SIGLEC7

Summary

SIGLEC7 (sialic acid binding Ig like lectin 7, HGNC:10876) is a protein-coding gene on chromosome 19q13.41, encoding Sialic acid-binding Ig-like lectin 7 (Q9Y286). Putative adhesion molecule that mediates sialic-acid dependent binding to cells.

Predicted to enable sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 27036 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 71 total
• Druggable target: yes
• MANE Select transcript: NM_014385

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10876
Approved symbol	SIGLEC7
Name	sialic acid binding Ig like lectin 7
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	SIGLEC-7, p75/AIRM1, QA79, CD328
Ensembl gene	ENSG00000168995
Ensembl biotype	protein_coding
OMIM	604410
Entrez	27036

Gene structure

Transcript identifiers

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

ENST00000305628, ENST00000317643, ENST00000536156, ENST00000599250, ENST00000600577, ENST00000601682, ENST00000880912, ENST00000880913, ENST00000880914, ENST00000880915, ENST00000965025, ENST00000965026

RefSeq mRNA: 3 — MANE Select: NM_014385 NM_001277201, NM_014385, NM_016543

CCDS: CCDS12826, CCDS42601, CCDS62771

Canonical transcript exons

ENST00000317643 — 7 exons

Exon	Start	End
ENSE00001187707	51145855	51146121
ENSE00001378905	51153063	51153526
ENSE00001509778	51142301	51142802
ENSE00002476791	51144406	51144684
ENSE00002493825	51144912	51144959
ENSE00002518175	51146754	51146850
ENSE00003534719	51147221	51147317

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 93.64.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1864 / max 45.1099, expressed in 249 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177196	0.8482	215
177195	0.2962	143
177197	0.0420	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.64	gold quality
monocyte	CL:0000576	92.94	gold quality
leukocyte	CL:0000738	92.70	gold quality
mononuclear cell	CL:0000842	92.68	gold quality
blood	UBERON:0000178	89.37	gold quality
spleen	UBERON:0002106	87.07	gold quality
cervix squamous epithelium	UBERON:0006922	85.03	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	82.67	gold quality
inferior olivary complex	UBERON:0002127	82.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.11	gold quality
sperm	CL:0000019	80.65	gold quality
male germ cell	CL:0000015	79.64	gold quality
vermiform appendix	UBERON:0001154	78.81	gold quality
caecum	UBERON:0001153	77.97	gold quality
amniotic fluid	UBERON:0000173	77.08	gold quality
lymph node	UBERON:0000029	76.03	gold quality
right adrenal gland cortex	UBERON:0035827	75.91	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.66	gold quality
trabecular bone tissue	UBERON:0002483	75.59	silver quality
choroid plexus epithelium	UBERON:0003911	75.24	gold quality
blood vessel layer	UBERON:0004797	75.17	gold quality
right adrenal gland	UBERON:0001233	74.64	gold quality
periodontal ligament	UBERON:0008266	74.33	gold quality
endothelial cell	CL:0000115	74.02	gold quality
right lobe of liver	UBERON:0001114	74.01	gold quality
adrenal cortex	UBERON:0001235	73.78	gold quality
vastus lateralis	UBERON:0001379	73.62	gold quality
left adrenal gland cortex	UBERON:0035825	73.44	gold quality
quadriceps femoris	UBERON:0001377	73.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting SIGLEC7, 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-1250-3P	99.96	70.04	4038
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-148B-5P	97.29	66.30	992
HSA-MIR-6874-3P	97.29	66.34	975
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-4793-5P	96.88	65.90	872

Literature-anchored findings (GeneRIF, showing 38)

