SIGLEC8

Summary

SIGLEC8 (sialic acid binding Ig like lectin 8, HGNC:10877) is a protein-coding gene on chromosome 19q13.41, encoding Sialic acid-binding Ig-like lectin 8 (Q9NYZ4). Putative adhesion molecule that mediates sialic-acid dependent binding to blood cells.

Sialic acid-binding immunoglobulin (Ig)-like lectins, or SIGLECs (e.g., CD33 (MIM 159590)), are a family of type 1 transmembrane proteins each having a unique expression pattern, mostly in hemopoietic cells. SIGLEC8 is a member of the CD33-like subgroup of SIGLECs, which are localized to 19q13.3-q13.4 and have 2 conserved cytoplasmic tyrosine-based motifs: an immunoreceptor tyrosine-based inhibitory motif, or ITIM (see MIM 604964), and a motif homologous to one identified in signaling lymphocyte activation molecule (SLAM; MIM 603492) that mediates an association with SLAM-associated protein (SAP; MIM 300490) (summarized by Foussias et al., 2000 [PubMed 11095983]).

Source: NCBI Gene 27181 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 89 total
• Druggable target: yes
• MANE Select transcript: NM_014442

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10877
Approved symbol	SIGLEC8
Name	sialic acid binding Ig like lectin 8
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	SIGLEC-8, SAF2, SIGLEC8L, MGC59785
Ensembl gene	ENSG00000105366
Ensembl biotype	protein_coding
OMIM	605639
Entrez	27181

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000321424, ENST00000340550, ENST00000430817, ENST00000597352, ENST00000853029, ENST00000960609, ENST00000960610, ENST00000960611

RefSeq mRNA: 2 — MANE Select: NM_014442 NM_001363548, NM_014442

CCDS: CCDS33086, CCDS86797

Canonical transcript exons

ENST00000321424 — 7 exons

Exon	Start	End
ENSE00001340748	51450997	51452633
ENSE00001371472	51457934	51458454
ENSE00002505130	51454219	51454315
ENSE00003472928	51457184	51457231
ENSE00003561049	51455418	51455687
ENSE00003655002	51457461	51457739
ENSE00003694269	51454684	51454780

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 76.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4468 / max 63.5416, expressed in 94 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182426	0.1833	51
182425	0.1792	59
182423	0.0510	14
182422	0.0210	9
182424	0.0124	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	76.89	gold quality
spinal cord	UBERON:0002240	74.56	gold quality
inferior olivary complex	UBERON:0002127	72.86	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	72.73	silver quality
triceps brachii	UBERON:0001509	72.21	gold quality
gluteal muscle	UBERON:0002000	72.07	gold quality
spleen	UBERON:0002106	70.89	gold quality
lymph node	UBERON:0000029	70.44	gold quality
myocardium	UBERON:0002349	70.25	gold quality
right adrenal gland cortex	UBERON:0035827	68.80	gold quality
left adrenal gland	UBERON:0001234	68.11	gold quality
substantia nigra	UBERON:0002038	67.88	gold quality
left adrenal gland cortex	UBERON:0035825	67.04	gold quality
midbrain	UBERON:0001891	66.62	gold quality
adrenal cortex	UBERON:0001235	66.34	gold quality
right adrenal gland	UBERON:0001233	65.17	gold quality
medial globus pallidus	UBERON:0002477	65.14	silver quality
pancreatic ductal cell	CL:0002079	65.12	silver quality
left ventricle myocardium	UBERON:0006566	64.75	gold quality
prefrontal cortex	UBERON:0000451	64.66	gold quality
cardiac muscle of right atrium	UBERON:0003379	64.43	gold quality
adrenal gland	UBERON:0002369	64.14	gold quality
parotid gland	UBERON:0001831	64.03	gold quality
gall bladder	UBERON:0002110	63.32	gold quality
globus pallidus	UBERON:0001875	62.92	silver quality
rectum	UBERON:0001052	62.91	gold quality
amygdala	UBERON:0001876	62.90	gold quality
type B pancreatic cell	CL:0000169	62.67	gold quality
quadriceps femoris	UBERON:0001377	62.55	gold quality
vastus lateralis	UBERON:0001379	62.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): OLIG2

miRNA regulators (miRDB)

41 targeting SIGLEC8, 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-3646	100.00	73.56	5283
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-4450	98.26	68.35	725

Literature-anchored findings (GeneRIF, showing 27)

