SERPINB1

Summary

SERPINB1 (serpin family B member 1, HGNC:3311) is a protein-coding gene on chromosome 6p25.2, encoding Leukocyte elastase inhibitor (P30740). Neutrophil serine protease inhibitor that plays an essential role in the regulation of the innate immune response, inflammation and cellular homeostasis.

The protein encoded by this gene is a member of the serpin family of proteinase inhibitors. Members of this family maintain homeostasis by neutralizing overexpressed proteinase activity through their function as suicide substrates. This protein inhibits the neutrophil-derived proteinases neutrophil elastase, cathepsin G, and proteinase-3 and thus protects tissues from damage at inflammatory sites. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1992 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 79 total
• Druggable target: yes
• MANE Select transcript: NM_030666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3311
Approved symbol	SERPINB1
Name	serpin family B member 1
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	EI, PI2, LEI, MNEI
Ensembl gene	ENSG00000021355
Ensembl biotype	protein_coding
OMIM	130135
Entrez	1992

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000380739, ENST00000460260, ENST00000468511, ENST00000476896, ENST00000490094, ENST00000878906, ENST00000878907, ENST00000878908, ENST00000878909, ENST00000878910, ENST00000878911, ENST00000878912, ENST00000878913, ENST00000878914, ENST00000878915, ENST00000915893, ENST00000952269, ENST00000952270

RefSeq mRNA: 1 — MANE Select: NM_030666 NM_030666

CCDS: CCDS4477

Canonical transcript exons

ENST00000380739 — 7 exons

Exon	Start	End
ENSE00001486077	2832332	2834012
ENSE00001943348	2841812	2841863
ENSE00003472533	2836108	2836250
ENSE00003474766	2840419	2840594
ENSE00003477365	2838549	2838686
ENSE00003561760	2837882	2837999
ENSE00003693768	2835856	2836023

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 99.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 115.2351 / max 5914.4736, expressed in 1785 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71381	102.6108	1765
71384	9.8704	1651
71382	1.4239	741
71383	1.2135	787
71380	0.0607	21
71379	0.0557	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	99.83	gold quality
tongue squamous epithelium	UBERON:0006919	99.54	gold quality
oral cavity	UBERON:0000167	99.50	gold quality
pharyngeal mucosa	UBERON:0000355	99.50	gold quality
epithelium of esophagus	UBERON:0001976	99.41	gold quality
esophagus mucosa	UBERON:0002469	99.37	gold quality
lower esophagus mucosa	UBERON:0035834	99.23	gold quality
bone marrow	UBERON:0002371	99.00	gold quality
monocyte	CL:0000576	98.99	gold quality
palpebral conjunctiva	UBERON:0001812	98.90	gold quality
body of pancreas	UBERON:0001150	98.87	gold quality
mononuclear cell	CL:0000842	98.85	gold quality
leukocyte	CL:0000738	98.82	gold quality
jejunal mucosa	UBERON:0000399	98.62	gold quality
trabecular bone tissue	UBERON:0002483	98.49	gold quality
bone marrow cell	CL:0002092	98.48	gold quality
squamous epithelium	UBERON:0006914	98.46	gold quality
cervix squamous epithelium	UBERON:0006922	98.26	gold quality
duodenum	UBERON:0002114	98.25	gold quality
pancreas	UBERON:0001264	98.14	gold quality
blood	UBERON:0000178	98.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.12	gold quality
cervix epithelium	UBERON:0004801	98.06	gold quality
rectum	UBERON:0001052	98.05	gold quality
oviduct epithelium	UBERON:0004804	97.97	gold quality
granulocyte	CL:0000094	97.75	gold quality
epithelial cell of pancreas	CL:0000083	97.70	gold quality
tonsil	UBERON:0002372	97.68	gold quality
calcaneal tendon	UBERON:0003701	97.68	gold quality
gall bladder	UBERON:0002110	97.47	gold quality

Single-cell (SCXA)