• Regulation of myeloid cell proliferation and survival by p75/AIRM1 and CD33 surface receptors. (PMID:11774609)
• high resolution crystal structures of this protein; insights into ligand specificity of this family of proteins (PMID:12438315)
• Sialidase unmasking of siglec-7 on NK cells permits it to interact with GD3 on target cells and inhibit killing. This has inplications for tumor escape from NK cells. (PMID:12778482)
• x-ray crystallographic analysis of the saccharide-binding domain of p75/AIRM1 (PMID:14747738)
• Siglec-7 and Siglec-9 are capable of negative regulation of TCR signaling and ligand binding is required for optimal activity (PMID:15292262)
• Siglec-7 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)
• upon pervanadate (PV) treatment, Siglec-7 recruited the protein tyrosine phosphatases Src homology-2 (SH2) domain-containing protein-tyrosine phosphatase-1 and SHP-2 less efficiently than did other inhibitory receptors (PMID:15703304)
• structural analysis of siglec-7 in complex with sialosides (PMID:16623661)
• Siglecs-7 did not interact with sulfate derivatives of LacNAc and sulfated oligosaccharides containing sialic acid. (PMID:16732727)
• The expression levels of Siglec-7 were detectable in bone marrow plasma from AML patients and serum from normal donors. (PMID:16828866)
• The species-specific differences in the expression expression of Siglecs in SIV infection was studied. (PMID:18331725)
• The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia. (PMID:19710502)
• Based on upregulated SIGLEC7 expression in blood monocytes during relapse, findings suggest a role for SIGLEC7 in acute disease activity in multiple sclerosis. (PMID:22933622)
• Siglec-7 participates in generating a monocyte-mediated inflammatory outcome following pathogen recognition. (PMID:23029261)
• These results show that Siglec-7 binds HIV-1 via gp120 and contributes to enhance the susceptibility to infection of CD4 positive T cells and monocyte-derived macrophages. (PMID:24330394)
• 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)
• Siglec-7 plays a significant role in inhibiting IgE-mediated mast cell activation, but only moderately affects IgE-mediated activation in primary human basophils. (PMID:24810846)
• Siglec-7 defines a highly functional natural killer cell subset and inhibits cell-mediated activities. (PMID:27312286)
• Data reported that Siglec-7 was expressed on beta-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. Furthermore, Siglec-7 seems to play a critical role in the maintenance of an immune-suppressive anti-inflammatory microenvironment, which is lost in diabetes, and may contribute to the manifestation and progression of this metabolic syndrome. (PMID:28378743)
• CD56bright NK cells from obese subjects had a reduced expression of Siglec-7 (PMID:28786023)
• NK cells with Siglec-7neg phenotype possess a high and sustainable killing activity and have the capability to eliminate a NK-resistant leukemia cell and hypersialylated tumor cells (PMID:29617289)
• Siglec-7 is constitutively expressed on human eosinophils and downmodulates eosinophil activation. (PMID:30690753)
• DNA methylation-mediated Siglec-7 regulation in natural killer cells via two 5’ promoter CpG sites. (PMID:32027025)
• Reduced Siglec-7 expression on NK cells predicts NK cell dysfunction in primary hepatocellular carcinoma. (PMID:32319079)
• 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)
• Discovery of a new sialic acid binding region that regulates Siglec-7. (PMID:32457377)
• Decidual glycodelin-A polarizes human monocytes into a decidual macrophage-like phenotype through Siglec-7. (PMID:32513821)
• The conserved arginine residue in all siglecs is essential for Siglec-7 binding to sialic acid. (PMID:33248687)
• Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7. (PMID:33495350)
• Identification and functional characterization of a Siglec-7 counter-receptor on K562 cells. (PMID:33640457)
• Siglec-7 is an indicator of natural killer cell function in acute myeloid leukemia. (PMID:34273636)
• Siglec-7 mediates varicella-zoster virus infection by associating with glycoprotein B. (PMID:35367830)
• Regulation of Siglec-7-mediated varicella-zoster virus infection of primary monocytes by cis-ligands. (PMID:35526487)
• Siglec-7 represents a glyco-immune checkpoint for non-exhausted effector memory CD8+ T cells with high functional and metabolic capacities. (PMID:36211376)
• Histone deacetylation-regulated cell surface Siglec-7 expression promoted megakaryocytic maturation and enhanced platelet-like particle release. (PMID:36700509)
• The glycoimmune checkpoint receptor Siglec-7 interacts with T-cell ligands and regulates T-cell activation. (PMID:38141764)
• High expression of SIGLEC7 may promote M2-type macrophage polarization leading to adverse prognosis in glioma patients. (PMID:39211050)