• Sialic acid binding immunoglobulin-like lectin 8 (Siglec-8) cross-linking with antibodies rapidly generated caspase-3-like activity and reduced eosinophil viability through induction of apoptosis (PMID:12609831)
• Siglec-8 binds preferentially to a sLex structure bearing an additional sulfate ester on the galactose 6-hydroxyl (PMID:15563466)
• Siglec-8-induced apoptosis in eosinophils occurs through the sequential production of reactive oxygen species, followed by induction of mitochondrial injury and caspase cleavage. (PMID:16157303)
• IL-5 priming enhances Siglec-8-mediated mitochondrial and ROS-dependent eosinophil apoptosis and eliminates caspase dependence. (PMID:17690326)
• First reported inhibitory effects of Siglec engagement on human mast cells. (PMID:18036650)
• A review of the cytotoxic effects of natural anti-Siglec8 autoantibodies on both neutrophils and eosinophils. (PMID:18558361)
• REVIEW: Siglec-8 and Siglec-F function on human eosinophils, and Siglec-8 function on mast cells (PMID:19178537)
• Selective and specific engagement and binding of Siglec-8 on eosinophils by a synthetic 6’-sulfo-sLe(x)-containing ligand could be useful for controlling eosinophilic inflammatory responses in vivo. (PMID:19458105)
• The Siglec-8 gene may be a susceptibility locus for asthma. (PMID:20087405)
• expressed on eosinophils and basophils from subjects with chronic eosinophilic leukemia, chronic myelogenous leukemia, and on malignant and non-malignant bone marrow mast cells (PMID:21938510)
• Eosinophils primed by IL-33 and/or IL-5 in vivo would be expected to display enhanced susceptibility to undergoing Siglec-8-induced apoptosis. (PMID:22079334)
• Engagement of Siglec-8 on blood eosinophils results in caspase- and mitochondria-dependent apoptosis. (PMID:22324980)
• Report the development of a sensitive competitive ELISA to detect sSiglec-8 in human serum samples obtained from patients with various forms of eosinophilia. (PMID:22683541)
• In activated eosinophils ligation of Siglec-8 leads to ROS-dependent enhancement of IL-5-induced ERK phosphorylation, which results in a novel mode of biochemically regulated eosinophil cell death. (PMID:23684072)
• Siglec-8 expression is sensitive to tiotropium and formoterol, indicating that it may be involved in COPD pathogenesis and may influence COPD phenotyping (PMID:23835953)
• 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)
• Our study suggested that intratumoral Siglec-8 expression was an independent prognostic factor for overall survival of patients with gastric cancer (PMID:26883254)
• In differentiating ,eosinophils, SIGLEC-8 messenger RNA and protein were markedly down-regulated in parallel with OLIG2 by an OLIG2 small interfering RNA or a short hairpin RNA. An E-box in the first intron was found to stimulate SIGLEC-8 gene transcription and to bind OLIG2. (PMID:27154355)
• miR-215 acts in concert with the host gene IARS2 to affect neuron migration and proliferation through the target gene SIGLEC-8. (PMID:28006787)
• Targeting saporin to Siglec-8 consistently caused extensive cell death. (PMID:28734845)
• These data demonstrate that Siglec-8 functions uniquely as an activating receptor on IL-5-primed eosinophils through a novel pathway involving regulation of beta2-integrin-dependent adhesion, NADPH oxidase, and a subset of protein kinases (PMID:28888781)
• Siglec-8 is highly expressed on blood eosinophils from eosinophilic donors and normal donors and represents a potential therapeutic target for eosinophilic disorders (PMID:30543818)
• Promoter region single nucleotide polymorphism of siglec-8 gene associates with susceptibility to allergic asthma. (PMID:32077788)
• First Evidence for a Role of Siglec-8 in Breast Cancer. (PMID:33670444)
• Induction of the endogenous sialoglycan ligand for eosinophil death receptor Siglec-8 in chronic rhinosinusitis with hyperplastic nasal polyposis. (PMID:33755113)
• Sialylated keratan sulfates on MUC5B are Siglec-8 ligands in the human esophagus. (PMID:39173029)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Siglece	ENSMUSG00000030474
rattus_norvegicus	Siglec8	ENSRNOG00000022640

Paralogs (16): CD22 (ENSG00000012124), SIGLEC1 (ENSG00000088827), CD33 (ENSG00000105383), SIGLEC6 (ENSG00000105492), MAG (ENSG00000105695), SIGLEC9 (ENSG00000129450), 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 8 — Q9NYZ4 (reviewed: Q9NYZ4)

Alternative names: Sialoadhesin family member 2

All UniProt accessions (2): Q9NYZ4, C9JT30

UniProt curated annotations — full annotation on UniProt →

Function. Putative adhesion molecule that mediates sialic-acid dependent binding to blood cells. Preferentially binds to alpha-2,3-linked sialic acid. Also binds to 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. Recognizes simultaneously epitopes having a terminal N-acetylneuraminic acid (sialic acid) and an underlying 6-O-sulfated galactose. Preferentially binds to Gal-6-sulfated sialyl-Lewis X glycan epitopes.

