SERPINB9

Summary

SERPINB9 (serpin family B member 9, HGNC:8955) is a protein-coding gene on chromosome 6p25.2, encoding Serpin B9 (P50453). Granzyme B inhibitor.

This gene encodes a member of the serine protease inhibitor family which are also known as serpins. The encoded protein belongs to a subfamily of intracellular serpins. This protein inhibits the activity of the effector molecule granzyme B. Overexpression of this protein may prevent cytotoxic T-lymphocytes from eliminating certain tumor cells. A pseudogene of this gene is found on chromosome 6.

Source: NCBI Gene 5272 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_004155

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8955
Approved symbol	SERPINB9
Name	serpin family B member 9
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	CAP3
Ensembl gene	ENSG00000170542
Ensembl biotype	protein_coding
OMIM	601799
Entrez	5272

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000380698, ENST00000718363, ENST00000893932, ENST00000893933, ENST00000918069, ENST00000918070, ENST00000918071, ENST00000970292

RefSeq mRNA: 1 — MANE Select: NM_004155 NM_004155

CCDS: CCDS4478

Canonical transcript exons

ENST00000380698 — 7 exons

Exon	Start	End
ENSE00001161143	2891833	2891988
ENSE00001161151	2893411	2893553
ENSE00001161158	2895391	2895508
ENSE00001161167	2896053	2896190
ENSE00001485983	2900444	2900621
ENSE00001485991	2903201	2903309
ENSE00004034883	2887270	2890570

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 94.85.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9314 / max 488.4674, expressed in 681 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71423	1.3226	466
71418	0.8762	246
71416	0.6428	232
71422	0.0675	25
71417	0.0224	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	94.85	gold quality
mononuclear cell	CL:0000842	93.29	gold quality
monocyte	CL:0000576	93.28	gold quality
leukocyte	CL:0000738	93.22	gold quality
germinal epithelium of ovary	UBERON:0001304	92.45	gold quality
vermiform appendix	UBERON:0001154	92.34	gold quality
lymph node	UBERON:0000029	91.98	gold quality
placenta	UBERON:0001987	91.67	gold quality
tibial nerve	UBERON:0001323	90.80	gold quality
blood	UBERON:0000178	89.33	gold quality
granulocyte	CL:0000094	88.92	gold quality
caecum	UBERON:0001153	87.44	gold quality
spleen	UBERON:0002106	87.43	gold quality
oocyte	CL:0000023	86.44	gold quality
endothelial cell	CL:0000115	85.50	silver quality
sural nerve	UBERON:0015488	84.74	gold quality
renal glomerulus	UBERON:0000074	84.67	gold quality
lower esophagus mucosa	UBERON:0035834	84.67	gold quality
tonsil	UBERON:0002372	84.63	gold quality
metanephric glomerulus	UBERON:0004736	84.56	gold quality
palpebral conjunctiva	UBERON:0001812	84.21	gold quality
superficial temporal artery	UBERON:0001614	84.16	gold quality
upper lobe of left lung	UBERON:0008952	84.14	gold quality
upper lobe of lung	UBERON:0008948	83.54	gold quality
secondary oocyte	CL:0000655	83.46	gold quality
right lung	UBERON:0002167	83.09	gold quality
adrenal tissue	UBERON:0018303	82.87	gold quality
bone marrow cell	CL:0002092	82.47	gold quality
adult organism	UBERON:0007023	82.36	gold quality
buccal mucosa cell	CL:0002336	82.26	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	1382.71
E-GEOD-100618	yes	337.96
E-MTAB-8142	yes	101.24
E-GEOD-84465	yes	37.32
E-MTAB-9388	yes	8.11
E-MTAB-5061	yes	5.98
E-GEOD-106540	no	531.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

136 targeting SERPINB9, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 39)

