SERPINA9

Summary

SERPINA9 (serpin family A member 9, HGNC:15995) is a protein-coding gene on chromosome 14q32.13, encoding Serpin A9 (Q86WD7). Protease inhibitor that inhibits trypsin and trypsin-like serine proteases (in vitro).

Enables serine-type endopeptidase inhibitor activity. Predicted to be located in cytoplasm; extracellular region; and membrane. Predicted to be active in extracellular space.

Source: NCBI Gene 327657 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 103 total
• MANE Select transcript: NM_175739

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15995
Approved symbol	SERPINA9
Name	serpin family A member 9
Location	14q32.13
Locus type	gene with protein product
Status	Approved
Aliases	SERPINA11b, GCET1
Ensembl gene	ENSG00000170054
Ensembl biotype	protein_coding
OMIM	615677
Entrez	327657

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000298845, ENST00000337425, ENST00000380365, ENST00000424550, ENST00000448305, ENST00000538527, ENST00000539349, ENST00000546329, ENST00000674164, ENST00000674397, ENST00000853989, ENST00000853990

RefSeq mRNA: 4 — MANE Select: NM_175739 NM_001042518, NM_001284275, NM_001284276, NM_175739

CCDS: CCDS41982, CCDS41983, CCDS61542, CCDS91925

Canonical transcript exons

ENST00000674397 — 5 exons

Exon	Start	End
ENSE00001226180	94464707	94464854
ENSE00001661559	94476136	94476197
ENSE00002241844	94462721	94463296
ENSE00003459418	94467109	94467382
ENSE00003489074	94469213	94469857

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 82.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.6378 / max 298.3854, expressed in 135 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144748	3.3166	120
144749	0.2888	89
144750	0.0324	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	82.76	silver quality
superficial temporal artery	UBERON:0001614	79.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.81	silver quality
lymph node	UBERON:0000029	76.43	gold quality
nasal cavity epithelium	UBERON:0005384	75.95	gold quality
vermiform appendix	UBERON:0001154	75.52	gold quality
caecum	UBERON:0001153	75.22	gold quality
gingival epithelium	UBERON:0001949	75.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.87	gold quality
cardia of stomach	UBERON:0001162	73.71	gold quality
superior surface of tongue	UBERON:0007371	73.18	silver quality
sperm	CL:0000019	72.89	gold quality
oocyte	CL:0000023	72.64	gold quality
ventral tegmental area	UBERON:0002691	72.30	gold quality
germinal epithelium of ovary	UBERON:0001304	72.13	gold quality
gingiva	UBERON:0001828	72.13	gold quality
vena cava	UBERON:0004087	71.98	gold quality
tongue	UBERON:0001723	71.83	silver quality
subthalamic nucleus	UBERON:0001906	71.81	gold quality
saphenous vein	UBERON:0007318	71.57	gold quality
dorsal plus ventral thalamus	UBERON:0001897	71.44	gold quality
trachea	UBERON:0003126	71.43	gold quality
inferior vagus X ganglion	UBERON:0005363	71.41	gold quality
cerebellar vermis	UBERON:0004720	71.30	gold quality
mammary duct	UBERON:0001765	71.28	gold quality
pylorus	UBERON:0001166	71.16	gold quality
body of tongue	UBERON:0011876	71.14	gold quality
pharyngeal mucosa	UBERON:0000355	71.11	gold quality
thymus	UBERON:0002370	71.00	gold quality
pericardium	UBERON:0002407	70.97	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting SERPINA9, 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-4760-3P	99.93	70.50	2385
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-455-5P	98.74	67.31	795
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-490-3P	97.79	65.54	606
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-6855-5P	97.51	66.03	830
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-3170	95.84	64.32	721

Literature-anchored findings (GeneRIF, showing 7)

