SIGLEC11

Summary

SIGLEC11 (sialic acid binding Ig like lectin 11, HGNC:15622) is a protein-coding gene on chromosome 19q13.33, encoding Sialic acid-binding Ig-like lectin 11 (Q96RL6). Putative adhesion molecule that mediates sialic-acid dependent binding to cells.

This gene encodes a member of the sialic acid-binding immunoglobulin-like lectin family. These cell surface lectins are characterized by structural motifs in the immunoglobulin (Ig)-like domains and sialic acid recognition sites in the first Ig V set domain. This family member mediates anti-inflammatory and immunosuppressive signaling. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 114132 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 167 total
• MANE Select transcript: NM_052884

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15622
Approved symbol	SIGLEC11
Name	sialic acid binding Ig like lectin 11
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000161640
Ensembl biotype	protein_coding
OMIM	607157
Entrez	114132

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000426296, ENST00000426971, ENST00000447370, ENST00000959925, ENST00000959926

RefSeq mRNA: 2 — MANE Select: NM_052884 NM_001135163, NM_052884

CCDS: CCDS12790, CCDS46150

Canonical transcript exons

ENST00000447370 — 11 exons

Exon	Start	End
ENSE00001059388	49960552	49960935
ENSE00001231864	49961006	49961172
ENSE00001633597	49958283	49958570
ENSE00001697661	49952298	49952394
ENSE00001834093	49948985	49950236
ENSE00002440716	49959030	49959077
ENSE00002444306	49959360	49959623
ENSE00002483239	49960137	49960421
ENSE00002491488	49958643	49958900
ENSE00002534318	49959773	49959820
ENSE00003589909	49951891	49951972

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 92.99.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	92.99	gold quality
left ovary	UBERON:0002119	92.18	gold quality
right ovary	UBERON:0002118	89.80	gold quality
ovary	UBERON:0000992	86.10	gold quality
spleen	UBERON:0002106	85.47	gold quality
right adrenal gland	UBERON:0001233	84.97	gold quality
right adrenal gland cortex	UBERON:0035827	84.91	gold quality
adrenal gland	UBERON:0002369	82.73	gold quality
left adrenal gland cortex	UBERON:0035825	82.58	gold quality
left adrenal gland	UBERON:0001234	82.49	gold quality
adrenal cortex	UBERON:0001235	82.03	gold quality
body of stomach	UBERON:0001161	76.18	gold quality
stomach	UBERON:0000945	74.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.64	gold quality
monocyte	CL:0000576	70.87	gold quality
leukocyte	CL:0000738	70.29	gold quality
tendon of biceps brachii	UBERON:0008188	69.75	gold quality
fundus of stomach	UBERON:0001160	68.54	gold quality
body of pancreas	UBERON:0001150	67.28	gold quality
vermiform appendix	UBERON:0001154	65.19	gold quality
parotid gland	UBERON:0001831	64.66	gold quality
granulocyte	CL:0000094	64.19	gold quality
cardia of stomach	UBERON:0001162	63.89	silver quality
decidua	UBERON:0002450	62.61	silver quality
apex of heart	UBERON:0002098	62.56	gold quality
caecum	UBERON:0001153	62.33	gold quality
myocardium	UBERON:0002349	61.55	gold quality
superficial temporal artery	UBERON:0001614	59.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	59.87	gold quality
smooth muscle tissue	UBERON:0001135	59.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting SIGLEC11, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-10A-5P	98.89	69.85	712

Literature-anchored findings (GeneRIF, showing 7)

• cloning and characterization; a recently evolved signaling that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages including brain microglia (PMID:11986327)
• expressed in human but not in chimpanzee brain microglia; findings indicate that human SIGLEC11 emerged through human-specific gene conversion by an adjacent pseudogene (PMID:16151003)
• SIGLEC16 encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpart SIGLEC11 and has functional and non-functional alleles in humans. (PMID:18629938)
• Siglec-11 ectopically expressed on murine microglia interacts with PSA on neurons, reduces LPS-induced gene transcription of proinflammatory mediators, impairs phagocytosis and alleviates microglial neurotoxicity. (PMID:20203208)
• The results indicate potential roles for Siglec-11 in ovarian physiology and human evolution. (PMID:21467073)
• The authors demonstrated that the human-specific pathogen Escherichia coli K1 uses its polysialic acid capsule as a molecular mimic to engage Siglec-11 and escape killing. In contrast, engagement of the activating counterpart Siglec-16 increases elimination of bacteria. (PMID:28100677)
• Human-specific microglial Siglec-11 transcript variant has the potential to affect polysialic acid-mediated brain functions at a distance. (PMID:32845322)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Siglecg	ENSMUSG00000030468
rattus_norvegicus	Siglec10	ENSRNOG00000037339

