SERPINB3

Summary

SERPINB3 (serpin family B member 3, HGNC:10569) is a protein-coding gene on chromosome 18q21.33, encoding Serpin B3 (P29508). May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells.

Enables cysteine-type endopeptidase inhibitor activity; protease binding activity; and virus receptor activity. Involved in several processes, including autocrine signaling; paracrine signaling; and regulation of protein metabolic process. Located in several cellular components, including cytoplasmic vesicle; cytosol; and extracellular exosome.

Source: NCBI Gene 6317 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total — 1 pathogenic
• MANE Select transcript: NM_006919

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10569
Approved symbol	SERPINB3
Name	serpin family B member 3
Location	18q21.33
Locus type	gene with protein product
Status	Approved
Aliases	T4-A, HsT1196
Ensembl gene	ENSG00000057149
Ensembl biotype	protein_coding
OMIM	600517
Entrez	6317

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000283752, ENST00000332821, ENST00000864638, ENST00000864639, ENST00000864640, ENST00000943132

RefSeq mRNA: 1 — MANE Select: NM_006919 NM_006919

CCDS: CCDS11987

Canonical transcript exons

ENST00000283752 — 8 exons

Exon	Start	End
ENSE00001594629	63657270	63657412
ENSE00001646020	63661846	63661893
ENSE00001736770	63656831	63656986
ENSE00001741007	63658513	63658630
ENSE00001744245	63660800	63660856
ENSE00001763141	63661052	63661242
ENSE00001779813	63659399	63659527
ENSE00001895575	63655197	63656061

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 99.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0686 / max 518.5607, expressed in 90 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172288	1.0686	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	99.79	gold quality
nasal cavity epithelium	UBERON:0005384	99.77	gold quality
nasal cavity mucosa	UBERON:0001826	99.71	gold quality
mammalian vulva	UBERON:0000997	99.62	gold quality
penis	UBERON:0000989	99.56	gold quality
cervix squamous epithelium	UBERON:0006922	99.37	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.20	gold quality
epithelium of bronchus	UBERON:0002031	98.97	gold quality
bronchus	UBERON:0002185	98.97	gold quality
cervix epithelium	UBERON:0004801	98.81	gold quality
bronchial epithelial cell	CL:0002328	98.76	gold quality
lower esophagus mucosa	UBERON:0035834	98.32	gold quality
esophagus mucosa	UBERON:0002469	98.28	gold quality
gingiva	UBERON:0001828	98.18	gold quality
esophagus squamous epithelium	UBERON:0006920	97.88	gold quality
gingival epithelium	UBERON:0001949	97.75	gold quality
squamous epithelium	UBERON:0006914	97.59	gold quality
epithelium of esophagus	UBERON:0001976	97.07	gold quality
pharyngeal mucosa	UBERON:0000355	96.55	gold quality
trachea	UBERON:0003126	96.28	gold quality
tongue squamous epithelium	UBERON:0006919	96.27	gold quality
upper leg skin	UBERON:0004262	94.71	gold quality
oral cavity	UBERON:0000167	94.70	gold quality
body of tongue	UBERON:0011876	93.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.12	gold quality
vagina	UBERON:0000996	89.18	gold quality
epithelium of nasopharynx	UBERON:0001951	88.90	gold quality
nasopharynx	UBERON:0001728	88.89	gold quality
periodontal ligament	UBERON:0008266	83.53	gold quality
tongue	UBERON:0001723	80.56	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	12896.45
E-HCAD-1	yes	3806.78
E-MTAB-10596	yes	2811.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ETV4, JUN, NR3C1, STAT1, STAT6

miRNA regulators (miRDB)

29 targeting SERPINB3, 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-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539
HSA-MIR-10A-3P	93.57	64.43	451

Literature-anchored findings (GeneRIF, showing 40)

