SIGLEC14

Summary

SIGLEC14 (sialic acid binding Ig like lectin 14, HGNC:32926) is a protein-coding gene on chromosome 19q13.41, encoding Sialic acid-binding Ig-like lectin 14 (Q08ET2). Putative adhesion molecule.

Predicted to enable sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to be located in ficolin-1-rich granule membrane and tertiary granule membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 100049587 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 61 total
• Druggable target: yes
• MANE Select transcript: NM_001098612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32926
Approved symbol	SIGLEC14
Name	sialic acid binding Ig like lectin 14
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000254415
Ensembl biotype	protein_coding
OMIM	618132
Entrez	100049587

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000360844, ENST00000533866

RefSeq mRNA: 1 — MANE Select: NM_001098612 NM_001098612

CCDS: CCDS42604

Canonical transcript exons

ENST00000360844 — 7 exons

Exon	Start	End
ENSE00001411414	51645477	51645530
ENSE00001751585	51639478	51643397
ENSE00001793190	51646723	51646825
ENSE00002486219	51645782	51646060
ENSE00003488908	51643537	51643672
ENSE00003571355	51643779	51644036
ENSE00003635060	51646257	51646640

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 93.41.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	93.41	gold quality
monocyte	CL:0000576	92.96	gold quality
leukocyte	CL:0000738	92.67	gold quality
vermiform appendix	UBERON:0001154	89.88	gold quality
bone marrow cell	CL:0002092	89.06	gold quality
bone marrow	UBERON:0002371	88.77	gold quality
spleen	UBERON:0002106	86.35	gold quality
granulocyte	CL:0000094	85.33	gold quality
upper lobe of left lung	UBERON:0008952	77.32	gold quality
right lung	UBERON:0002167	76.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.72	gold quality
lymph node	UBERON:0000029	74.61	gold quality
lung	UBERON:0002048	74.06	gold quality
right adrenal gland cortex	UBERON:0035827	71.86	gold quality
placenta	UBERON:0001987	71.40	gold quality
gall bladder	UBERON:0002110	70.59	gold quality
right adrenal gland	UBERON:0001233	70.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.68	gold quality
urinary bladder	UBERON:0001255	68.42	gold quality
left uterine tube	UBERON:0001303	68.39	gold quality
right coronary artery	UBERON:0001625	68.35	gold quality
smooth muscle tissue	UBERON:0001135	67.86	gold quality
tonsil	UBERON:0002372	66.95	gold quality
left adrenal gland	UBERON:0001234	66.71	gold quality
small intestine	UBERON:0002108	66.36	gold quality
adrenal gland	UBERON:0002369	66.01	gold quality
left adrenal gland cortex	UBERON:0035825	65.98	gold quality
left coronary artery	UBERON:0001626	65.43	gold quality
omental fat pad	UBERON:0010414	65.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	64.91	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	33.35
E-MTAB-6678	yes	24.26
E-ANND-3	yes	18.81
E-CURD-112	yes	13.53
E-MTAB-9801	yes	6.69
E-GEOD-70580	no	39.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting SIGLEC14, 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-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-486-3P	99.51	66.82	1901

Literature-anchored findings (GeneRIF, showing 12)

• Siglec-14 and Siglec-5 appear to be the first glycan binding paired receptors. Near-complete sequence identity of the amino-terminal part of human Siglec-14 and Siglec-5 indicates partial gene conversion between SIGLEC14 and SIGLEC5. (PMID:17012248)
• The presence of the “SIGLEC14 null” allele in all human populations we tested implies an ancient origin, while its allelic frequency is higher in Asians compared with Africans and Europeans. Siglec-14 may play some role in bacterial infection. (PMID:19369701)
• Siglec-14 and its downstream signaling pathway facilitate the “infection-inflammation-exacerbation” axis of COPD disease progression (PMID:23519826)
• Data indicate that the Siglec-5/14 genotype influences neutrophil responses to group B Streptococcus. (PMID:24799499)
• Genome-wide association analyses revealed common DNA variants in PLG, LPA, and near SIGLEC14 that contribute to plasma plasminogen level variation. (PMID:25208887)
• An unbiased screen revealed Hsp70 as a ligand for Siglec-5 and Siglec-14. Hsp70 stimulation through Siglec-5 delivers an anti-inflammatory signal, while stimulation through Siglec-14 is pro-inflammatory. (PMID:26459514)
• SIGLEC14 expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• Demonstrate an association between SIGLEC14 expression and clinical tuberculosis, mycobacterium tuberculosis replication, and BCG-specific T-cell cytokine production. (PMID:28454648)
• soluble Siglec-14 suppresses pro-inflammatory responses triggered by membrane-bound Siglec-14 (PMID:30377253)
• Siglec-14 Enhances NLRP3-Inflammasome Activation in Macrophages. (PMID:31805552)
• Analysis of Genetic Variants Associated with Levels of Immune Modulating Proteins for Impact on Alzheimer’s Disease Risk Reveal a Potential Role for SIGLEC14. (PMID:34208838)
• Genes ACOT1, GSTM1, SIGLEC14 and UGT2B17 are identified as highly absent genes in gastric cancer population. (PMID:36109518)