Subcellular location. Membrane.

Tissue specificity. Expressed specifically on blood cells namely basophil, mast cells and eosinophils.

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 (3)

UniProt ID	Names	Canonical?
Q9NYZ4-1	1, Long	yes
Q9NYZ4-2	2
Q9NYZ4-3	3

RefSeq proteins (2): NP_001350477, NP_055257* (*=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
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051036	SIGLEC	Family

Pfam: PF00047, PF07686, PF13927

UniProt features (55 total): strand 12, mutagenesis site 7, binding site 4, disulfide bond 4, region of interest 3, glycosylation site 3, sequence variant 3, helix 3, turn 3, domain 3, short sequence motif 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7QU6	X-RAY DIFFRACTION	2.34
7QUH	X-RAY DIFFRACTION	2.87
7QUI	X-RAY DIFFRACTION	3.35
2N7A	SOLUTION NMR
2N7B	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYZ4-F1	74.39	0.51

Antibody-complex structures (SAbDab): 1 — 7QUH

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): 125 (indispensable role in 6’-sulfo sialyl-lewis x)

Ligand- & substrate-binding residues (4): 23; 72–75; 125; 134–138

Disulfide bonds (4): 42–181, 47–107, 175–224, 283–328

Glycosylation sites (3): 172, 249, 267

Mutagenesis-validated functional residues (7):

Position	Phenotype
72	strongly impaired binding to 6’-sulfo sialyl-lewis x.
74	modestly affected binding to 6’-sulfo sialyl-lewis x.
75	modestly affected binding to 6’-sulfo sialyl-lewis x.
125	abolishes binding to 6’-sulfo sialyl-lewis x.
132	strongly impaired binding to 6’-sulfo sialyl-lewis x.
136	strongly impaired binding to 6’-sulfo sialyl-lewis x.
138	minor effects on binding to 6’-sulfo sialyl-lewis x.

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: 39 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_ORGANIC_ACID_BINDING, MARTENS_TRETINOIN_RESPONSE_UP, KLEIN_TARGETS_OF_BCR_ABL1_FUSION, GOMF_SIALIC_ACID_BINDING, TAVAZOIE_METASTASIS, MIR3646, MIR5010_3P, MIR4777_5P, MIR4491, MIR4657, MIR4450, MIR6769B_5P, FAN_EMBRYONIC_CTX_BIG_GROUPS_MICROGLIA

GO Biological Process (2): cell adhesion (GO:0007155), signal transduction (GO:0007165)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), 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
cellular process	2
binding	2
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signaling receptor activity	1
carboxylic acid binding	1
carbohydrate derivative binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIGLEC8	IL5RA	Q01344	662
SIGLEC8	FCGR3B	O75015	629
SIGLEC8	FCGR3A	P08637	629
SIGLEC8	CCR3	P51677	608
SIGLEC8	SIGLEC15	Q6ZMC9	585
SIGLEC8	IL5	P05113	583
SIGLEC8	EPX	P11678	579
SIGLEC8	NCAM1	P13591	543
SIGLEC8	SH2D1A	O60880	531
SIGLEC8	SLAMF1	Q13291	531
SIGLEC8	CD300A	Q9UGN4	513
SIGLEC8	PTGDR2	Q9Y5Y4	507
SIGLEC8	RNASE2	P10153	506
SIGLEC8	IL33	O95760	506
SIGLEC8	RNASE3	P12724	505

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SIGLEC8	TFF1	psi-mi:“MI:0915”(physical association)	0.540
SIGLEC8	TFF1	psi-mi:“MI:0407”(direct interaction)	0.540
SIGLEC8	CD33	psi-mi:“MI:0915”(physical association)	0.400
MAG	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400
MXRA5	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC7	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400
CD33	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC8	SIGLEC10	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC8	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC8	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC9	SIGLEC8	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): TFF1 (Reconstituted Complex)