• concentration and the positivity rate significantly elevated with esophageal squamous cell tumor progression; differences depended on tumor size, tumor depth, lymph node status, and distant metastasis (PMID:12773976)
• in the described patient groups, SCC is probably of low value for tumor diagnosis and follow-up (PMID:12820321)
• interacts with specific endogenous proteinases such as cathepsins L and L2 in physiological and pathological states of squamous epithelium (PMID:12874860)
• the inhibitory mechanism of SCCA1 is unique among the serpin superfamily (PMID:12949073)
• transfection of SCCA1 into mammalian cells (both hepatocyte-derived and of non-hepatocyte origin) results in increased HBV binding (PMID:12975381)
• Findings suggest that genetic diagnosis by RT-PCR based on SCCA mRNA expression may be clinically useful for detecting occult tumor cells in cervical lymph nodes. (PMID:14654899)
• E-cadherin mediated cell-cell adhesion maintains SCCA production through PI 3-kinase in squamous cell carcinoma. (PMID:14719077)
• SCCA variants are overexpressed in hepatocellular carcinoma independently of tumour etiology; a novel SCCA1 variant has been identified in one third of liver tumours (PMID:14970861)
• Hepatitis B virus sequence is able to induce overexpression of SCCA at the cell surface in squamous cell carcinoma. (PMID:14993646)
• Exposure of uterine cervical squamous carcinoma CaSki cells to CDDP resulted in a transient increase in SCC Ag protein and mRNA expression (PMID:15001834)
• Uteroglobin suppresses SCCA gene expression associated with airway inflammation in asthma (PMID:15677460)
• Single nucleotide polymorphism of SCCA2 indicated that this polymorphism may underlie the difference in promoter activity between SCCA1 and SCCA2. (PMID:15733534)
• the hydrophobicity of the reactive site loop of SCCA1 may play an important role in hepatitis B virus binding to cells (PMID:15902720)
• alpha-fetoprotein and SCCA yielded a correct serologic diagnosis in 90.83% of the hepatocarcinoma patients. (PMID:15906357)
• squamous cell carcinoma antigen is expressed in peripheral blood of cancer patients (PMID:16681421)
• SCC-Ag mRNA levels in the peripheral blood are the best predictive factor for recurrence in patients with esophageal squamous cell carcinoma who undergo curative resection. (PMID:16701102)
• The expression pattern of SCCA1 in esophageal dysplasia and squamous cell carcinmoma was studied. (PMID:17523076)
• Squamous cellular carcinoma immunocomplexed is increased in scleroderma patients with lung fibrosis. (PMID:18078639)
• Serum levels of MMP-9, CEA and SCC-Ag in esophageal cancer (EC) patients were statistically higher than in controls (PMID:18155162)
• Blood levels of IgG autoantibodies that bind to squamous cell carcinoma antigen proteins were significantly higher in psoriasis than healthy controls. (PMID:18385761)
• The aim of the study was to explore SCCA-1 polymorphism in patients with HCV infection as single etiologic factor and different extent of liver disease. The SCCA-PD variant was more frequently found in liver cirrhosis. (PMID:18657489)
• Activated STAT3 is a required part of the continuous activation of B3/B4 genes, which protects tumor cells from dying. (PMID:19070595)
• Elevated squamous cell carcinoma antigen is associated with hepatocellular carcinoma. (PMID:19112206)
• role in apoptosis and autoimmunity; review (PMID:19332150)
• Data show that show that SCCA-1 (B3) and SCCA-2 (B4) can bind heparin as demonstrated by affinity chromatography, native PAGE gel shifts, and intrinsic fluorescence quenching. (PMID:19959474)
• SCCA1 plays an important role in the induction of epidermal barrier disruption. SCCA1 may be a critical determinant of barrier function in the epidermis. (PMID:20089382)
• Chronically damaged hepatocytes produce SERPINB3 and TGF-beta, and the anti-protease activity of the serpin might be implicated in TGF-beta1 induction. (PMID:20212457)
• carbonyl reductase binds to SCCA1 and SCCA2 and they are co-located in the same layer of the squamous epithelium (PMID:20428762)
• SCCA, EGFR and cyclin D1 may prove to be useful tumor markers in oral squamous cell carcinoma. (PMID:20586028)
• serum squamous cell carcinoma antigen is a relatively good method for the detection of disease recurrence in patients with cervical cancer who were treated by concurrent chemoradiotherapy. (PMID:20840788)
• In conclusion, the single amino acid substitution G351Ain the SERPINB3 reactive site loop improves the functional activity of the isoform. (PMID:21383048)
• This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma. (PMID:21526154)
• SERPINB3 is over-expressed in hepatoblastoma and its expression is positively correlated with Myc expression and high tumour stage. (PMID:21737255)
• SCC, CEA, Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung, especially when they were assayed together for one patient. (PMID:22088515)
• The data strongly suggest that FTL and SCCA1 may serve as coreceptors in HBV cellular attachment and virus entry into hepatocytes. (PMID:22359459)
• Serpin B3/B4, particularly Serpin B4, appears to play an important role in aberrant epithelial proliferation. (PMID:22406480)
• Toxoplasma gondii induces SERPIN B3/B4 expression via STAT6 activation to inhibit the apoptosis of infected cells for survival of the parasites. (PMID:22451727)
• investigation of circulating levels of squamous cell carcinoma-antigen, carcinoembryonic antigen, and carbohydrate antigen 19-9 as prognostic markers in women with early stage squamous cell carcinoma of uterine cervix (PMID:22563932)
• IgM-linked SCCA isoforms circulate in patients with chronic liver disease, compared to total SCCA-IgM levels. (PMID:22808225)
• Surface localization of SERPINB3 was confirmed by confocal microscopy. SERPINB3 positivity was associated with CD27 reactivity (r = 0.98), but not to other activation molecules (PMID:22829702)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpinb3a	ENSMUSG00000044594
mus_musculus	Serpinb3d	ENSMUSG00000058017
mus_musculus	Serpinb3c	ENSMUSG00000073601
mus_musculus	Serpinb3b	ENSMUSG00000073602
rattus_norvegicus	Serpinb3a	ENSRNOG00000066913
rattus_norvegicus	Serpinb3	ENSRNOG00000070387