Paralogs (16): CD22 (ENSG00000012124), SIGLEC1 (ENSG00000088827), SIGLEC8 (ENSG00000105366), CD33 (ENSG00000105383), SIGLEC6 (ENSG00000105492), MAG (ENSG00000105695), SIGLEC9 (ENSG00000129450), SIGLEC10 (ENSG00000142512), TMEM25 (ENSG00000149582), SIGLEC16 (ENSG00000161643), SIGLEC7 (ENSG00000168995), SIGLECL1 (ENSG00000179213), SIGLEC15 (ENSG00000197046), SIGLEC14 (ENSG00000254415), SIGLEC12 (ENSG00000254521), SIGLEC5 (ENSG00000268500)

Protein

Protein identifiers

Sialic acid-binding Ig-like lectin 11 — Q96RL6 (reviewed: Q96RL6)

All UniProt accessions (2): Q96RL6, H7C2S0

UniProt curated annotations — full annotation on UniProt →

Function. Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,8-linked sialic acid. 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.

Subunit / interactions. Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation.

Subcellular location. Membrane.

Tissue specificity. Expressed by macrophages in various tissues including Kupffer cells. Also found in brain microglia.

Post-translational modifications. Phosphorylated on tyrosine residues.

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?
Q96RL6-1	1	yes
Q96RL6-2	2

RefSeq proteins (2): NP_001128635, NP_443116* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003006	Ig/MHC_CS	Conserved_site
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051036	SIGLEC	Family

Pfam: PF07679, PF07686, PF13927

UniProt features (29 total): glycosylation site 7, disulfide bond 5, domain 4, region of interest 2, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, short sequence motif 1, binding site 1, modified residue 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RL6-F1	74.81	0.39

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): 132

Post-translational modifications (1): 668

Disulfide bonds (5): 49–186, 54–114, 177–228, 287–334, 391–436

Glycosylation sites (7): 55, 90, 262, 366, 375, 497, 515

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: 41 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOMF_PHOSPHATASE_BINDING, GOMF_ORGANIC_ACID_BINDING, GOMF_SIALIC_ACID_BINDING, H1_6_TARGET_GENES, MIR616_5P, MIR371B_5P, MIR373_5P, MIR4284, CDH4_TARGET_GENES, GAO_LARGE_INTESTINE_24W_C11_PANETH_LIKE_CELL, BUSSLINGER_GASTRIC_PARIETAL_CELLS, DESCARTES_MAIN_FETAL_PARIETAL_AND_CHIEF_CELLS, DESCARTES_FETAL_CEREBELLUM_MICROGLIA, DESCARTES_FETAL_CEREBRUM_MICROGLIA

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

GO Molecular Function (3): phosphatase binding (GO:0019902), carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691)

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	1
enzyme binding	1
binding	1
carboxylic acid binding	1
carbohydrate derivative binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

802 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIGLEC11	PTPN11	Q06124	806
SIGLEC11	SIGLEC15	Q6ZMC9	595
SIGLEC11	NRCAM	Q92823	549
SIGLEC11	SELPLG	Q14242	498
SIGLEC11	TYROBP	O43914	479
SIGLEC11	CD200R1	Q8TD46	469
SIGLEC11	NCAM1	P13591	469
SIGLEC11	SIGLEC14	Q08ET2	447
SIGLEC11	CD200	P41217	438
SIGLEC11	HAVCR2	Q8TDQ0	425
SIGLEC11	AOC3	Q16853	314
SIGLEC11	STUM	Q69YW2	311
SIGLEC11	ST6GAL1	P15907	306
SIGLEC11	SPDYE3	A6NKU9	305
SIGLEC11	MORN5	Q5VZ52	288

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SIGLEC11	tsf	psi-mi:“MI:0915”(physical association)	0.000
SIGLEC11		psi-mi:“MI:0915”(physical association)	0.000
	SIGLEC11	psi-mi:“MI:0915”(physical association)	0.000
SIGLEC11	rne	psi-mi:“MI:0915”(physical association)	0.000
SIGLEC11	mdtB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): LGALS3BP (Reconstituted Complex), PTPN6 (Affinity Capture-Western), PTPN11 (Affinity Capture-Western)