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), SIGLEC9 (ENSG00000129450), SIGLEC10 (ENSG00000142512), TMEM25 (ENSG00000149582), SIGLEC11 (ENSG00000161640), SIGLEC16 (ENSG00000161643), SIGLECL1 (ENSG00000179213), SIGLEC15 (ENSG00000197046), SIGLEC14 (ENSG00000254415), SIGLEC12 (ENSG00000254521), SIGLEC5 (ENSG00000268500)

Protein

Protein identifiers

Sialic acid-binding Ig-like lectin 7 — Q9Y286 (reviewed: Q9Y286)

Alternative names: Adhesion inhibitory receptor molecule 1, CDw328, D-siglec, QA79 membrane protein, p75

All UniProt accessions (2): Q9Y286, M0QY65

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- and alpha-2,6-linked sialic acid. Also binds disialogangliosides (disialogalactosyl globoside, disialyl lactotetraosylceramide and disialyl GalNAc lactotetraoslylceramide). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Mediates inhibition of natural killer cells cytotoxicity. May play a role in hemopoiesis. Inhibits differentiation of CD34+ cell precursors towards myelomonocytic cell lineage and proliferation of leukemic myeloid cells (in vitro).

Subunit / interactions. Interacts with PTPN6/SHP-1 upon phosphorylation.

Subcellular location. Membrane.

Tissue specificity. Predominantly expressed by resting and activated natural killer cells and at lower levels by granulocytes and monocytes. High expression found in placenta, liver, lung, spleen, and peripheral blood leukocytes.

Post-translational modifications. Tyrosine phosphorylated.

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.

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 immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y286-1	1, AIRM-1b	yes
Q9Y286-2	2, AIRM-2
Q9Y286-3	3, AIRM-3
Q9Y286-4	4

RefSeq proteins (3): NP_001264130, NP_055200, NP_057627 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051036	SIGLEC	Family

Pfam: PF07686, PF13895

UniProt features (53 total): strand 12, glycosylation site 8, helix 6, splice variant 4, disulfide bond 3, domain 3, compositionally biased region 2, binding site 2, topological domain 2, turn 2, region of interest 2, signal peptide 1, chain 1, short sequence motif 1, modified residue 1, transmembrane region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1NKO	X-RAY DIFFRACTION	1.45
2G5R	X-RAY DIFFRACTION	1.6
1O7S	X-RAY DIFFRACTION	1.75
2HRL	X-RAY DIFFRACTION	1.85
1O7V	X-RAY DIFFRACTION	1.9
2DF3	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y286-F1	74.62	0.44

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 (2): 124; 131–135

Post-translational modifications (1): 429

Disulfide bonds (3): 46–106, 168–217, 276–320

Glycosylation sites (8): 105, 142, 165, 229, 235, 242, 260, 334

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 99 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, VALK_AML_CLUSTER_5, DR3_Q4, PARENT_MTOR_SIGNALING_DN, SHEN_SMARCA2_TARGETS_DN, GOMF_ORGANIC_ACID_BINDING, SENGUPTA_EBNA1_ANTICORRELATED, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP, VERHAAK_GLIOBLASTOMA_MESENCHYMAL, GOMF_SIALIC_ACID_BINDING, GSE10325_LUPUS_CD4_TCELL_VS_LUPUS_MYELOID_DN, GSE10325_LUPUS_BCELL_VS_LUPUS_MYELOID_DN, GSE12845_IGD_POS_VS_NEG_BLOOD_BCELL_UP, GSE12845_IGD_POS_BLOOD_VS_PRE_GC_TONSIL_BCELL_UP

GO Biological Process (1): cell adhesion (GO:0007155)