• Expression levels of apoptosis-related proteins caspase 3, Bcl-2, and PI9 predict clinical outcome in anaplastic large cell lymphoma. (PMID:12036886)
• The presence and subcellular localization of proteinase inhibitor 9 in leukocytes and dendritic cells are consistent with a protective role against ectopic or misdirected granzyme B during an immune response. (PMID:12517944)
• a high expression of PI-9 by tubular epithelial cells can serve as one of the factors protecting renal allografts from rejection in spite of the presence of inflammatory cell infiltrates. (PMID:15458434)
• proteinase inhibitor 9 was effectively hydrolyzed and inactivated by human granzyme M, raising the possibility that this orphan granzyme bypasses proteinase inhibitor 9 inhibition of granzyme B (PMID:15494398)
• Since PI-9 considerably alters GrzB and killer cell sensitivity, it may strongly influence the efficacy of GvL(graft-versus-leukemia) effects (PMID:15531453)
• Over expression of SERPINB9 is associated with metastatic melanoma (PMID:16144945)
• Soluble SERPINB9 circulates in blood and increases on primary Cytomegalovirus infection in post renal transplantation patients (PMID:16267761)
• Estrogen induction of PI-9 may reduce the ability of cytolytic lymphocytes-mediated immune surveillance to destroy newly transformed cells (PMID:16306080)
• up-regulated expression of PI-9 in gestational trophoblastic diseases contributes to disease pathogenesis via immune evasion (PMID:16310039)
• loss of PI9 expression in tumor cells may reflect some mechanism associated with progression (PMID:17077322)
• PI9 inhibited apoptotic death by directly interacting with the intermediate active forms of caspase-8 and -10. This indicates that PI9 can regulate pro-apoptotic apical caspases. (PMID:17479112)
• The data suggest that PI-9 is tightly linked to maturation and may allow dendritic cells to exert their function in a potentially hostile environment. (PMID:18191723)
• A significant population consumes levels of genistein in soy products that may be high enough to induce PI-9, perhaps potentiating the survival of some preexisting breast cancers by enabling them to evade immunosurveillance. (PMID:18669594)
• upregulated expression of PI-9 in NSCLC cells may serve to protect them from apoptosis induced by GrB (PMID:19956856)
• Reduced proteinase inhibitor 9 expression in human vascular smooth muscle cells is associated with atherosclerotic disease progression. (PMID:21296596)
• constitutive expression of serine protease inhibitor 9 (PI-9) on human peripheral blood-and bone marrow-derived mesenchymal stem cells is a major defense mechanism against granzyme B-mediated destruction by NK cells (PMID:21795594)
• Inhibition of Granzyme B by PI-9 protects prostate cancer cells from apoptosis. (PMID:21919028)
• PI-9 induction within human mononuclear phagocytes by virulent Mycobacterium tuberculosis serves to protect these primary targets of infection from elimination by apoptosis and thereby promotes intracellular survival of the organism. (PMID:22090449)
• SerpinB9 expression in human renal tubular epithelial cells is induced by triggering of the viral dsRNA sensors TLR3, MDA5 and RIG-I during subclinical rejection. (PMID:22167597)
• lung cancer cells utilise their increased PI-9 expression to protect from granzyme B-mediated cytotoxicity as an immune evasion mechanism (PMID:22387007)