ESM2 similar proteins: A6NMB1, A7LCJ3, G1T7E7, G1TR84, M3XWH1, O15389, O43699, O70540, P04217, P05362, P0DP72, P13597, P20138, P32942, P33729, Q00238, Q08ET2, Q14773, Q28125, Q28730, Q28806, Q2KJF1, Q5NKT8, Q5NKU6, Q5NKV4, Q5NKV6, Q5NKV9, Q60625, Q62230, Q64JA4, Q6DN72, Q7L513, Q80ZE3, Q91Y57, Q920A9, Q920G3, Q92154, Q95132, Q95LH0, Q96A28

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	131
Likely benign	22
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1686 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49950039:T:TA	donor_gain	1.0000
19:49951885:TCTCA:T	donor_loss	1.0000
19:49951886:CTCA:C	donor_loss	1.0000
19:49951887:TCAC:T	donor_loss	1.0000
19:49951887:TCACC:T	donor_loss	1.0000
19:49951888:CACC:C	donor_loss	1.0000
19:49951888:CACCT:C	donor_loss	1.0000
19:49958277:CCTCA:C	donor_loss	1.0000
19:49958278:CTCA:C	donor_loss	1.0000
19:49958279:TCA:T	donor_loss	1.0000
19:49958280:CA:C	donor_loss	1.0000
19:49958282:C:CA	donor_loss	1.0000
19:49958710:T:A	donor_gain	1.0000
19:49960135:A:AC	donor_gain	1.0000
19:49960135:ACAGG:A	donor_gain	1.0000
19:49960136:C:CC	donor_gain	1.0000
19:49960136:CAGGC:C	donor_gain	1.0000
19:49950235:CC:C	acceptor_gain	0.9900
19:49950236:CC:C	acceptor_gain	0.9900
19:49951889:A:AC	donor_gain	0.9900
19:49951890:C:CC	donor_gain	0.9900
19:49951922:T:TA	donor_gain	0.9900
19:49951969:CACC:C	acceptor_gain	0.9900
19:49951970:ACCC:A	acceptor_loss	0.9900
19:49951971:CC:C	acceptor_gain	0.9900
19:49951972:CC:C	acceptor_gain	0.9900
19:49951972:CCTGA:C	acceptor_loss	0.9900
19:49951973:C:CA	acceptor_loss	0.9900
19:49951973:C:CC	acceptor_gain	0.9900
19:49951973:CTGAG:C	acceptor_loss	0.9900

AlphaMissense

4500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49960703:G:C	F103L	0.991
19:49960703:G:T	F103L	0.991
19:49960705:A:G	F103L	0.991
19:49960793:C:A	W73C	0.990
19:49960793:C:G	W73C	0.990
19:49959520:C:A	W299C	0.989
19:49959520:C:G	W299C	0.989
19:49960303:C:A	W193C	0.988
19:49960303:C:G	W193C	0.988
19:49960704:A:C	F103C	0.985
19:49960790:G:C	F74L	0.984
19:49960790:G:T	F74L	0.984
19:49960792:A:G	F74L	0.984
19:49959522:A:G	W299R	0.983
19:49959522:A:T	W299R	0.983
19:49959403:G:C	N338K	0.981
19:49959403:G:T	N338K	0.981
19:49960305:A:G	W193R	0.980
19:49960305:A:T	W193R	0.980
19:49960352:C:T	C177Y	0.979
19:49960795:A:G	W73R	0.979
19:49960795:A:T	W73R	0.979
19:49960200:A:G	C228R	0.978
19:49960353:A:G	C177R	0.978
19:49960704:A:G	F103S	0.978
19:49960199:C:G	C228S	0.977
19:49960200:A:T	C228S	0.977
19:49960665:A:G	L116S	0.976
19:49960351:A:C	C177W	0.975
19:49958797:C:A	W403C	0.974

dbSNP variants (sampled 300 via entrez): RS1000020352 (19:49958116 T>C), RS1000088091 (19:49955463 A>C), RS1000257919 (19:49952223 T>C,G), RS1000767382 (19:49957207 C>T), RS1001366895 (19:49962981 G>T), RS1001612758 (19:49957408 C>A,T), RS1001730307 (19:49952137 C>T), RS1001730685 (19:49952156 G>A,T), RS1001795398 (19:49962813 G>A), RS1002584682 (19:49956271 A>G), RS1002590992 (19:49962107 G>A), RS1002768916 (19:49950804 A>G), RS1002778107 (19:49961956 A>G), RS1003022309 (19:49956093 G>T), RS1003544681 (19:49961227 C>A,G)

Disease associations

OMIM: gene MIM:607157 | 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
GCST004747_4	Lung cancer in never smokers	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation	2
aristolochic acid I	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
2-palmitoylglycerol	increases expression	1
Allergens	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Phthalic Acids	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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