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

974 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51452629:GGTCC:G	acceptor_gain	1.0000
19:51452630:GTCC:G	acceptor_gain	1.0000
19:51452631:TCC:T	acceptor_gain	1.0000
19:51452632:CC:C	acceptor_gain	1.0000
19:51452632:CCC:C	acceptor_gain	1.0000
19:51452633:CC:C	acceptor_gain	1.0000
19:51452634:C:CA	acceptor_loss	1.0000
19:51452634:C:CC	acceptor_gain	1.0000
19:51452634:C:T	acceptor_gain	1.0000
19:51452635:T:A	acceptor_loss	1.0000
19:51452639:C:CT	acceptor_gain	1.0000
19:51452640:A:T	acceptor_gain	1.0000
19:51454312:CACT:C	acceptor_gain	1.0000
19:51454314:CT:C	acceptor_gain	1.0000
19:51454682:A:AC	donor_gain	1.0000
19:51454683:C:CC	donor_gain	1.0000
19:51457178:TCCTA:T	donor_loss	1.0000
19:51457179:CCTA:C	donor_loss	1.0000
19:51457180:CTACC:C	donor_loss	1.0000
19:51457181:TACCT:T	donor_loss	1.0000
19:51457182:A:T	donor_loss	1.0000
19:51457183:C:CG	donor_loss	1.0000
19:51458042:T:TA	donor_gain	1.0000
19:51454019:AGTG:A	donor_gain	0.9900
19:51454214:CTCA:C	donor_loss	0.9900
19:51454215:TCACC:T	donor_loss	0.9900
19:51454216:CA:C	donor_loss	0.9900
19:51454217:ACCTG:A	donor_loss	0.9900
19:51454218:C:T	donor_loss	0.9900
19:51454311:TCACT:T	acceptor_gain	0.9900

AlphaMissense

3185 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51458100:G:C	F96L	0.982
19:51458100:G:T	F96L	0.982
19:51458102:A:G	F96L	0.982
19:51458187:G:C	F67L	0.981
19:51458187:G:T	F67L	0.981
19:51458189:A:G	F67L	0.981
19:51458190:C:A	W66C	0.977
19:51458190:C:G	W66C	0.977
19:51458101:A:C	F96C	0.968
19:51458101:A:G	F96S	0.967
19:51458192:A:G	W66R	0.965
19:51458192:A:T	W66R	0.965
19:51457523:C:G	C224S	0.956
19:51457524:A:T	C224S	0.956
19:51455584:C:A	W295C	0.952
19:51455584:C:G	W295C	0.952
19:51458014:C:G	R125P	0.951
19:51458056:A:G	I111T	0.951
19:51457621:C:A	W191C	0.950
19:51457621:C:G	W191C	0.950
19:51455608:G:C	S287R	0.948
19:51455608:G:T	S287R	0.948
19:51455610:T:G	S287R	0.948
19:51457524:A:G	C224R	0.948
19:51458017:A:G	F124S	0.947
19:51458068:C:G	C107S	0.947
19:51458069:A:T	C107S	0.947
19:51458150:C:G	A80P	0.945
19:51458248:C:G	C47S	0.939
19:51458249:A:T	C47S	0.939

dbSNP variants (sampled 300 via entrez): RS1000008400 (19:51460065 T>A,G), RS1000195859 (19:51452521 T>C), RS1000496456 (19:51456699 G>A,C), RS1000607577 (19:51459520 GATGATGATGATGATGATT>G), RS1001137131 (19:51451105 T>C), RS1001288005 (19:51455588 C>G), RS1001778000 (19:51455349 C>T), RS1001891238 (19:51457326 C>G,T), RS1002220127 (19:51451345 A>T), RS1002807452 (19:51456206 C>T), RS1002836605 (19:51453095 G>T), RS1003188963 (19:51456536 G>T), RS1003349031 (19:51458480 C>T), RS1004220751 (19:51457382 C>T), RS1004230454 (19:51453813 G>A)

Disease associations

OMIM: gene MIM:605639 | 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: yes

ChEMBL targets (1): CHEMBL4630877 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — CD33-related SIGLECs

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
vanadyl sulfate	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Ozone	affects expression, increases abundance	1
Valproic Acid	increases methylation	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_E6RR	Genomeditech CHO-K1 H_SIGLEC8	Spontaneously immortalized cell line	Female
CVCL_E6UV	Genomeditech HEK-293 H_SIGLEC8	Transformed cell line	Female

Clinical trials (associated diseases)

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