GO Molecular Function (4): carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular process	1
carboxylic acid binding	1
carbohydrate derivative binding	1
molecular transducer activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIGLEC7	KLK14	Q9P0G3	713
SIGLEC7	HLA-E	P13747	660
SIGLEC7	SIGLEC15	Q6ZMC9	637
SIGLEC7	ST8SIA6	P61647	614
SIGLEC7	PVR	P15151	604
SIGLEC7	SIGLEC1	Q9BZZ2	603
SIGLEC7	KLRC1	P26715	601
SIGLEC7	CD274	Q9NZQ7	588
SIGLEC7	LILRB1	Q8NHL6	581
SIGLEC7	NCR3	O14931	581
SIGLEC7	SOCS3	O14543	579
SIGLEC7	KLRC2	P26717	579
SIGLEC7	SH2D1A	O60880	566
SIGLEC7	ITIH4	Q14624	558
SIGLEC7	BTLA	Q7Z6A9	537

IntAct

23 interactions, top by confidence:

A	B	Type	Score
SMIM1	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.560
IFT74	LRRFIP1	psi-mi:“MI:0914”(association)	0.530
SIGLEC7	TLR4	psi-mi:“MI:0407”(direct interaction)	0.440
SIGLEC7	TLR3	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	TLR5	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	WDR89	psi-mi:“MI:0915”(physical association)	0.400
MXRA5	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400
BOC	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	CD33	psi-mi:“MI:0915”(physical association)	0.400
CD4	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400
LRRC4C	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400
NRG1	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	SIGLEC10	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	TIMD4	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	TNFRSF11B	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.400
BMP2K	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.370
SMIM1	SIGLEC7	psi-mi:“MI:0915”(physical association)	0.000
SIGLEC7	rph	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): LGALS3BP (Reconstituted Complex), SIGLEC7 (Affinity Capture-MS), WDR89 (Affinity Capture-MS), LGALS1 (Affinity Capture-MS), PTPN6 (Affinity Capture-Western), PTPN11 (Affinity Capture-Western), SMIM1 (Two-hybrid), SIGLEC7 (Affinity Capture-MS), WDR89 (Affinity Capture-MS), RPS27L (Cross-Linking-MS (XL-MS)), RPS27 (Cross-Linking-MS (XL-MS)), SIGLEC7 (Affinity Capture-Western)

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

2 interactions.

A	Effect	B	Mechanism
SOCS3	“down-regulates quantity by destabilization”	SIGLEC7	binding
“Elongin E3-Cul-5”	“down-regulates quantity by destabilization”	SIGLEC7	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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
Adaptive Immune System	5	10.7×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell adhesion	5	10.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

969 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51144685:G:GG	donor_gain	1.0000
19:51147220:GA:G	acceptor_gain	1.0000
19:51147220:GAGT:G	acceptor_gain	1.0000
19:51144680:GTCCT:G	donor_gain	0.9900
19:51147219:A:AG	acceptor_gain	0.9900
19:51147219:AGAGT:A	acceptor_gain	0.9900
19:51147220:G:GG	acceptor_gain	0.9900
19:51147220:GAGTG:G	acceptor_gain	0.9900
19:51142752:G:GT	donor_gain	0.9800
19:51142799:ACAGG:A	donor_loss	0.9800
19:51142800:CAGG:C	donor_loss	0.9800
19:51142802:GGTAA:G	donor_loss	0.9800
19:51142804:T:A	donor_loss	0.9800
19:51144910:A:AG	acceptor_gain	0.9800
19:51144911:G:GG	acceptor_gain	0.9800
19:51153061:AG:A	acceptor_gain	0.9800
19:51153062:GG:G	acceptor_gain	0.9800
19:51153062:GGGT:G	acceptor_gain	0.9800
19:51142753:A:T	donor_gain	0.9700
19:51144204:A:G	donor_gain	0.9700
19:51144904:T:A	acceptor_gain	0.9700
19:51144956:ACAG:A	donor_loss	0.9700
19:51144957:CAGGT:C	donor_loss	0.9700
19:51144958:AG:A	donor_loss	0.9700
19:51144959:GG:G	donor_loss	0.9700
19:51144960:GT:G	donor_loss	0.9700
19:51144961:T:A	donor_loss	0.9700
19:51147215:A:AG	acceptor_gain	0.9700
19:51153057:A:AG	acceptor_gain	0.9700
19:51153058:TTCA:T	acceptor_loss	0.9700

