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SERPINB12

gene
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Summary

SERPINB12 (serpin family B member 12, HGNC:14220) is a protein-coding gene on chromosome 18q21.33, encoding Serpin B12 (Q96P63). Inhibits trypsin and plasmin, but not thrombin, coagulation factor Xa, or urokinase-type plasminogen activator.

Enables serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of protein catabolic process. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Located in collagen-containing extracellular matrix.

Source: NCBI Gene 89777 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 73 total
  • Druggable target: yes
  • MANE Select transcript: NM_001307928

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:14220
Approved symbolSERPINB12
Nameserpin family B member 12
Location18q21.33
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000166634
Ensembl biotypeprotein_coding
OMIM615662
Entrez89777

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000269491, ENST00000382768, ENST00000680447

RefSeq mRNA: 2 — MANE Select: NM_001307928 NM_001307928, NM_080474

CCDS: CCDS11984, CCDS77194

Canonical transcript exons

ENST00000382768 — 8 exons

ExonStartEnd
ENSE000010118296356108563561202
ENSE000010118306355957863559718
ENSE000011049096355614263556327
ENSE000011049126356544563565612
ENSE000011049136356397863564120
ENSE000014933086355835263558486
ENSE000039134486354236963542492
ENSE000039147226356660763569329

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 87.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2077 / max 235.3133, expressed in 16 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
1705800.11509
1705790.063010
1705810.02963

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
skin of legUBERON:000151187.84gold quality
skin of abdomenUBERON:000141687.81gold quality
zone of skinUBERON:000001485.62gold quality
penisUBERON:000098979.94gold quality
mammalian vulvaUBERON:000099775.12gold quality
upper leg skinUBERON:000426268.92gold quality
vaginaUBERON:000099666.88gold quality
lower esophagus mucosaUBERON:003583466.04gold quality
endothelial cellCL:000011564.71gold quality
esophagus mucosaUBERON:000246963.43gold quality
epithelium of nasopharynxUBERON:000195159.16gold quality
skin of hipUBERON:000155458.58gold quality
mammary ductUBERON:000176555.56gold quality
parotid glandUBERON:000183152.73gold quality
cardia of stomachUBERON:000116248.71gold quality
ectocervixUBERON:001224948.64gold quality
tracheaUBERON:000312648.07gold quality
tonsilUBERON:000237247.25gold quality
middle temporal gyrusUBERON:000277146.16gold quality
esophagusUBERON:000104346.06gold quality
uterine cervixUBERON:000000245.14gold quality
gingivaUBERON:000182844.78gold quality
inferior vagus X ganglionUBERON:000536343.70gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451143.37gold quality
vastus lateralisUBERON:000137943.13gold quality
quadriceps femorisUBERON:000137743.05gold quality
renal medullaUBERON:000036243.04gold quality
gingival epitheliumUBERON:000194942.70gold quality
secondary oocyteCL:000065542.57gold quality
subthalamic nucleusUBERON:000190642.35gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes3.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting SERPINB12, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3646100.0073.565283
HSA-MIR-186-5P99.9970.833707
HSA-MIR-513B-5P99.9969.962150
HSA-MIR-19A-3P99.9875.332762
HSA-MIR-19B-3P99.9875.442754
HSA-MIR-4650-5P99.9864.69999
HSA-MIR-806899.9873.852376
HSA-MIR-477599.9875.006394
HSA-MIR-7111-5P99.9768.482062
HSA-MIR-302E99.9670.742669
HSA-MIR-426799.9666.532368
HSA-MIR-4725-3P99.9669.532520
HSA-MIR-6780B-5P99.9669.602562
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-6755-5P99.9565.59464
HSA-MIR-651-3P99.9473.485177
HSA-MIR-806399.9169.763146
HSA-MIR-568099.9169.833421
HSA-MIR-302A-3P99.8971.231777
HSA-MIR-302B-3P99.8971.231777
HSA-MIR-302C-3P99.8971.201778
HSA-MIR-302D-3P99.8971.251777
HSA-MIR-6783-3P99.8967.922059
HSA-MIR-427199.8868.322244
HSA-MIR-605-3P99.8869.221833
HSA-MIR-548AR-3P99.8571.263889
HSA-MIR-520E-3P99.8470.551698
HSA-MIR-373-3P99.8470.681668
HSA-MIR-469899.8471.414303
HSA-MIR-372-3P99.8370.581691

