SIGLEC9

Summary

SIGLEC9 (sialic acid binding Ig like lectin 9, HGNC:10878) is a protein-coding gene on chromosome 19q13.41, encoding Sialic acid-binding Ig-like lectin 9 (Q9Y336). Putative adhesion molecule that mediates sialic-acid dependent binding to cells.

Predicted to enable monosaccharide binding activity and sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within negative regulation of inflammatory response and negative regulation of phagocytosis, engulfment. Predicted to be located in external side of plasma membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 27180 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 70 total
• Druggable target: yes
• MANE Select transcript: NM_014441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10878
Approved symbol	SIGLEC9
Name	sialic acid binding Ig like lectin 9
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	CD329
Ensembl gene	ENSG00000129450
Ensembl biotype	protein_coding
OMIM	605640
Entrez	27180

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000250360, ENST00000440804, ENST00000599948, ENST00000850849, ENST00000850850, ENST00000860863, ENST00000860864, ENST00000966614

RefSeq mRNA: 2 — MANE Select: NM_014441 NM_001198558, NM_014441

CCDS: CCDS12825, CCDS56100

Canonical transcript exons

ENST00000250360 — 7 exons

Exon	Start	End
ENSE00000722578	51127030	51127296
ENSE00001125657	51127949	51128039
ENSE00001125679	51129891	51130310
ENSE00002436763	51128414	51128510
ENSE00002528825	51126081	51126128
ENSE00002531406	51125597	51125875
ENSE00003915131	51124906	51125395

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 95.84.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0076 / max 91.9144, expressed in 339 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177191	1.8920	336
177192	0.1156	74

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	95.84	gold quality
mononuclear cell	CL:0000842	95.55	gold quality
leukocyte	CL:0000738	95.43	gold quality
granulocyte	CL:0000094	94.03	gold quality
blood	UBERON:0000178	88.78	gold quality
spleen	UBERON:0002106	87.09	gold quality
upper lobe of left lung	UBERON:0008952	79.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.91	silver quality
right adrenal gland cortex	UBERON:0035827	78.91	gold quality
vermiform appendix	UBERON:0001154	78.32	gold quality
right adrenal gland	UBERON:0001233	78.01	gold quality
right lung	UBERON:0002167	77.76	gold quality
left adrenal gland	UBERON:0001234	77.59	gold quality
left adrenal gland cortex	UBERON:0035825	77.46	gold quality
upper lobe of lung	UBERON:0008948	76.53	gold quality
adrenal cortex	UBERON:0001235	75.71	gold quality
gall bladder	UBERON:0002110	74.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.31	gold quality
adrenal gland	UBERON:0002369	73.74	gold quality
omental fat pad	UBERON:0010414	73.51	gold quality
peritoneum	UBERON:0002358	73.42	gold quality
left coronary artery	UBERON:0001626	72.99	gold quality
descending thoracic aorta	UBERON:0002345	72.70	gold quality
adipose tissue of abdominal region	UBERON:0007808	72.51	gold quality
right coronary artery	UBERON:0001625	72.40	gold quality
caecum	UBERON:0001153	72.08	gold quality
left uterine tube	UBERON:0001303	71.98	gold quality
right ovary	UBERON:0002118	71.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	71.59	gold quality
smooth muscle tissue	UBERON:0001135	71.58	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.00
E-MTAB-9801	yes	6.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting SIGLEC9, 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-3120-5P	100.00	65.56	965
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-8056	97.15	64.49	769
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-549A-5P	96.35	68.08	587

Literature-anchored findings (GeneRIF, showing 40)