Detected in 25 experiment(s), a significant marker in 22.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	4953.75
E-CURD-114	yes	1428.48
E-CURD-77	yes	1424.03
E-CURD-122	yes	1277.03
E-CURD-120	yes	1013.67
E-HCAD-6	yes	875.43
E-MTAB-9067	yes	664.22
E-GEOD-130473	yes	580.53
E-HCAD-8	yes	558.37
E-HCAD-1	yes	225.34
E-MTAB-8142	yes	88.62
E-HCAD-4	yes	87.46
E-HCAD-10	yes	26.73
E-GEOD-81547	yes	20.40
E-CURD-112	yes	19.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB1, NFKB, NFKBIB, RELA, SP1, SPI1

miRNA regulators (miRDB)

63 targeting SERPINB1, 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-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248

Literature-anchored findings (GeneRIF, showing 24)

• M/NEI is a dual specificity inhibitor with two adjacent reactive sites that support rapid efficient inhibitory reactions with cellular proteases, including the three neutrophil granule proteases. (PMID:11747453)
• The findings define an innate role for SerpinB1 in cystic fibrosis airways. (PMID:20817705)
• serpinB1 sustains a healthy neutrophil reserve that is required in acute immune responses. (PMID:21248149)
• These results suggest that serpin B1 may be a novel marker of active ulcerative colitis and may play an important role in the pathogenesis of inflammatory bowel disease. (PMID:22421620)
• In the resting state during human neutrophil extracellar trap generation, SerpinB1 is exclusively in the cytoplasm, consistent with the current understanding of clade B serpins, and it may migrate and regulate events in the cell nucleus. (PMID:23002442)
• Upon reactive center loop cleavage at Phe-343,SERPINB1 covalently complexes with GzmH. SERPINB1 overexpression suppresses GzmH- or LAK cell-mediated cytotoxicity. Crystal structures show possible conformational changes in GzmH for the suicide inhibition. (PMID:23269243)
• Apoptosis-inducing factor and leukocyte elastase inhibitor derived DNase II interact and can cooperate to induce cell death. (PMID:23673989)
• Decreased expression of SERPINB1 correlates with tumor invasion and poor prognosis in hepatocellular carcinoma. (PMID:24105272)
• is not expressed in neutrophils of both sulfur mustard-exposed and chronic obstructive pulmonary disease patients (PMID:24852194)
• Data suggest that serine protease inhibitor (SERPIN) B1 negatively regulates glioma cell migration and invasion probably by abrogating the expression of matrix metalloproteinase-2 and the activation of focal adhesion kinase. (PMID:24968089)
• Data show that high serpin B1 protein (SERPINB1) gene expression was associated with favorable tumor response and prolonged survival under cisplatin-based chemotherapy. (PMID:26799424)
• Pediatric CNS-PNETs evade immune recognition by downregulating cell surface MHC-I and CD1d expression. Intriguingly, expression of SERPINB9, SERPINB1, and SERPINB4 is acquired during tumorigenesis in 29%, 29%, and 57% of the tumors (PMID:26963506)
• Data show that oropharyngeal squamous cell carcinomas (OPSCCs) express granzyme inhibitors SERPINB1, SERPINB4 and SERPINB9 for cytotoxicity and the expression was not different between human papillomavirus (HPV)-positive and HPV-negative tumors. (PMID:26993499)
• a relatively low Serpinb1a protein threshold in neutrophils that is required for sustained survival (PMID:27107834)
• SERPINB1 expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• SERPINB1 decreased inflammation, ameliorated oxidative stress in the lung, and attenuated acute lung injury in rats with orthotopic autologous liver transplantation by activating HO-1 and it does so through STAT3 (PMID:28427999)
• The expression of SERPINB1 was approximately 2-fold higher in apical periodontitis. SERPINB1 expression was noted in neutrophils and epithelial cells. (PMID:28673495)
• This study demonstrated that female-specific role for SERPINB1 in amyloidosis. (PMID:29967939)
• Analysis of The Cancer Genome Atlas and pyrosequencing demonstrate hypermethylation of the SERPINB1 promoter in prostate cancer compared with normal tissue, and the extent of promoter methylation negatively correlates with SERPINB1 mRNA expression. (PMID:30610107)
• Results indicate that serpin family B member 1 (SERPINB1) acts as a vital gatekeeper of inflammation by restraining neutrophil serine proteases and inflammatory caspases in a genetically and functionally separable manner. (PMID:30692621)
• A striking decrease in the expression of SERPINB1 gene, which encodes a critical component of neutrophil survival, was detected in Cohen syndrome neutrophils. (PMID:30843084)
• A Novel SERPINB1 Single-Nucleotide Polymorphism Associated With Glycemic Control and beta-Cell Function in Egyptian Type 2 Diabetic Patients. (PMID:32903749)
• SERPINB1 overexpression protects myocardial damage induced by acute myocardial infarction through AMPK/mTOR pathway. (PMID:35291946)
• A proteomic analysis of NETosis in trauma: Emergence of serpinB1 as a key player. (PMID:36730076)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	serpinb1	ENSDARG00000055416
danio_rerio	serpinb1l2	ENSDARG00000070396
mus_musculus	Serpinb1a	ENSMUSG00000044734
mus_musculus	Serpinb1b	ENSMUSG00000051029
mus_musculus	Serpinb1c	ENSMUSG00000079049
rattus_norvegicus	Serpinb1a	ENSRNOG00000016581
rattus_norvegicus	Serpinb1b	ENSRNOG00000034229