Literature-anchored findings (GeneRIF, showing 6)

  • data suggest that SERPINB12, like some other intracellular serpins, may play a vital role in barrier function by providing protection of epithelial cells. (PMID:26220980)
  • SERPINB12 formed a covalent complex with GZMA and inhibited the enzyme with typical serpin slow-binding kinetics. SERPINB12 also inhibited Hepsin. SERPINB12 may function as an endogenous inhibitor of these peptidases. (PMID:26497600)
  • SLFN12 regulates human enterocytic differentiation by a pathway involving SERPB12, the deubiquitylases, and Cdx2. (PMID:30045019)
  • HSLFN12’s partner hSerpinB12 may contribute to heterochromatin formation. (PMID:31026779)
  • SERPINB12 as a possible marker of steroid dependency in children with eosinophilic esophagitis: A pilot study. (PMID:31653522)
  • Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC. (PMID:38504347)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusSerpinb12ENSMUSG00000059956
rattus_norvegicusSerpinb12ENSRNOG00000002602

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), 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 B12 — Q96P63 (reviewed: Q96P63)

All UniProt accessions (1): Q96P63

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits trypsin and plasmin, but not thrombin, coagulation factor Xa, or urokinase-type plasminogen activator. May play a role in cell differentiation.

Subunit / interactions. Interacts with SLFN12; as part of a pathway regulating cell differentiation. May interact with USP14.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in many tissues, including brain, bone marrow, lymph node, heart, lung, liver, pancreas, testis, ovary, and intestine.

Similarity. Belongs to the serpin family. Ov-serpin subfamily.

Isoforms (2)

UniProt IDNamesCanonical?
Q96P63-11yes
Q96P63-22

RefSeq proteins (2): NP_001294857, NP_536722 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000215Serpin_famFamily
IPR023795Serpin_CSConserved_site
IPR023796Serpin_domDomain
IPR036186Serpin_sfHomologous_superfamily
IPR042178Serpin_sf_1Homologous_superfamily
IPR042185Serpin_sf_2Homologous_superfamily

Pfam: PF00079

UniProt features (7 total): sequence variant 3, chain 1, region of interest 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96P63-F189.290.79

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): 370–371 (reactive bond)

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

IDPathway
R-HSA-6798695Neutrophil degranulation
R-HSA-168249Innate Immune System
R-HSA-168256Immune System

MSigDB gene sets: 70 (showing top): GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, GOCC_SECRETORY_VESICLE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_CORNIFIED_ENVELOPE

GO Biological Process (2): hematopoietic progenitor cell differentiation (GO:0002244), negative regulation of protein catabolic process (GO:0042177)

GO Molecular Function (3): serine-type endopeptidase inhibitor activity (GO:0004867), enzyme binding (GO:0019899), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (6): cornified envelope (GO:0001533), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), ficolin-1-rich granule membrane (GO:0101003)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
Innate Immune System1
Immune System1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
hemopoiesis1
cell differentiation1
negative regulation of catabolic process1
protein catabolic process1
regulation of protein catabolic process1
negative regulation of protein metabolic process1
serine-type endopeptidase activity1
endopeptidase inhibitor activity1
protein binding1
enzyme inhibitor activity1
peptidase activity1
peptidase regulator activity1
plasma membrane1
intracellular anatomical structure1
cellular anatomical structure1
membrane1
cell periphery1
external encapsulating structure1
secretory granule membrane1
tertiary granule1
ficolin-1-rich granule1