• Binding studies on recombinant human Siglec-9 show recognition of both Neu5Ac and Neu5Gc; in striking contrast, chimpanzee and gorilla Siglec-9 strongly prefer binding Neu5Gc. (PMID:14693915)
• Siglec-7 and Siglec-9 are capable of negative regulation of TCR signaling and ligand binding is required for optimal activity (PMID:15292262)
• Siglec-9 can inhibit Fc epsilon receptor I-mediated serotonin release from rat basophilic leukemia cells and recruit the tyrosine phosphatases SHP-1 and SHP-2. (PMID:15557178)
• data suggest that apoptotic (ROS- and caspase-dependent) and nonapoptotic (ROS-dependent) death pathways are initiated in neutrophils via Siglec-9 (PMID:15827126)
• Siglecs-9 did not interact with sulfate derivatives of LacNAc and sulfated oligosaccharides containing sialic acid. (PMID:16732727)
• The Siglec-9 provides not only a useful marker for certain subsets of AML, but also a potential therapeutic target. (PMID:16828866)
• These results demonstrate that Siglec-9 enhances the production of the anti-inflammatory cytokine IL-10 in macrophages. (PMID:18325328)
• A review of the cytotoxic effects of natural anti-Siglec9 autoantibodies on both neutrophils and eosinophils. (PMID:18558361)
• Increased bacterial survival are also facilitated by group b Streptococcus sialylated capsular polysaccharide interactions with Siglec-9. (PMID:19196661)
• Septic shock patients exhibit different ex vivo death responses of blood neutrophils after Siglec-9 ligation early in shock. (PMID:19295491)
• Data suggest that age-specific interactions between Siglec-9 and SHP-1 may influence the altered inflammatory responsiveness and longevity of neonatal polymorphonuclear neutrophils. (PMID:19542910)
• MUC16-Siglec-9 binding likely mediates inhibition of anti-tumor immune responses. (PMID:20497550)
• Siglec-9 A391C was the only polymorphism related to TCR-mediated signaling in human Siglec-9, resulting in less inhibition compared to the wild type. (PMID:20733319)
• These results suggest that Siglec-9 expressed on DCs is involved in immunoregulation through ligation with mucins in an epithelial cancer patient. (PMID:20971061)
• The Siglec-9 peptide binding to the enzymatic groove of VAP-1 can be used for imaging conditions, such as inflammation and cancer. (PMID:21821708)
• Siglec-9 expressed on immune cells may play a role as a potential counterreceptor for MUC1 and that this signaling may be another MUC1-mediated pathway and function in parallel with a growth factor-dependent pathway. (PMID:24045940)
• Protein degradation of focal adhesion kinase and related molecules was induced by Siglec-9 binding to its counterreceptors via sialylglycoconjugates, leading to the modulation of adhesion kinetics of cancer cells. (PMID:24145038)
• Expression of Siglec-7 and -9 ligands was associated with susceptibility of NK cell-sensitive tumor cells and, unexpectedly, of presumably NK cell-resistant tumor cells to NK cell-mediated cytotoxicity. (PMID:24569453)
• Dasatinib enhances migration of monocyte-derived dendritic cells by reducing phosphorylation of inhibitory immune receptors Siglec-9 and Siglec-3. (PMID:24882272)
• a polymorphism that reduced Siglec-9 binding to carcinomas was associated with improved early survival in non-small-cell lung cancer patients (PMID:25225409)
• Inflammation results in up-regulation of immuneinhibitory Siglec-8 and Siglec-9 sialoglycan ligands on human airways. (PMID:25747723)
• Ligands for Siglec-8 and Siglec-9 may regulate the function of eosinophils, mast cells, neutrophils, and other cells in sinus mucosa. (PMID:26694037)
• Constitutively expressed Siglec-9 inhibits LPS-induced CCR7, but enhances IL-4-induced CD200R expression in human macrophages. (PMID:26923638)
• This work defines a critical role for aberrantly glycosylated MUC1 and identifies an activating pathway that follows engagement of Siglec-9. (PMID:27595232)
• The SIGLEC9 rs2075803 G/rs2258983 A haplotype, which corresponds to a Siglec-9 variant that is less effective at suppressing inflammatory response, may be a risk factor for the development of emphysema. (PMID:27878892)
• The mechanism of the Siglec-9 and AOC3 interaction is mediated both by protein-sugar interactions via the V domain and by the protein-protein interactions via the C22 Siglec9 domain. (PMID:27893774)
• Data suggest that sialic acid-binding Ig-like lectin-9 (Siglec-9)may serve as a potential diagnostic and therapeutic target for rheumatoid arthritis (RA). (PMID:28273363)
• Glycophorin A, the most abundant sialoglycoprotein on erythrocytes, engaged neutrophil Siglec-9, a sialic acid-recognizing receptor known to dampen innate immune cell activation. These studies demonstrate a previously unsuspected role for erythrocytes in suppressing neutrophils ex vivo and in vitro and help explain why neutrophils become easily activated after separation from whole blood. (PMID:28416510)
• Siglec-9 expression is upregulated in chronic obstructive pulmonary disease. (PMID:28860481)
• These findings identify Siglec-9 as a negative regulator for NK cells contributing to HBV persistence and the intervention of Siglec-9 signaling might be of potentially translational significance. (PMID:29899741)
• Targeting of the sialoglycan-SAMP/Siglec pathway in vitro and in vivo resulted in increased anticancer immunity. T cell expression of Siglec-9 in NSCLC patients correlated with reduced survival, and Siglec-9 polymorphisms showed association with the risk of developing lung and colorectal cancer. (PMID:30130255)
• Expression of cognate Siglec-9 ligands was observed on the majority of tumor cells in primary and metastatic melanoma specimens. Targeting the tumor-restricted, glycosylation-dependent Siglec-9 axis may unleash this intratumoral T-cell subset, while confining T-cell activation to the tumor microenvironment. (PMID:30988027)
• SS erythrocytes are deficient in binding to neutrophil Siglec-9 which may contribute to the increased oxidative stress in SCD. (PMID:31901888)
• The Roles of Siglec7 and Siglec9 on Natural Killer Cells in Virus Infection and Tumour Progression. (PMID:32322597)
• Targeting glycosylated antigens on cancer cells using siglec-7/9-based CAR T-cells. (PMID:32391973)
• Modulation of immune cell reactivity with cis-binding Siglec agonists. (PMID:33431669)
• Identification and validation of a siglec-based and aging-related 9-gene signature for predicting prognosis in acute myeloid leukemia patients. (PMID:35854240)
• LINC01004-SPI1 axis-activated SIGLEC9 in tumor-associated macrophages induces radioresistance and the formation of immunosuppressive tumor microenvironment in esophageal squamous cell carcinoma. (PMID:36688997)
• Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2. (PMID:36728420)
• Siglec-9 acts as an immune-checkpoint molecule on macrophages in glioblastoma, restricting T-cell priming and immunotherapy response. (PMID:37460871)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Siglece	ENSMUSG00000030474
rattus_norvegicus	Siglec8	ENSRNOG00000022640