AlphaMissense

3016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51142652:T:C	F95L	0.974
19:51142654:C:A	F95L	0.974
19:51142654:C:G	F95L	0.974
19:51142564:G:C	W65C	0.946
19:51142564:G:T	W65C	0.946
19:51145932:A:C	S280R	0.940
19:51145934:C:A	S280R	0.940
19:51145934:C:G	S280R	0.940
19:51142511:T:C	F48L	0.936
19:51142513:C:A	F48L	0.936
19:51142513:C:G	F48L	0.936
19:51142565:T:C	F66L	0.934
19:51142567:C:A	F66L	0.934
19:51142567:C:G	F66L	0.934
19:51142562:T:A	W65R	0.923
19:51142562:T:C	W65R	0.923
19:51142740:G:C	R124P	0.923
19:51142653:T:C	F95S	0.922
19:51142685:T:A	C106S	0.919
19:51142686:G:C	C106S	0.919
19:51142653:T:G	F95C	0.912
19:51144524:G:C	W184C	0.912
19:51144524:G:T	W184C	0.912
19:51142505:T:A	C46S	0.911
19:51142506:G:C	C46S	0.911
19:51144621:T:C	C217R	0.910
19:51142698:T:C	I110T	0.908
19:51144621:T:A	C217S	0.908
19:51144622:G:C	C217S	0.908
19:51142604:G:C	A79P	0.902

dbSNP variants (sampled 300 via entrez): RS1000011167 (19:51150425 C>T), RS1000326181 (19:51144910 A>G), RS1000430846 (19:51145723 T>C), RS1000463572 (19:51145344 A>C), RS1000511834 (19:51148419 A>G), RS1000615116 (19:51151935 C>A), RS1000841379 (19:51143511 CG>C), RS1001049462 (19:51151706 G>A), RS1001082263 (19:51153677 T>A), RS1001528630 (19:51150225 G>A), RS1001905692 (19:51144761 C>A,T), RS1001949680 (19:51146092 T>C), RS1002068118 (19:51152309 A>G), RS1002075369 (19:51151033 G>C), RS1002372835 (19:51145789 A>T)

Disease associations

OMIM: gene MIM:604410 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002386_215	High light scatter reticulocyte percentage of red cells	3.000000e-09
GCST90002406_535	Reticulocyte fraction of red cells	8.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3603730 (SINGLE PROTEIN)

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

ChEMBL bioactivities

9 potent at pChembl≥5 of 10 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.57	Kd	26.8	nM	CHEMBL4547472
7.49	Kd	32.7	nM	CHEMBL4552690
7.41	Kd	38.7	nM	CHEMBL4447168
7.36	Kd	43.3	nM	CHEMBL4580652
7.31	Kd	48.7	nM	CHEMBL4469685
7.27	Kd	54.1	nM	CHEMBL4483422
7.22	Kd	60	nM	CHEMBL4552690
5.80	IC50	1600	nM	CHEMBL4096201
5.58	IC50	2600	nM	CHEMBL4060254