Protein interactions and networks

STRING

678 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
SERPINB12CASP14P31944519
SERPINB12SLFN12Q8IYM2506
SERPINB12HPNP05981494
SERPINB12SPRR4Q96PI1474
SERPINB12PNLIPRP3Q17RR3465
SERPINB12KPRPQ5T749460
SERPINB12SBSNQ6UWP8460
SERPINB12HEPACAM2A8MVW5454
SERPINB12LCE1FQ5T754433
SERPINB12KLK6Q92876426
SERPINB12HEPACAMQ14CZ8424
SERPINB12LCE6AA0A183404
SERPINB12CPLX4Q7Z7G2392
SERPINB12KRT4P19013392
SERPINB12KRT77Q7Z794381

IntAct

56 interactions, top by confidence:

ABTypeScore
CFTRESYT2psi-mi:“MI:0914”(association)0.710
IFT88IFT56psi-mi:“MI:0914”(association)0.640
NCBP2KPNA3psi-mi:“MI:0914”(association)0.640
POLR2LRCCD1psi-mi:“MI:0914”(association)0.640
KPNB1POM121Cpsi-mi:“MI:0914”(association)0.530
DDX21MED19psi-mi:“MI:2364”(proximity)0.480
Pds5apsi-mi:“MI:0915”(physical association)0.400
Nrip3SERPINB12psi-mi:“MI:0915”(physical association)0.400
Cdc23ANAPC15psi-mi:“MI:0914”(association)0.350
THOC5MYO1Gpsi-mi:“MI:0914”(association)0.350
BAXBDP1psi-mi:“MI:0914”(association)0.350
LLGL1ALDH1B1psi-mi:“MI:0914”(association)0.350
COQ2SNRPGP15psi-mi:“MI:0914”(association)0.350
METTL14HMGB1P1psi-mi:“MI:0914”(association)0.350
CUL2ANXA2P2psi-mi:“MI:0914”(association)0.350
LRRK2psi-mi:“MI:0914”(association)0.350
RAD51CSTApsi-mi:“MI:0914”(association)0.350
UTYKMT2Dpsi-mi:“MI:0914”(association)0.350
Ppsi-mi:“MI:0914”(association)0.350
NCBP1IGF2BP3psi-mi:“MI:0914”(association)0.350
reppsi-mi:“MI:0914”(association)0.350
RYBPFAM186Apsi-mi:“MI:0914”(association)0.350
DYRK1ATEX13Dpsi-mi:“MI:0914”(association)0.350
CACNA1CIGLL5psi-mi:“MI:0914”(association)0.350
DRG1RPS3Apsi-mi:“MI:0914”(association)0.350
RBM8AMCRIP1psi-mi:“MI:0914”(association)0.350

BioGRID (130): SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS), SERPINB12 (Affinity Capture-MS)

ESM2 similar proteins: A0A090BX51, A2I7M9, A2I7N0, A2I7N2, A5PJK0, A9RA96, B0CMB0, B1MTB7, B1MTC3, B2KI30, B3RFC3, B4USX2, E2RVI8, O08800, O73790, O73860, O75635, P01012, P01013, P01014, P05120, P05544, P09006, P12388, P19104, P29508, P29524, P36952, P48594, P48595, P70124, P70458, P70564, Q03044, Q52L45, Q5I0S8, Q5M8J5, Q5SV42, Q6GLQ1, Q6V115

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Transport of Mature mRNA derived from an Intron-Containing Transcript513.6×5e-03
Regulation of expression of SLITs and ROBOs67.4×9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance71
Likely benign2
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

895 predictions. Top by Δscore:

VariantEffectΔscore
18:63558482:AGCAG:Adonor_loss1.0000
18:63558483:GCAG:Gdonor_gain1.0000
18:63558485:AGGT:Adonor_loss1.0000
18:63558486:GG:Gdonor_loss1.0000
18:63558487:GTG:Gdonor_loss1.0000
18:63559573:CTTAG:Cacceptor_loss1.0000
18:63559574:TTAG:Tacceptor_loss1.0000
18:63559575:TA:Tacceptor_loss1.0000
18:63559576:A:Tacceptor_loss1.0000
18:63559576:AGGCT:Aacceptor_gain1.0000
18:63559577:G:GCacceptor_loss1.0000
18:63559577:GGCT:Gacceptor_gain1.0000
18:63559577:GGCTG:Gacceptor_gain1.0000
18:63561075:A:AGacceptor_gain1.0000
18:63561075:AAT:Aacceptor_gain1.0000
18:63566605:A:AGacceptor_gain1.0000
18:63566605:AGCTT:Aacceptor_gain1.0000
18:63566606:G:GCacceptor_gain1.0000
18:63566606:GC:Gacceptor_gain1.0000
18:63566606:GCTT:Gacceptor_gain1.0000
18:63566606:GCTTG:Gacceptor_gain1.0000
18:63558347:TGCAG:Tacceptor_loss0.9900
18:63558348:GCAG:Gacceptor_loss0.9900
18:63558349:CA:Cacceptor_loss0.9900
18:63558351:G:GAacceptor_loss0.9900
18:63558501:T:TAdonor_gain0.9900
18:63558502:A:AAdonor_gain0.9900
18:63559572:CCTTA:Cacceptor_loss0.9900
18:63559576:A:AGacceptor_gain0.9900
18:63559577:G:GGacceptor_gain0.9900

AlphaMissense

2857 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
18:63564064:T:AW197R0.988
18:63564064:T:CW197R0.988
18:63564066:G:CW197C0.985
18:63564066:G:TW197C0.985
18:63566943:T:CF384L0.985
18:63566945:T:AF384L0.985
18:63566945:T:GF384L0.985
18:63564106:T:CF211L0.984
18:63564108:C:AF211L0.984
18:63564108:C:GF211L0.984
18:63556259:A:CS34R0.981
18:63556261:C:AS34R0.981
18:63556261:C:GS34R0.981
18:63566925:T:CF378L0.978
18:63566927:T:AF378L0.978
18:63566927:T:GF378L0.978
18:63556295:G:CA46P0.970
18:63561177:C:AN159K0.967
18:63561177:C:GN159K0.967
18:63564076:T:CF201L0.966
18:63564078:T:AF201L0.966
18:63564078:T:GF201L0.966
18:63566782:T:CL330P0.966
18:63561139:T:CF147L0.965
18:63561141:C:AF147L0.965
18:63561141:C:GF147L0.965
18:63556293:G:AG45D0.964
18:63564029:T:CL185P0.963
18:63566760:T:CF323L0.963
18:63566762:T:AF323L0.963

dbSNP variants (sampled 300 via entrez): RS1000003312 (18:63562896 T>C), RS1000069636 (18:63523331 G>A), RS1000097662 (18:63536939 A>G), RS1000169752 (18:63538241 C>T), RS1000178370 (18:63568397 A>G), RS1000185175 (18:63520462 T>A,C), RS1000269678 (18:63549287 C>G,T), RS1000371114 (18:63547672 T>A), RS1000374600 (18:63534839 A>G), RS1000449531 (18:63536488 A>G), RS1000517364 (18:63567072 G>A), RS1000522270 (18:63519177 G>A,C), RS1000569707 (18:63565730 G>A,T), RS1000618751 (18:63565454 A>G), RS1000640741 (18:63533393 T>G)

Disease associations

OMIM: gene MIM:615662 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725093 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Benzo(a)pyreneincreases methylation, increases mutagenesis2
sodium arseniteincreases expression1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression1
CGP 52608affects binding, increases reaction1
Resveratrolaffects cotreatment, decreases expression1
Acetaminophenincreases expression1
Cadmiumdecreases expression, increases abundance1
Lipopolysaccharidesaffects response to substance, increases expression1
Plant Extractsaffects cotreatment, decreases expression1
Cadmium Chloridedecreases expression, increases abundance1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5697774BindingInhibition of SERPINB12 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysisInhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 78

This page pulls from 78 datasets indexed by BioBTree:

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