Paralogs (16): CD22 (ENSG00000012124), SIGLEC1 (ENSG00000088827), SIGLEC8 (ENSG00000105366), CD33 (ENSG00000105383), SIGLEC6 (ENSG00000105492), MAG (ENSG00000105695), SIGLEC10 (ENSG00000142512), TMEM25 (ENSG00000149582), SIGLEC11 (ENSG00000161640), SIGLEC16 (ENSG00000161643), SIGLEC7 (ENSG00000168995), SIGLECL1 (ENSG00000179213), SIGLEC15 (ENSG00000197046), SIGLEC14 (ENSG00000254415), SIGLEC12 (ENSG00000254521), SIGLEC5 (ENSG00000268500)

Protein

Protein identifiers

Sialic acid-binding Ig-like lectin 9 — Q9Y336 (reviewed: Q9Y336)

Alternative names: CDw329, Protein FOAP-9

All UniProt accessions (2): Q9Y336, M0R2D4

UniProt curated annotations — full annotation on UniProt →

Function. Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface.

Subcellular location. Membrane.

Tissue specificity. Expressed by peripheral blood leukocytes (neutrophils and monocytes but not eosinophils). Found in liver, fetal liver, bone marrow, placenta, spleen and in lower levels in skeletal muscle, fetal brain, stomach, lung, thymus, prostate, brain, mammary, adrenal gland, colon, trachea, cerebellum, testis, small intestine and spinal cordon.