• Suppression of granzyme B initiated apoptosis in protease inhibitor-9-expressing leukemia cells. (PMID:23892923)
• Increased intracellular PI-9 activity in mononuclear phagocytes from HIV-infected patients contributes to successful intracellular infection by virulent Mycobacterium tuberculosis. (PMID:24445365)
• The GrB-Sb9 nexus may therefore represent an additional mechanism of limiting lymphocyte lifespan and populations. (PMID:24488096)
• We filtered four OSCC genes including SERPINB9, SERPINE2, GAK, and HSP90B1 through the gene global prioritization score (P < 0.005). (PMID:26318431)
• Data suggest that reactive oxygen species (ROS) generated within cytotoxic lymphocytes by receptor stimulation are required for lysosomal permeabilization and release of GzmB (granzyme B) into the cytosol and for inactivation of serpin B9. (PMID:26670609)
• 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 the serine protease inhibitor B9 (serpinB9) mediated caspase-1 inhibition regulates IL-1beta release in monocytes. (PMID:26992230)
• 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)
• Treatment with estrogens further increased PI-9 level while decreased that of ERalpha66 isoform thus excluding the involvement of this receptor isoform in the event. Moreover, our studies also provided evidence that tertiary tumorspheres express elevated levels of CXCR4 and phospho-p38, suggesting that the high PI-9 content might be ascribed to the activation of the proliferative CXCR4/phospho-p38 axis. (PMID:27121069)
• It was concluded that disturbed regulation of serpinB9 in circulating T cells represents a novel risk factor for post-transplant Cutaneous squamous cell carcinoma in kidney transplant recipients. (PMID:31059128)
• Telomere length correlates with subtelomeric DNA methylation in long-term mindfulness practitioners. (PMID:32165663)
• Proteomics-Based Approach Reveals the Involvement of SERPINB9 in Recurrent and Relapsed Multiple Myeloma. (PMID:33650432)
• Identification of CD56(dim) subpopulation marked with high expression of GZMB/PRF1/PI-9 in CD56(+) interferon-alpha-induced dendritic cells. (PMID:33662167)
• Decreased GZMB, NRP1, ITPR1, and SERPINB9 Transcripts Lead to Reduced Regulatory T Cells Suppressive Capacity in Generalized Vitiligo Patients. (PMID:36157881)
• SERPINB9 is commonly amplified and high expression in cancer cells correlates with poor immune checkpoint blockade response. (PMID:36465485)
• Serpin B9 controls tumor cell killing by CAR T cells. (PMID:36931661)
• Overexpression of SerpinB9 in non-seminomatous germ cell tumors. (PMID:37991604)
• Mass Spectrometry-Based Proteomics Identifies Serpin B9 as a Key Protein in Promoting Bone Metastases in Lung Cancer. (PMID:38226993)
• The expression analysis of SerpinB9 in hepatoblastoma microenvironment. (PMID:38347163)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpinb9b	ENSMUSG00000021403
mus_musculus	Serpinb9c	ENSMUSG00000021404
mus_musculus	Serpinb9f	ENSMUSG00000038327
mus_musculus	Serpinb9	ENSMUSG00000045827
mus_musculus	Serpinb9d	ENSMUSG00000054266
mus_musculus	Serpinb9g	ENSMUSG00000057726
mus_musculus	Serpinb9e	ENSMUSG00000062342
mus_musculus	Serpinb9h	ENSMUSG00000071452
rattus_norvegicus	Serpinb9d	ENSRNOG00000022139
rattus_norvegicus	Serpinb9	ENSRNOG00000033772
rattus_norvegicus	Serpinb9b	ENSRNOG00000048576