Paralogs (36): 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), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Leukocyte elastase inhibitor — P30740 (reviewed: P30740)

Alternative names: Monocyte/neutrophil elastase inhibitor, Peptidase inhibitor 2, Serpin B1

All UniProt accessions (2): P30740, V9HWH1

UniProt curated annotations — full annotation on UniProt →

Function. Neutrophil serine protease inhibitor that plays an essential role in the regulation of the innate immune response, inflammation and cellular homeostasis. Acts primarily to protect the cell from proteases released in the cytoplasm during stress or infection. These proteases are important in killing microbes but when released from granules, these potent enzymes also destroy host proteins and contribute to mortality. Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3. Also acts as a potent intracellular inhibitor of GZMH by directly blocking its proteolytic activity. During inflammation, limits the activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation. When secreted, promotes the proliferation of beta-cells via its protease inhibitory function.

Subunit / interactions. Monomer. Interacts (via C-terminus) with CASP1; CASP4 (via CARD domain) and CASP5; these interactions regulate the activity of inflammatory caspases. Interacts with PRTN3. Interacts with GZMH.

Subcellular location. Secreted. Cytoplasm. Cytolytic granule. Early endosome.

Tissue specificity. In human bone marrow, present in all CD45+ populations. Expression levels are highest in the neutrophil lineage, intermediate in monocytic, and lowest in lymphocytic lineage. Within the neutrophil lineage, expression is highest in promyelocytes.

Domain organisation. Reactive bond 1 is specific for reaction with chymotrypsin-like protease such as cathepsin G, chymotrypsin, chymase or granzyme H, while reactive bond 2 is specific for reaction with elastase-like protease such as neutrophil elastase, proteinase-3, pancreatic elastase or PSA.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P30740-1	1	yes
P30740-2	2

RefSeq proteins (1): NP_109591* (*=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 (53 total): strand 18, helix 12, turn 6, sequence conflict 5, modified residue 4, mutagenesis site 2, site 2, chain 1, region of interest 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4GA7	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30740-F1	93.06	0.90

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 (2): 343–344 (reactive bond 1); 344–345 (reactive bond 2)

Post-translational modifications (4): 1, 137, 177, 300

Mutagenesis-validated functional residues (2):

Position	Phenotype
343	loss of proteinase-3-binding activity but caspase-binding activity remains unaffected; in association with a-344.
344	loss of proteinase-3-binding activity but caspase-binding activity remains unaffected; in association with a-343.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9948001	CASP4 inflammasome assembly

MSigDB gene sets: 364 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, CLAUS_PGR_POSITIVE_MENINGIOMA_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOCC_SECRETORY_GRANULE, MODULE_45, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_16, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, GOBP_INTERLEUKIN_1_PRODUCTION, ONDER_CDH1_TARGETS_3_DN