Domain organisation. Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Similarity. Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y336-1	1	yes
Q9Y336-2	2

RefSeq proteins (2): NP_001185487, NP_055256* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051036	SIGLEC	Family

Pfam: PF00047, PF07686

UniProt features (35 total): glycosylation site 8, sequence variant 7, disulfide bond 4, domain 3, short sequence motif 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, binding site 1, splice variant 1, transmembrane region 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y336-F1	74.10	0.37

Functional residue map

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

Ligand- & substrate-binding residues (1): 120

Disulfide bonds (4): 36–170, 41–102, 164–213, 272–320

Glycosylation sites (8): 101, 138, 161, 225, 231, 238, 256, 334

Mutagenesis-validated functional residues (1):

Position	Phenotype
120	loss of sialic acid binding.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-6798695	Neutrophil degranulation
R-HSA-1280218	Adaptive Immune System
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 64 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, MODULE_544, GOCC_SECRETORY_VESICLE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOMF_ORGANIC_ACID_BINDING, VERHAAK_GLIOBLASTOMA_MESENCHYMAL, MODULE_481, GOMF_SIALIC_ACID_BINDING, REACTOME_NEUTROPHIL_DEGRANULATION, IL2_UP.V1_UP, STK33_NOMO_UP, NFKBIA_TARGET_GENES, MIR4760_3P

GO Biological Process (2): cell adhesion (GO:0007155), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (3): carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), secretory granule membrane (GO:0030667), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Immune System	2
Adaptive Immune System	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular process	1
signal transduction	1
carboxylic acid binding	1
carbohydrate derivative binding	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIGLEC9	AOC3	Q16853	977
SIGLEC9	MUC1	P13931	967
SIGLEC9	MUC16	Q8WXI7	885
SIGLEC9	KLK14	Q9P0G3	838
SIGLEC9	KLK13	Q9UKR3	762
SIGLEC9	PTPN11	Q06124	637
SIGLEC9	FCGR3A	P08637	586
SIGLEC9	FCGR3B	O75015	584
SIGLEC9	SLAMF1	Q13291	561
SIGLEC9	EEF1A2	P54266	549
SIGLEC9	ST6GAL1	P15907	548
SIGLEC9	SIGLEC15	Q6ZMC9	539
SIGLEC9	CD47	Q08722	525
SIGLEC9	KLK4	Q9Y5K2	521
SIGLEC9	GYPA	P02724	470
SIGLEC9	SH2D1A	O60880	470

IntAct

37 interactions, top by confidence:

A	B	Type	Score
NCS1	SIGLEC9	psi-mi:“MI:0915”(physical association)	0.560
SFTPC	SIGLEC9	psi-mi:“MI:0915”(physical association)	0.560
BRICD5	SIGLEC9	psi-mi:“MI:0915”(physical association)	0.560
SIGLEC9	TLR4	psi-mi:“MI:0915”(physical association)	0.540
SIGLEC9	TLR4	psi-mi:“MI:0407”(direct interaction)	0.540
SIGLEC9	TLR5	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR1	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR2	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR3	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR7	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR8	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR9	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	TLR10	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	NCAM1	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	CD33	psi-mi:“MI:0915”(physical association)	0.400
LILRB2	SIGLEC9	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	MAG	psi-mi:“MI:0915”(physical association)	0.400
PDGFRB	SIGLEC9	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	SIGLEC15	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400
ADGRA2	SIGLEC9	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	BOC	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	IL1RL1	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	IFNGR1	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	SIGLEC10	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (13): LGALS3BP (Affinity Capture-Western), LGALS3BP (Affinity Capture-MS), LGALS3BP (Reconstituted Complex), NCAM1 (Affinity Capture-MS), NCAM1 (Affinity Capture-MS), PTPN6 (Affinity Capture-Western), PTPN11 (Affinity Capture-Western), SIGLEC9 (Two-hybrid), SFTPC (Two-hybrid), BRICD5 (Two-hybrid), SIGLEC9 (Reconstituted Complex), S (Reconstituted Complex), NCAM1 (Affinity Capture-MS)