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), 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 B9 — P50453 (reviewed: P50453)

Alternative names: Cytoplasmic antiproteinase 3, Peptidase inhibitor 9

All UniProt accessions (2): P50453, A0A024QZT4

UniProt curated annotations — full annotation on UniProt →

Function. Granzyme B inhibitor.

Subcellular location. Cytoplasm.

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

RefSeq proteins (1): NP_004146* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR000240	Serpin_B9/Maspin	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 (37 total): strand 15, helix 12, turn 7, chain 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8ZCR	X-RAY DIFFRACTION	1.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50453-F1	91.74	0.84

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): 340–341 (reactive bond)

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 361 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_NEGATIVE_REGULATION_OF_NATURAL_KILLER_CELL_MEDIATED_IMMUNITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOLDRATH_ANTIGEN_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, chr6p25, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GERY_CEBP_TARGETS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, FOSTER_TOLERANT_MACROPHAGE_DN, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS

GO Biological Process (6): mast cell mediated immunity (GO:0002448), immune response (GO:0006955), protection from natural killer cell mediated cytotoxicity (GO:0042270), negative regulation of apoptotic process (GO:0043066), cellular response to estrogen stimulus (GO:0071391), negative regulation of endopeptidase activity (GO:0010951)

GO Molecular Function (5): protease binding (GO:0002020), serine-type endopeptidase inhibitor activity (GO:0004867), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	2
cytoplasm	2
myeloid leukocyte mediated immunity	1
immune system process	1
response to stimulus	1
negative regulation of natural killer cell mediated cytotoxicity	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cellular response to hormone stimulus	1
response to estrogen	1
endopeptidase activity	1
negative regulation of peptidase activity	1
regulation of endopeptidase activity	1
enzyme binding	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
cysteine-type endopeptidase regulator activity involved in apoptotic process	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
external encapsulating structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

752 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINB9	GZMB	P10144	941
SERPINB9	CASP1	P29466	709
SERPINB9	PIGM	Q9H3S5	664
SERPINB9	PRF1	P14222	651
SERPINB9	ULBP3	Q9BZM4	455
SERPINB9	RNH1	P13489	427
SERPINB9	SPINK9	Q5DT21	418
SERPINB9	TPBG	Q13641	416
SERPINB9	ALPG	P10696	391
SERPINB9	CRISP3	P54108	386
SERPINB9	PI3	P19957	384
SERPINB9	BPIFB1	Q8TDL5	384
SERPINB9	NFKB2	Q00653	384
SERPINB9	EPHA7	Q15375	383
SERPINB9	UPK1B	O75841	380

IntAct

54 interactions, top by confidence:

A	B	Type	Score
SERPINB9	TRAF5	psi-mi:“MI:0915”(physical association)	0.720
TRAF5	SERPINB9	psi-mi:“MI:0915”(physical association)	0.720
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
SERPINB9	ST3GAL3	psi-mi:“MI:0915”(physical association)	0.500
rep	SERPINB9	psi-mi:“MI:0915”(physical association)	0.490
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.350
PRKCE	PRPSAP2	psi-mi:“MI:0914”(association)	0.350
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
SERPINB9	PPIAL4C	psi-mi:“MI:0914”(association)	0.350
FAM24B	SHTN1	psi-mi:“MI:0914”(association)	0.350
RCL1	APBB1	psi-mi:“MI:0914”(association)	0.350
TIMD4	SEMG1	psi-mi:“MI:0914”(association)	0.350
ACTRT1	CCT6A	psi-mi:“MI:0914”(association)	0.350
IKBIP	SERPINB9	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
CPSF6	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
ILF3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
U2AF1	MED19	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SERPINB9	TRAF5	psi-mi:“MI:0915”(physical association)	0.000
SERPINB9		psi-mi:“MI:0915”(physical association)	0.000
SERPINB9	BRD7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (56): TRAF5 (Two-hybrid), CASP1 (Reconstituted Complex), CASP4 (Reconstituted Complex), SERPINB9 (Affinity Capture-MS), SERPINB9 (Affinity Capture-MS), CASP8 (Affinity Capture-Western), CASP10 (Affinity Capture-Western), SERPINB9 (Affinity Capture-MS), SERPINB9 (Two-hybrid), ECH1 (Two-hybrid), GBP2 (Two-hybrid), GDF9 (Two-hybrid), PLEKHM1 (Two-hybrid), C14orf1 (Two-hybrid), COPS6 (Two-hybrid)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1468 predictions. Top by Δscore:

Variant	Effect	Δscore
6:2891827:TCTTA:T	donor_loss	1.0000
6:2891828:CTTA:C	donor_loss	1.0000
6:2891829:TTAC:T	donor_loss	1.0000
6:2891830:TA:T	donor_loss	1.0000
6:2891831:A:AC	donor_gain	1.0000
6:2891831:A:AG	donor_loss	1.0000
6:2891832:C:CC	donor_gain	1.0000
6:2891832:CCGTG:C	donor_gain	1.0000
6:2891986:CTC:C	acceptor_gain	1.0000
6:2891989:CT:C	acceptor_loss	1.0000
6:2891990:T:A	acceptor_loss	1.0000
6:2893434:C:A	donor_gain	1.0000
6:2895376:A:C	donor_gain	1.0000
6:2895388:GAC:G	donor_loss	1.0000
6:2895390:CC:C	donor_loss	1.0000
6:2895506:CGT:C	acceptor_gain	1.0000
6:2895509:C:CC	acceptor_gain	1.0000
6:2896046:AACTT:A	donor_loss	1.0000
6:2896048:CT:C	donor_loss	1.0000
6:2896049:TTA:T	donor_loss	1.0000
6:2896050:TACTG:T	donor_loss	1.0000
6:2896051:A:AC	donor_gain	1.0000
6:2896051:A:T	donor_loss	1.0000
6:2896052:C:CG	donor_gain	1.0000
6:2896052:CT:C	donor_gain	1.0000
6:2900438:GCTTA:G	donor_loss	1.0000
6:2900439:CTTAC:C	donor_loss	1.0000
6:2900440:TTA:T	donor_loss	1.0000
6:2900441:TA:T	donor_loss	1.0000
6:2900442:A:AG	donor_loss	1.0000