GO Biological Process (5): negative regulation of endopeptidase activity (GO:0010951), negative regulation of cell migration (GO:0030336), negative regulation of interleukin-1 beta production (GO:0032691), type B pancreatic cell proliferation (GO:0044342), regulation of protein metabolic process (GO:0051246)

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

GO Cellular Component (12): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), early endosome (GO:0005769), membrane (GO:0016020), extracellular matrix (GO:0031012), secretory granule lumen (GO:0034774), cytoplasmic ribonucleoprotein granule (GO:0036464), cytolytic granule (GO:0044194), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Non-canonical inflammasome activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endopeptidase activity	1
negative regulation of peptidase activity	1
regulation of endopeptidase activity	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
epithelial cell proliferation	1
protein metabolic process	1
regulation of macromolecule metabolic process	1
regulation of primary metabolic process	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
binding	1
endosome	1
external encapsulating structure	1
secretory granule	1
cytoplasmic vesicle lumen	1
cytoplasm	1
ribonucleoprotein granule	1
lysosome	1
extracellular vesicle	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINB1	ELANE	P08246	963
SERPINB1	CTSG	P08311	798
SERPINB1	LOXL1	Q08397	790
SERPINB1	MPO	P05164	685
SERPINB1	ELN	P15502	679
SERPINB1	CTRB2	Q6GPI1	655
SERPINB1	CTRB1	P17538	655
SERPINB1	FBLN5	Q9UBX5	614
SERPINB1	F13A1	P00488	601
SERPINB1	PRTN3	P15637	585
SERPINB1	A2M	P01023	562
SERPINB1	CELA1	Q9UNI1	517
SERPINB1	AKT1	P31749	516
SERPINB1	PI3	P19957	513
SERPINB1	SLPI	P03973	512

IntAct

63 interactions, top by confidence:

A	B	Type	Score
PSMD10	PSMD11	psi-mi:“MI:0914”(association)	0.800
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
SOX2	PDLIM1	psi-mi:“MI:0914”(association)	0.530
UQCRH	DCTN6	psi-mi:“MI:0914”(association)	0.530
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
TAS2R41	YKT6	psi-mi:“MI:0914”(association)	0.530
GTF2B	CST4	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
ZIC1	IMPA2	psi-mi:“MI:0914”(association)	0.350
IQCF1	TBC1D4	psi-mi:“MI:0914”(association)	0.350
NFYA	NME2P1	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
PRKCE	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
TIFAB	DDX3X	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
FAM24B	SHTN1	psi-mi:“MI:0914”(association)	0.350
KLHL11	PIPSL	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
SRRT	A2ML1	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (93): SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), ITPA (Co-fractionation), TES (Co-fractionation), TRAPPC4 (Co-fractionation), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS)

ESM2 similar proteins: O00394, O02739, O08800, O54757, O54758, O54759, O54760, O54761, O54762, O54763, P01009, P01010, P05619, P07758, P12725, P17475, P22324, P22325, P22599, P23035, P29508, P30740, P34955, P35237, P38029, P48594, P50447, P50452, P50453, P80229, P97277, Q00896, Q00897, Q00898, Q09055, Q1JPB0, Q4G075, Q4R3G2, Q52L45, Q5BIR5

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

976 predictions. Top by Δscore:

Variant	Effect	Δscore
6:2834019:T:TC	acceptor_gain	1.0000
6:2835852:ATACC:A	donor_loss	1.0000
6:2835853:TA:T	donor_loss	1.0000
6:2835854:A:AC	donor_gain	1.0000
6:2835854:A:AT	donor_loss	1.0000
6:2835855:C:A	donor_loss	1.0000
6:2835855:C:CC	donor_gain	1.0000
6:2835855:CCTT:C	donor_gain	1.0000
6:2836020:CTTT:C	acceptor_gain	1.0000
6:2836021:TTT:T	acceptor_gain	1.0000
6:2836024:C:CC	acceptor_gain	1.0000
6:2836030:A:T	acceptor_gain	1.0000
6:2836103:CTCA:C	donor_loss	1.0000
6:2836105:CAC:C	donor_loss	1.0000
6:2836106:ACCTT:A	donor_loss	1.0000
6:2836107:C:CA	donor_loss	1.0000
6:2836246:TTTTC:T	acceptor_gain	1.0000
6:2836247:TTTC:T	acceptor_gain	1.0000
6:2836247:TTTCC:T	acceptor_loss	1.0000
6:2836248:TTC:T	acceptor_gain	1.0000
6:2836249:TC:T	acceptor_gain	1.0000
6:2836249:TCCTA:T	acceptor_loss	1.0000
6:2836250:CC:C	acceptor_gain	1.0000
6:2836251:C:CC	acceptor_gain	1.0000
6:2836251:C:T	acceptor_gain	1.0000
6:2837879:CACCT:C	donor_loss	1.0000
6:2837880:ACC:A	donor_loss	1.0000
6:2837881:C:CA	donor_loss	1.0000
6:2837881:CCTT:C	donor_gain	1.0000
6:2837918:T:TA	donor_gain	1.0000