ESM2 similar proteins: A2A7V7, A2TGX5, A5D7B2, A8K4G0, B6A8R8, C0HJX2, C0HJX3, O15389, O43699, O95944, P12318, P20138, P24071, P27645, P43626, P43627, P43628, P43629, P43630, P43631, P43632, P50283, Q1ERP8, Q3LRV9, Q3U497, Q566E6, Q60513, Q6DN72, Q6SJQ0, Q6SJQ5, Q6SJQ7, Q6UXG3, Q6UXN2, Q6UXZ3, Q7TSN2, Q8K249, Q8N109, Q8NHK3, Q8R4Y0, Q8SPV8

Diamond homologs: A6NMB1, D3YXG0, O15389, O43699, O60469, P20138, P35329, Q08ET2, Q63994, Q64JA4, Q80ZE3, Q8N441, Q8VHZ8, Q91Y57, Q920G3, Q95LH0, Q96LC7, Q96PQ1, Q96RL6, Q96RW7, Q9ERC8, Q9NYZ4, Q9Y286, Q9Y336, Q460M5, Q6ZMC9, Q80TG9, Q8N7X8, Q9BE71, Q9ULH4, A1KZ92, A2AJ76, A2ASS6, P98160, Q28173, Q62151, Q63495, Q8BQC3, Q8NDA2, Q9QZS7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	5	18.9×	2e-04
Adaptive Immune System	5	6.5×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
toll-like receptor signaling pathway	9	208.3×	2e-17
positive regulation of interferon-alpha production	5	124.6×	2e-08
positive regulation of interferon-beta production	6	90.4×	3e-09
positive regulation of chemokine production	6	86.4×	3e-09
positive regulation of interleukin-8 production	8	75.2×	1e-11
positive regulation of interleukin-6 production	8	51.3×	2e-10
cellular response to mechanical stimulus	6	49.9×	6e-08
positive regulation of type II interferon production	5	43.2×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

926 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51125876:G:GG	donor_gain	1.0000
19:51127295:GA:G	donor_gain	1.0000
19:51127297:G:GG	donor_gain	1.0000
19:51128035:GTTGT:G	donor_gain	1.0000
19:51128038:GT:G	donor_gain	1.0000
19:51128040:G:GG	donor_gain	1.0000
19:51128412:A:AG	acceptor_gain	1.0000
19:51128413:G:GG	acceptor_gain	1.0000
19:51128413:GAGT:G	acceptor_gain	1.0000
19:51125345:G:GT	donor_gain	0.9900
19:51125393:CAGG:C	donor_loss	0.9900
19:51125395:GGTAA:G	donor_loss	0.9900
19:51125396:GTAAG:G	donor_loss	0.9900
19:51125397:T:G	donor_loss	0.9900
19:51125871:GTCCT:G	donor_gain	0.9900
19:51127028:A:AG	acceptor_gain	0.9900
19:51127029:G:GA	acceptor_gain	0.9900
19:51127292:GCAGA:G	donor_gain	0.9900
19:51127293:CAGAG:C	donor_loss	0.9900
19:51127294:AGAGT:A	donor_loss	0.9900
19:51127295:GAGTG:G	donor_loss	0.9900
19:51127296:AG:A	donor_loss	0.9900
19:51127297:GTGA:G	donor_loss	0.9900
19:51127299:GAGT:G	donor_loss	0.9900
19:51128408:A:AG	acceptor_gain	0.9900
19:51128412:AGAGT:A	acceptor_gain	0.9900
19:51128413:GA:G	acceptor_gain	0.9900
19:51128413:GAGTG:G	acceptor_gain	0.9900
19:51128507:TCAGG:T	donor_loss	0.9900
19:51128508:CAGG:C	donor_loss	0.9900