• Results report the cloning of germinal center B-cell expressed transcripts 1 and 2 (GCET1 and 2), and show that both are expressed in follicular lymphoma and diffuse large B-cell lymphoma with germinal center B-cell differentiation. (PMID:12819018)
• The cloning, expression and molecular characterization of recombinant serpina9 (centerin) are reported. (PMID:17447896)
• Gcet-1 protein expression is restricted to a subset of germinal center B cells, establishing the existence of a distinct heterogeneity among normal and neoplastic germinal center B cells (PMID:17898315)
• Immunohistochemical expression of centerin further defines the germinal center cell origin of a subgroup of lymphomas. (PMID:18550480)
• serpinA9 was associated with stroke in both whites and blacks (PMID:18799872)
• Diagnostic Utility of the Germinal Center-associated Markers GCET1, HGAL, and LMO2 in Hematolymphoid Neoplasms. (PMID:25203428)
• Value of GCET1, HGAL (GCET2), and LMO2 in the Determination of Germinal Center Phenotype in Diffuse Large B-cell Lymphoma. (PMID:37519110)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpina9	ENSMUSG00000058260
rattus_norvegicus	Serpina9	ENSRNOG00000042391

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), 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 A9 — Q86WD7 (reviewed: Q86WD7)

Alternative names: Centerin, Germinal center B-cell-expressed transcript 1 protein

All UniProt accessions (3): Q86WD7, A0A6Q8JH89, A0A6Q8LYX2

UniProt curated annotations — full annotation on UniProt →

Function. Protease inhibitor that inhibits trypsin and trypsin-like serine proteases (in vitro). Inhibits plasmin and thrombin with lower efficiency (in vitro).

Subcellular location. Secreted Cytoplasm Cytoplasm Cytoplasm Cytoplasm Cytoplasm Membrane.

Tissue specificity. Highly expressed in normal germinal center (GC) B-cells and GC B-cell-derived malignancies.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the serpin family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q86WD7-1	1, A	yes
Q86WD7-2	2, B
Q86WD7-3	3, SERPINA11a
Q86WD7-4	4, SERPINA11b
Q86WD7-5	5
Q86WD7-6	6
Q86WD7-7	7

RefSeq proteins (4): NP_001035983, NP_001271204, NP_001271205, NP_783866* (*=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 (25 total): splice variant 8, sequence conflict 8, sequence variant 5, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WD7-F1	86.78	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 101, 390

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GARY_CD5_TARGETS_DN, chr14q32, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_SERINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MARTENS_TRETINOIN_RESPONSE_UP, CHICAS_RB1_TARGETS_SENESCENT, SERVITJA_ISLET_HNF1A_TARGETS_UP, SERVITJA_LIVER_HNF1A_TARGETS_DN, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, MIR6878_5P, MIR544A, MIR3192_5P, GSE12366_GC_VS_NAIVE_BCELL_UP

GO Biological Process (0):

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

GO Cellular Component (4): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), membrane (GO:0016020), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINA9	MME	P08473	713
SERPINA9	A0A3B3IT14	A0A3B3IT14	620
SERPINA9	FOXP1	Q9H334	620
SERPINA9	BCL6	P41182	583
SERPINA9	LMO2	P25791	507
SERPINA9	GCSAM	Q8N6F7	506
SERPINA9	FAM20A	Q96MK3	456
SERPINA9	MXRA8	Q9BRK3	423
SERPINA9	WFS1	O76024	421
SERPINA9	PRSS23	O95084	419
SERPINA9	IRF4	Q15306	413
SERPINA9	DPP7	Q9UHL4	381
SERPINA9	POU2AF3	A8K830	367
SERPINA9	PPP4R4	Q6NUP7	359
SERPINA9	HSPA13	P48723	346

IntAct

8 interactions, top by confidence:

A	B	Type	Score
SERPINA9	FBXO2	psi-mi:“MI:0915”(physical association)	0.400
GABPA	A2ML1	psi-mi:“MI:0914”(association)	0.350
NRSN1	IGLC7	psi-mi:“MI:0914”(association)	0.350
RNF115	IGLC7	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SARAF	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): SERPINA9 (Affinity Capture-MS), SERPINA9 (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), SERPINA9 (Affinity Capture-MS), SERPINA9 (Affinity Capture-MS), SERPINA9 (Affinity Capture-MS), SERPINA9 (Affinity Capture-MS), SERPINA9 (Affinity Capture-MS), SERPINA9 (Affinity Capture-MS)