AlphaMissense

2524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:2836164:A:G	W171R	0.994
6:2836164:A:T	W171R	0.994
6:2836162:C:A	W171C	0.993
6:2836162:C:G	W171C	0.993
6:2836120:G:C	F185L	0.992
6:2836120:G:T	F185L	0.992
6:2836122:A:G	F185L	0.992
6:2836150:G:C	F175L	0.992
6:2836150:G:T	F175L	0.992
6:2836152:A:G	F175L	0.992
6:2833674:G:C	F358L	0.990
6:2833674:G:T	F358L	0.990
6:2833676:A:G	F358L	0.990
6:2840485:G:C	S34R	0.988
6:2840485:G:T	S34R	0.988
6:2840487:T:G	S34R	0.988
6:2836185:C:G	A164P	0.987
6:2833751:C:G	A333P	0.986
6:2836121:A:G	F185S	0.986
6:2837994:G:C	F104L	0.985
6:2837994:G:T	F104L	0.985
6:2837996:A:G	F104L	0.985
6:2835896:A:G	L232P	0.984
6:2836151:A:G	F175S	0.984
6:2837911:A:T	I132K	0.984
6:2833632:G:C	F372L	0.983
6:2833632:G:T	F372L	0.983
6:2833634:A:G	F372L	0.983
6:2833687:G:T	A354D	0.983
6:2836163:C:G	W171S	0.983

dbSNP variants (sampled 300 via entrez): RS1001110752 (6:2838259 C>A), RS1001172880 (6:2840334 G>A,C,T), RS1001318836 (6:2832021 G>A,C), RS1001436206 (6:2839895 G>A,T), RS1001906980 (6:2837773 G>A,C,T), RS1002138604 (6:2833543 C>T), RS1002574562 (6:2834664 G>A), RS1003108073 (6:2841586 C>G), RS1003194151 (6:2840826 AGGGT>A), RS1003294219 (6:2836415 T>C), RS1004072624 (6:2838134 A>G), RS1004140562 (6:2836773 T>C), RS1004759321 (6:2835594 C>G,T), RS1004808485 (6:2835239 G>A), RS1004957977 (6:2841781 CCCGCGCCA>C)

Disease associations

OMIM: gene MIM:130135 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004069_1	Cerebrospinal fluid AB1-42 levels	2.000000e-08
GCST009298_1	BMI at 5 years old	7.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066509 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.25	Kd	56.13	nM	CHEMBL5653589
7.25	ED50	56.13	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149378: Binding affinity to human SERPINB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0561	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects localization, affects cotreatment, increases expression	8
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic Trioxide	affects cotreatment, increases expression	4
Calcitriol	increases expression, increases reaction	4
methylmercuric chloride	decreases expression	3
Benzo(a)pyrene	increases methylation, decreases expression, increases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Valproic Acid	affects cotreatment, decreases expression, affects expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Air Pollutants	increases abundance, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Potassium Dichromate	decreases expression, increases expression	2
Quercetin	increases expression, decreases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
dicrotophos	decreases expression	1
dexamethasone 21-phosphate	affects localization, increases activity, increases cleavage	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
beta-lapachone	increases expression	1
nickel chloride	decreases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
quinoline	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652420	Binding	Binding affinity to human SERPINB1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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