AlphaMissense

2965 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51125245:T:C	F91L	0.984
19:51125247:C:A	F91L	0.984
19:51125247:C:G	F91L	0.984
19:51125158:T:C	F62L	0.983
19:51125160:C:A	F62L	0.983
19:51125160:C:G	F62L	0.983
19:51125157:G:C	W61C	0.965
19:51125157:G:T	W61C	0.965
19:51125246:T:C	F91S	0.961
19:51125278:T:A	C102S	0.960
19:51125279:G:C	C102S	0.960
19:51125333:G:C	R120P	0.959
19:51125159:T:C	F62S	0.956
19:51125159:T:G	F62C	0.955
19:51125812:T:A	C213S	0.954
19:51125813:G:C	C213S	0.954
19:51125246:T:G	F91C	0.953
19:51125812:T:C	C213R	0.953
19:51125197:G:C	A75P	0.948
19:51125715:G:C	W180C	0.948
19:51125715:G:T	W180C	0.948
19:51125155:T:A	W61R	0.947
19:51125155:T:C	W61R	0.947
19:51125330:T:C	F119S	0.947
19:51125329:T:C	F119L	0.946
19:51125331:T:A	F119L	0.946
19:51125331:T:G	F119L	0.946
19:51125713:T:A	W180R	0.945
19:51125713:T:C	W180R	0.945
19:51125323:T:G	Y117D	0.942

dbSNP variants (sampled 300 via entrez): RS1000169875 (19:51118165 C>T), RS1000188206 (19:51122788 C>G,T), RS1000774966 (19:51119358 C>T), RS1000992911 (19:51124511 G>A,C,T), RS1001211537 (19:51124007 C>T), RS1001271051 (19:51118338 G>A), RS1001323223 (19:51118199 A>C), RS1001337297 (19:51128947 C>T), RS1001457836 (19:51133874 C>T), RS1001535775 (19:51134374 G>T), RS1001833605 (19:51133694 C>G,T), RS1002058782 (19:51128808 A>G), RS1002184153 (19:51119363 A>C), RS1002220330 (19:51119789 C>A), RS1002308393 (19:51129902 T>G)

Disease associations

OMIM: gene MIM:605640 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004608_140	Granulocyte percentage of myeloid white cells	2.000000e-10
GCST004609_154	Monocyte percentage of white cells	5.000000e-12
GCST008129_32	Body mass index	1.000000e-08
GCST008478_54	Neurological blood protein biomarker levels	3.000000e-21
GCST009268_6	Dental caries (decayed, missing and filled tooth surfaces)	3.000000e-06
GCST90002394_563	Monocyte percentage of white cells	2.000000e-21

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105860 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 5 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.41	IC50	3873	nM	CHEMBL3469788
5.15	IC50	7127	nM	CHEMBL3469788
5.04	IC50	9225	nM	CHEMBL3469788
5.03	IC50	9356	nM	CHEMBL3469788

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium bichromate	decreases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
abrine	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Fluorouracil	affects reaction, decreases expression	1
Lipopolysaccharides	increases expression, affects cotreatment, decreases expression, affects response to substance	1
Nickel	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3993870	Binding	Binding affinity to human IgG1-fused Siglec-9-Fc assessed as inhibition of Siglec-9-Fc binding to K562 cells preincubated for 10 mins followed by K562 cell addition measured after 20 mins by FACS analysis	Design, Synthesis, and Biological Evaluation of Small, High-Affinity Siglec-7 Ligands: Toward Novel Inhibitors of Cancer Immune Evasion. — J Med Chem

Cellosaurus cell lines

4 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7BV	Abeomics CHO-K1 SIGLEC9	Spontaneously immortalized cell line	Female
CVCL_E1DA	Ubigene THP-1 SIGLEC9 KO	Cancer cell line	Male
CVCL_E6RS	Genomeditech CHO-K1 H_SIGLEC9	Spontaneously immortalized cell line	Female
CVCL_E6UW	Genomeditech HEK-293 H_SIGLEC9	Transformed cell line	Female

Clinical trials (associated diseases)

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