Paralogs (36): SERPINB1 (ENSG00000021355), 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

Serpin B3 — P29508 (reviewed: P29508)

Alternative names: Protein T4-A, Squamous cell carcinoma antigen 1

All UniProt accessions (1): P29508

UniProt curated annotations — full annotation on UniProt →

Function. May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells. Also functions as an inhibitor of UV-induced apoptosis via suppression of the activity of c-Jun NH(2)-terminal kinase (JNK1).

Subunit / interactions. Interacts with MAPK8/JNK1.

Subcellular location. Cytoplasm.

Tissue specificity. Squamous cells. Expressed in some hepatocellular carcinoma (at protein level).

Induction. Strongly up-regulated in the upper epidermis of sun-exposed skin.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P29508-1	1	yes
P29508-2	2, SCCA1b

RefSeq proteins (1): NP_008850* (*=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 16, helix 14, sequence conflict 7, turn 6, mutagenesis site 4, sequence variant 2, chain 1, site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4ZK3	X-RAY DIFFRACTION	2
4ZK0	X-RAY DIFFRACTION	2.15
2ZV6	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29508-F1	90.09	0.80

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): 354–355 (reactive bond)

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (4):

Position	Phenotype
341	loss of inhibitory activity.
352	loss of inhibitory activity.
352	loss of inhibitory activity to papain but does not decrease the suppression activity to mapk8.
354–355	loss of inhibitory activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 97 (showing top): RNGTGGGC_UNKNOWN, REACTOME_INNATE_IMMUNE_SYSTEM, JAEGER_METASTASIS_DN, GOCC_SECRETORY_GRANULE, EFC_Q6, PATIL_LIVER_CANCER, BILD_HRAS_ONCOGENIC_SIGNATURE, DAUER_STAT3_TARGETS_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, MODULE_99, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, MODULE_113, AFFAR_YY1_TARGETS_UP, MODULE_6, MODULE_207

GO Biological Process (12): positive regulation of cell population proliferation (GO:0008284), negative regulation of peptidase activity (GO:0010466), positive regulation of epithelial to mesenchymal transition (GO:0010718), positive regulation of endopeptidase activity (GO:0010950), negative regulation of endopeptidase activity (GO:0010951), positive regulation of cell migration (GO:0030335), autocrine signaling (GO:0035425), paracrine signaling (GO:0038001), negative regulation of catalytic activity (GO:0043086), negative regulation of JUN kinase activity (GO:0043508), negative regulation of proteolysis (GO:0045861), symbiont entry into host cell (GO:0046718)