PubChem BioAssay actives

9 with measured affinity, of 91 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3S,4S,5R,6S)-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-6-[(2R,3S,4R,5R,6R)-6-(6-azidohexoxy)-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid	1570224: Binding affinity to recombinant human Fc-fused siglec-7 after 1 hr by fluorescence based glycan microarray analysis	kd	0.0268	uM
(2S,4S,5R,6R)-5-acetamido-6-[(1R,2R)-2-[(2S,4S,5R,6R)-5-acetamido-2-carboxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-1,3-dihydroxypropyl]-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-6-(6-azidohexoxy)-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxyoxane-2-carboxylic acid	1570224: Binding affinity to recombinant human Fc-fused siglec-7 after 1 hr by fluorescence based glycan microarray analysis	kd	0.0327	uM
(2R,4S,5R,6R)-5-acetamido-2-[[(2R,3S,4S,5R,6S)-6-[(2R,3S,4R,5R,6R)-5-acetamido-6-(6-azidohexoxy)-4-hydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-4-[(2S,4S,5R,6R)-5-acetamido-2-carboxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-3,5-dihydroxyoxan-2-yl]methoxy]-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxane-2-carboxylic acid	1570224: Binding affinity to recombinant human Fc-fused siglec-7 after 1 hr by fluorescence based glycan microarray analysis	kd	0.0387	uM
(2S,4S,5R,6R)-5-acetamido-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-6-(6-azidohexoxy)-4-hydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-6-[(1R,2R)-2-[(2S,4S,5R,6R)-5-acetamido-2-carboxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-1,3-dihydroxypropyl]-4-hydroxyoxane-2-carboxylic acid	1570224: Binding affinity to recombinant human Fc-fused siglec-7 after 1 hr by fluorescence based glycan microarray analysis	kd	0.0433	uM
(2S,4S,5R,6R)-5-acetamido-6-[(1R,2R)-2-[(2S,4S,5R,6R)-5-acetamido-6-[(1R,2R)-2-[(2S,4S,5R,6R)-5-acetamido-2-carboxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-1,3-dihydroxypropyl]-2-carboxy-4-hydroxyoxan-2-yl]oxy-1,3-dihydroxypropyl]-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-6-(6-azidohexoxy)-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxyoxane-2-carboxylic acid	1570224: Binding affinity to recombinant human Fc-fused siglec-7 after 1 hr by fluorescence based glycan microarray analysis	kd	0.0487	uM
(2S,4S,5R,6R)-5-acetamido-6-[(1R,2R)-2-[(2S,4S,5R,6R)-5-acetamido-6-[(1R,2R)-2-[(2S,4S,5R,6R)-5-acetamido-2-carboxy-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxy-1,3-dihydroxypropyl]-2-carboxy-4-hydroxyoxan-2-yl]oxy-1,3-dihydroxypropyl]-2-[(2S,3R,4S,5S,6R)-2-[(2R,3S,4R,5R,6R)-5-acetamido-6-(6-azidohexoxy)-4-hydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-4-hydroxyoxane-2-carboxylic acid	1570224: Binding affinity to recombinant human Fc-fused siglec-7 after 1 hr by fluorescence based glycan microarray analysis	kd	0.0541	uM
sodium (2R,4S,5R,6R)-5-acetamido-6-[(1R,2R)-3-(ethylsulfonylamino)-1,2-dihydroxypropyl]-4-hydroxy-2-[3-[4-(4-phenylphenyl)triazol-1-yl]propoxy]oxane-2-carboxylate	1427030: Binding affinity to human IgG1-fused Siglec-7-Fc assessed as inhibition of Siglec-7-Fc binding to RBC preincubated for 10 mins followed by RBC addition measured after 20 mins by FACS analysis	ic50	1.6000	uM
sodium (2R,4S,5R,6R)-5-acetamido-6-[(1R,2R)-1,2-dihydroxy-3-(methanesulfonamido)propyl]-4-hydroxy-2-[3-[4-(4-phenylphenyl)triazol-1-yl]propoxy]oxane-2-carboxylate	1427030: Binding affinity to human IgG1-fused Siglec-7-Fc assessed as inhibition of Siglec-7-Fc binding to RBC preincubated for 10 mins followed by RBC addition measured after 20 mins by FACS analysis	ic50	2.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Fonofos	increases methylation	1
Lead	decreases expression	1
Parathion	increases methylation	1
Tretinoin	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3607813	Binding	Binding affinity to human IgG1-fused human Siglec-7-FC (Gln19 to Gly357 residues) assessed as inhibition Siglec-7-Fc binding to to RBC pre-incubated for 10 mins before 20 mins incubation with RBCs by flow cytometry	Synthesis and biological evaluation of 9-N-oxamyl sialosides as Siglec-7 ligands. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D8G8	Ubigene H1 SIGLEC7 KO	Embryonic stem cell	Male

Clinical trials (associated diseases)

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