ESM2 similar proteins: A2I7M9, A2I7N0, A2I7N1, A2I7N2, A2I7N3, A6QPQ2, B2D1U1, E1BF81, O54762, P01011, P05154, P05544, P05545, P07759, P08185, P09006, P22323, P22324, P22325, P22599, P26595, P29621, P29622, P31211, P50451, P70458, Q00896, Q00897, Q00898, Q03044, Q03734, Q3ZEJ6, Q5I2A0, Q5R536, Q5R9E3, Q5RCR2, Q60396, Q63556, Q63969, Q64118

Diamond homologs: A0A090BX51, A0A0K8RCY5, A0A0K8RJ89, A0A0K8RJV9, A2I7M9, A2I7N0, A2I7N1, A2I7N2, A2I7N3, A5PJK0, A6QPQ2, A9RA96, B0CMB0, B1MTC3, B2KI30, B3RFC3, B4USX2, O02739, O08800, O35684, O54757, O54758, O54759, O54760, O73790, O75830, P01008, P01011, P05120, P05154, P05544, P05545, P05619, P07759, P08185, P09006, P23775, P29508, P29524, P29621

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

894 predictions. Top by Δscore:

Variant	Effect	Δscore
14:94463293:TTGC:T	acceptor_gain	1.0000
14:94463297:C:CA	acceptor_loss	1.0000
14:94463297:C:CC	acceptor_gain	1.0000
14:94463298:T:A	acceptor_loss	1.0000
14:94464703:TCA:T	donor_loss	1.0000
14:94464704:CACTT:C	donor_loss	1.0000
14:94464705:A:AC	donor_gain	1.0000
14:94464705:AC:A	donor_loss	1.0000
14:94464706:C:CA	donor_gain	1.0000
14:94464850:TCCAC:T	acceptor_gain	1.0000
14:94464851:CCACC:C	acceptor_gain	1.0000
14:94464852:CAC:C	acceptor_gain	1.0000
14:94464853:ACC:A	acceptor_loss	1.0000
14:94464854:CCTG:C	acceptor_loss	1.0000
14:94464855:C:CC	acceptor_gain	1.0000
14:94467378:CTTGG:C	acceptor_gain	1.0000
14:94467383:C:CC	acceptor_gain	1.0000
14:94463294:TGC:T	acceptor_gain	0.9900
14:94463295:GC:G	acceptor_gain	0.9900
14:94463296:CC:C	acceptor_gain	0.9900
14:94464706:CT:C	donor_gain	0.9900
14:94464851:CCAC:C	acceptor_gain	0.9900
14:94464852:CACC:C	acceptor_gain	0.9900
14:94464862:G:C	acceptor_gain	0.9900
14:94464862:G:GC	acceptor_gain	0.9900
14:94467104:CCCA:C	donor_loss	0.9900
14:94467105:CCA:C	donor_loss	0.9900
14:94467106:CA:C	donor_loss	0.9900
14:94467108:CCT:C	donor_loss	0.9900
14:94467387:C:CT	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000301804 (14:94468798 C>T), RS1000455415 (14:94463531 A>C), RS1000509602 (14:94467762 C>A,T), RS1000584659 (14:94473546 A>G), RS1000638412 (14:94473311 G>A), RS1000777055 (14:94462430 T>C), RS1000887715 (14:94463880 T>C), RS1000973931 (14:94472635 G>C), RS1001090458 (14:94477521 G>A,T), RS1001203776 (14:94464452 C>A,T), RS1001206667 (14:94475905 A>C,G,T), RS1001269593 (14:94477163 C>A,T), RS1001721541 (14:94469721 A>T), RS1002089333 (14:94473043 A>G), RS1002314493 (14:94468565 T>C)

Disease associations

OMIM: gene MIM:615677 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_666	Blood protein levels	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Latex	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression, affects response to substance	1
Tetrachlorodibenzodioxin	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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