GO Molecular Function (7): protease binding (GO:0002020), serine-type endopeptidase inhibitor activity (GO:0004867), cysteine-type endopeptidase inhibitor activity (GO:0004869), virus receptor activity (GO:0001618), endopeptidase inhibitor activity (GO:0004866), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), vesicle (GO:0031982), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endopeptidase activity	3
cellular anatomical structure	3
peptidase activity	2
regulation of endopeptidase activity	2
cell-cell signaling	2
endopeptidase inhibitor activity	2
cytoplasm	2
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
negative regulation of proteolysis	1
negative regulation of hydrolase activity	1
regulation of peptidase activity	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
positive regulation of peptidase activity	1
negative regulation of peptidase activity	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
catalytic activity	1
negative regulation of molecular function	1
regulation of catalytic activity	1
JUN kinase activity	1
negative regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
negative regulation of JNK cascade	1
proteolysis	1
regulation of proteolysis	1
negative regulation of protein metabolic process	1
viral life cycle	1
symbiont entry into host	1
enzyme binding	1
serine-type endopeptidase activity	1
cysteine-type endopeptidase activity	1
symbiont entry into host cell	1
exogenous protein binding	1
peptidase inhibitor activity	1

Protein interactions and networks

STRING

1192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINB3	SNX27	Q96L92	762
SERPINB3	CYTIP	O60759	742
SERPINB3	DGKZ	Q13574	663
SERPINB3	CSTA	P01040	651
SERPINB3	PLG	P00747	593
SERPINB3	CTSS	P25774	566
SERPINB3	BPIFB1	Q8TDL5	556
SERPINB3	HTR2C	P28335	545
SERPINB3	CYTH1	Q15438	510
SERPINB3	S100A7	P31151	506
SERPINB3	ING1	Q9UK53	480
SERPINB3	ERV3-1	Q14264	476
SERPINB3	ERVFRD-1	P60508	466
SERPINB3	ERVW-1	Q9UQF0	464
SERPINB3	SMC3	Q9UQE7	461

IntAct

176 interactions, top by confidence:

A	B	Type	Score
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
JADE1	KAT7	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
SERPINB3	SERPINB4	psi-mi:“MI:0914”(association)	0.620
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
SERPINB4	SERPINB3	psi-mi:“MI:0915”(physical association)	0.620
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
RBM24	PPL	psi-mi:“MI:0914”(association)	0.530
KIR3DS1	PPL	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
UCP2	CST4	psi-mi:“MI:0914”(association)	0.530
UGT1A10	A2ML1	psi-mi:“MI:0914”(association)	0.530
ACAD9	PPL	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530
DPPA4	ALOX12B	psi-mi:“MI:0914”(association)	0.530
AIRE	ALOX12B	psi-mi:“MI:0914”(association)	0.530

BioGRID (254): SERPINB3 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), HDLBP (Affinity Capture-MS), SH3GLB1 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), EIF2B1 (Co-fractionation), SERPINB3 (Co-fractionation)

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	50
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
564569	GRCh37/hg19 18q21.32-23(chr18:56905884-78014123)x1	Pathogenic

SpliceAI

770 predictions. Top by Δscore:

Variant	Effect	Δscore
18:63656057:TCAAG:T	acceptor_gain	1.0000
18:63656058:CAAG:C	acceptor_gain	1.0000
18:63656058:CAAGC:C	acceptor_gain	1.0000
18:63656059:AAG:A	acceptor_gain	1.0000
18:63656059:AAGC:A	acceptor_gain	1.0000
18:63656060:AG:A	acceptor_gain	1.0000
18:63656060:AGCT:A	acceptor_gain	1.0000
18:63656061:GC:G	acceptor_loss	1.0000
18:63656061:GCTA:G	acceptor_gain	1.0000
18:63656062:C:A	acceptor_gain	1.0000
18:63656062:C:CC	acceptor_gain	1.0000
18:63656062:CT:C	acceptor_loss	1.0000
18:63656063:T:A	acceptor_gain	1.0000
18:63656064:A:AC	acceptor_gain	1.0000
18:63656064:A:C	acceptor_gain	1.0000
18:63656067:CAAA:C	acceptor_gain	1.0000
18:63656070:A:AC	acceptor_gain	1.0000
18:63656070:A:C	acceptor_gain	1.0000
18:63656825:TCTTA:T	donor_loss	1.0000
18:63656826:CTTA:C	donor_loss	1.0000
18:63656827:TTACC:T	donor_loss	1.0000
18:63656828:TA:T	donor_loss	1.0000
18:63656830:C:CT	donor_loss	1.0000
18:63656830:CCTT:C	donor_gain	1.0000
18:63656927:C:CT	acceptor_gain	1.0000
18:63656928:A:T	acceptor_gain	1.0000
18:63656935:C:CT	acceptor_gain	1.0000
18:63656985:TT:T	acceptor_gain	1.0000
18:63657017:C:CT	acceptor_gain	1.0000
18:63657018:A:T	acceptor_gain	1.0000

AlphaMissense

2607 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:63657326:A:G	W186R	0.991
18:63657326:A:T	W186R	0.991
18:63655723:G:C	F369L	0.990
18:63655723:G:T	F369L	0.990
18:63655725:A:G	F369L	0.990
18:63657312:A:C	F190L	0.990
18:63657312:A:T	F190L	0.990
18:63657314:A:G	F190L	0.990
18:63657282:A:C	F200L	0.989
18:63657282:A:T	F200L	0.989
18:63657284:A:G	F200L	0.989
18:63661118:G:C	S33R	0.989
18:63661118:G:T	S33R	0.989
18:63661120:T:G	S33R	0.989
18:63657324:C:A	W186C	0.988
18:63657324:C:G	W186C	0.988
18:63655735:A:C	C365W	0.979
18:63657347:C:G	A179P	0.977
18:63661084:C:G	A45P	0.977
18:63661173:A:G	L15P	0.977
18:63657348:G:C	N178K	0.976
18:63657348:G:T	N178K	0.976
18:63655737:A:G	C365R	0.975
18:63656904:A:G	L232P	0.974
18:63657313:A:G	F190S	0.974
18:63658574:A:C	F136L	0.974
18:63658574:A:T	F136L	0.974
18:63658576:A:G	F136L	0.974
18:63655741:G:C	F363L	0.973
18:63655741:G:T	F363L	0.973

dbSNP variants (sampled 300 via entrez): RS1000864610 (18:63662721 C>T), RS1000939413 (18:63662470 A>G), RS1001149611 (18:63658240 G>C), RS1001283829 (18:63655996 T>G), RS1001518757 (18:63658433 G>C,T), RS1001817493 (18:63660204 C>G), RS1001871764 (18:63663591 T>C), RS1004633937 (18:63655738 A>G), RS1005105661 (18:63659997 G>A,C), RS1005766339 (18:63661730 G>A), RS1006070461 (18:63661023 C>A), RS1006741772 (18:63663271 T>C), RS1008048028 (18:63658665 A>T), RS1008303359 (18:63660524 A>T), RS1008429286 (18:63656310 T>A,C)

Disease associations

OMIM: gene MIM:600517 | 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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	5
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
Calcitriol	decreases expression, increases reaction	2
Nickel	increases expression	2
Sodium Dodecyl Sulfate	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Particulate Matter	increases expression, affects cotreatment, increases abundance	2
urushiol	increases expression	1
propionaldehyde	increases expression	1
geraniol	increases expression	1
lead acetate	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
cinnamaldehyde	increases expression	1
nickel sulfate	decreases expression	1
resorcinol	increases expression	1
seocalcitol	decreases expression	1
deguelin	decreases secretion	1
monomethylarsonous acid	decreases expression	1
ortho-topolin riboside	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Endosulfan	increases expression	1
Estradiol	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1UE	HyCyte THP-1 KO-hSERPINB3	Cancer cell line	Male

Clinical trials (associated diseases)

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