKRD29	Q8N6D5	500
SERPINE3	INTS6	Q9UL03	490
SERPINE3	PPP1R36	Q96LQ0	449
SERPINE3	ADAMTS15	Q8TE58	429
SERPINE3	FAM124A	Q86V42	423
SERPINE3	ABHD14A	Q9BUJ0	422
SERPINE3	HABP2	Q14520	413
SERPINE3	CPLX4	Q7Z7G2	389
SERPINE3	PRSS55	Q6UWB4	381
SERPINE3	PLEKHG3	A1L390	367
SERPINE3	SLC50A1	Q9BRV3	367
SERPINE3	RNF122	Q9H9V4	354

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2I7N3, A6QPQ2, A6QQ92, A8MV23, B0UYL8, B2D1U1, E1BF81, P01017, P01019, P05154, P05155, P05545, P07758, P07759, P08185, P08697, P09006, P20757, P22323, P23035, P23775, P26595, P28800, P29621, P29622, P36955, P49920, P50448, P50451, P97298, Q00896, Q00898, Q03734, Q09055, Q5I2A0, Q5R9E3, Q5RDA8, Q60396, Q61247, Q63556

Diamond homologs: A6QQ92, A8MV23, B0UYL8, P01008, P01013, P01014, P05121, P05619, P07092, P07093, P09005, P0DSW3, P0DSW4, P13909, P14369, P30740, P32261, P50449, P50452, P79335, P80229, Q07235, Q1JPB0, Q43492, Q4G075, Q5BIR5, Q5I0S8, Q5R5A3, Q5SV42, Q8VHP7, Q9D154, Q9GP13, O73860, P20842, P20961, Q27085, Q9SIR9, E2RVI8, O08800, O35684

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1719 predictions. Top by Δscore:

Variant	Effect	Δscore
13:51341131:T:A	acceptor_gain	1.0000
13:51341134:T:A	acceptor_gain	1.0000
13:51341349:T:A	donor_loss	1.0000
13:51361269:T:A	acceptor_gain	1.0000
13:51361271:T:TA	acceptor_gain	1.0000
13:51361272:G:A	acceptor_gain	1.0000
13:51361273:GTTA:G	acceptor_loss	1.0000
13:51361274:TTAG:T	acceptor_loss	1.0000
13:51361276:A:AG	acceptor_gain	1.0000
13:51361276:A:G	acceptor_loss	1.0000
13:51361277:G:GG	acceptor_gain	1.0000
13:51361362:CAGGT:C	donor_loss	1.0000
13:51361363:AGGT:A	donor_loss	1.0000
13:51361364:GGTA:G	donor_loss	1.0000
13:51361365:G:C	donor_loss	1.0000
13:51361366:T:A	donor_loss	1.0000
13:51361809:GCTCT:G	acceptor_gain	1.0000
13:51339740:GTCT:G	donor_gain	0.9900
13:51339744:G:GG	donor_gain	0.9900
13:51340757:ATAAT:A	acceptor_gain	0.9900
13:51341126:A:AG	acceptor_gain	0.9900
13:51341127:C:G	acceptor_gain	0.9900
13:51344250:A:AG	acceptor_gain	0.9900
13:51344251:G:GA	acceptor_gain	0.9900
13:51348212:GGTCA:G	acceptor_gain	0.9900
13:51361276:AG:A	acceptor_gain	0.9900
13:51361277:GG:G	acceptor_gain	0.9900
13:51361277:GGCC:G	acceptor_gain	0.9900
13:51361277:GGCCA:G	acceptor_gain	0.9900
13:51361365:G:GG	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000526505 (13:51359654 A>G), RS1000643609 (13:51341645 G>A), RS1001172741 (13:51353532 C>A), RS1001255695 (13:51362483 C>T), RS1001353740 (13:51360574 T>C,G), RS1001491418 (13:51353240 C>T), RS1001632691 (13:51344178 A>G), RS1001728196 (13:51362226 T>C), RS1001849248 (13:51360900 A>T), RS1002105701 (13:51342049 C>T), RS1002453244 (13:51356108 C>T), RS1002484212 (13:51355703 T>C), RS1002500560 (13:51354607 T>A,G), RS1002618948 (13:51347644 A>C), RS1002819334 (13:51344143 C>A,G,T)

Disease associations

OMIM: gene MIM:620989 | 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
GCST002616_10	Mitochondrial DNA levels	6.000000e-06
GCST009411_17	Optic disc area	9.000000e-08
GCST009416_6	Optic nerve head parameters (multi-trait analysis)	2.000000e-08
GCST010002_187	Refractive error	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement
EFO:0006939	cup-to-disc ratio measurement

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
aristolochic acid I	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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