AlphaMissense

2486 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:2893423:A:C	F185L	0.989
6:2893423:A:T	F185L	0.989
6:2893425:A:G	F185L	0.989
6:2893467:A:G	W171R	0.987
6:2893467:A:T	W171R	0.987
6:2890229:G:C	F355L	0.986
6:2890229:G:T	F355L	0.986
6:2890231:A:G	F355L	0.986
6:2893453:A:C	F175L	0.986
6:2893453:A:T	F175L	0.986
6:2893455:A:G	F175L	0.986
6:2890247:G:C	F349L	0.977
6:2890247:G:T	F349L	0.977
6:2890249:A:G	F349L	0.977
6:2893465:C:A	W171C	0.977
6:2893465:C:G	W171C	0.977
6:2893424:A:G	F185S	0.970
6:2896080:A:C	F93L	0.970
6:2896080:A:T	F93L	0.970
6:2896082:A:G	F93L	0.970
6:2900510:G:C	S34R	0.966
6:2900510:G:T	S34R	0.966
6:2900512:T:G	S34R	0.966
6:2895503:A:C	F104L	0.959
6:2895503:A:T	F104L	0.959
6:2895505:A:G	F104L	0.959
6:2890187:G:C	F369L	0.958
6:2890187:G:T	F369L	0.958
6:2890189:A:G	F369L	0.958
6:2893466:C:G	W171S	0.956

dbSNP variants (sampled 300 via entrez): RS1000215878 (6:2898712 G>A), RS1000283336 (6:2889893 G>A), RS1000451620 (6:2902055 T>A), RS1000500820 (6:2896332 A>G), RS1000502128 (6:2901935 C>T), RS1000548267 (6:2887180 A>T), RS1000697814 (6:2886861 G>A), RS1000725060 (6:2892113 A>C), RS1000732860 (6:2895183 G>A,C), RS1001458819 (6:2889583 T>C), RS1001570067 (6:2898201 G>T), RS1001722507 (6:2901628 C>G), RS1001905400 (6:2899004 A>T), RS1002104739 (6:2898786 C>T), RS1002215871 (6:2901383 C>G)

Disease associations

OMIM: gene MIM:601799 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004785_23	Vitiligo	3.000000e-08
GCST011217_5	Left ventricular global circumferential strain	5.000000e-09
GCST90002400_660	Plateletcrit	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression	8
Estradiol	affects binding, decreases reaction, increases activity, increases expression, increases reaction (+2 more)	6
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Tretinoin	decreases expression, increases expression	4
moxestrol	increases expression, increases reaction, decreases reaction, affects binding	3
trichostatin A	affects cotreatment, increases expression	3
Acetaminophen	increases expression	3
methylmercuric chloride	decreases expression, increases expression	2
afimoxifene	increases expression, increases reaction	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
belinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Fulvestrant	decreases reaction, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Lipopolysaccharides	increases expression, decreases reaction	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Rifampin	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Raloxifene Hydrochloride	increases expression, affects binding, decreases reaction	2
bisphenol F	increases expression	1
dicrotophos	increases expression	1
4-oxoretinoic acid	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1QH	Abcam K-562 SERPINB9 KO	Cancer cell line	Female
CVCL_D2M3	Abcam Raji SERPINB9 KO	Cancer cell line	Male
CVCL_WQ51	Abcam Jurkat SERPINB9 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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