Cross-species orthologs

0 orthologs

Paralogs (16): CD22 (ENSG00000012124), SIGLEC1 (ENSG00000088827), SIGLEC8 (ENSG00000105366), CD33 (ENSG00000105383), SIGLEC6 (ENSG00000105492), MAG (ENSG00000105695), SIGLEC9 (ENSG00000129450), SIGLEC10 (ENSG00000142512), TMEM25 (ENSG00000149582), SIGLEC11 (ENSG00000161640), SIGLEC16 (ENSG00000161643), SIGLEC7 (ENSG00000168995), SIGLECL1 (ENSG00000179213), SIGLEC15 (ENSG00000197046), SIGLEC12 (ENSG00000254521), SIGLEC5 (ENSG00000268500)

Protein

Protein identifiers

Sialic acid-binding Ig-like lectin 14 — Q08ET2 (reviewed: Q08ET2)

All UniProt accessions (1): Q08ET2

UniProt curated annotations — full annotation on UniProt →

Function. Putative adhesion molecule. Sialic acid-binding paired receptor which may activate associated receptors.

Subunit / interactions. Interacts with TYROBP.

Subcellular location. Cell membrane.

Tissue specificity. Mainly expressed in hematopoietic tissues including bone marrow, spleen and fetal liver. Also detected in lung and testis.

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

RefSeq proteins (1): NP_001092082* (*=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
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051036	SIGLEC	Family

Pfam: PF07686, PF08205, PF13895

UniProt features (14 total): domain 3, disulfide bond 2, topological domain 2, signal peptide 1, chain 1, glycosylation site 1, mutagenesis site 1, transmembrane region 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q08ET2-F1	83.87	0.51

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): 119

Disulfide bonds (2): 164–213, 274–319

Glycosylation sites (1): 231

Mutagenesis-validated functional residues (1):

Position	Phenotype
362	loss of interaction with tyrobp.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-2172127	DAP12 interactions
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 55 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOCC_SECRETORY_VESICLE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOMF_ORGANIC_ACID_BINDING, GOCC_TERTIARY_GRANULE, GOCC_TERTIARY_GRANULE_MEMBRANE, GOCC_FICOLIN_1_RICH_GRANULE, GOCC_FICOLIN_1_RICH_GRANULE_MEMBRANE, GOMF_SIALIC_ACID_BINDING, REACTOME_DAP12_INTERACTIONS, REACTOME_NEUTROPHIL_DEGRANULATION, SKIL_TARGET_GENES, ZNF768_TARGET_GENES, MIR616_5P

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

GO Molecular Function (2): carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691)

GO Cellular Component (4): plasma membrane (GO:0005886), tertiary granule membrane (GO:0070821), ficolin-1-rich granule membrane (GO:0101003), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	2
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
secretory granule membrane	2
tertiary granule	2
cellular process	1
binding	1
carboxylic acid binding	1
carbohydrate derivative binding	1
membrane	1
cell periphery	1
ficolin-1-rich granule	1
cellular anatomical structure	1

Protein interactions and networks

STRING

932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIGLEC14	TYROBP	O43914	991
SIGLEC14	SYK	P43405	604
SIGLEC14	SIGLEC15	Q6ZMC9	525
SIGLEC14	ST6GAL1	P15907	507
SIGLEC14	HCST	Q9UBK5	498
SIGLEC14	EEF1A2	P54266	476
SIGLEC14	ST6GALNAC1	Q9NSC7	449
SIGLEC14	SIGLEC11	Q96RL6	447
SIGLEC14	NEU2	Q9Y3R4	438
SIGLEC14	CD274	Q9NZQ7	430
SIGLEC14	CEACAM3	P40198	426
SIGLEC14	RENBP	P51606	418
SIGLEC14	ST6GALNAC5	Q9BVH7	411
SIGLEC14	ST6GALNAC2	Q9UJ37	410
SIGLEC14	SIGLEC5	O15389	408

IntAct

13 interactions, top by confidence:

A	B	Type	Score
SIGLEC14	TYROBP	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC14	LILRB2	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC14	CD33	psi-mi:“MI:0915”(physical association)	0.400
CD300LB	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400
FCAR	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400
IFNGR1	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400
LILRB2	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400
CD33	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC14	IFNGR1	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC15	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC14	SIGLEC5	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC8	SIGLEC14	psi-mi:“MI:0915”(physical association)	0.400

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1243 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51643778:CT:C	donor_gain	1.0000
19:51645471:TCCTA:T	donor_loss	1.0000
19:51645472:CCTA:C	donor_loss	1.0000
19:51645472:CCTAC:C	donor_loss	1.0000
19:51645473:CTA:C	donor_loss	1.0000
19:51645474:TA:T	donor_loss	1.0000
19:51645475:A:AT	donor_loss	1.0000
19:51646304:T:TA	donor_gain	1.0000
19:51646305:C:A	donor_gain	1.0000
19:51646309:T:A	donor_gain	1.0000
19:51646336:T:TA	donor_gain	1.0000
19:51646337:C:A	donor_gain	1.0000
19:51646721:ACC:A	donor_gain	1.0000
19:51646721:ACCC:A	donor_gain	1.0000
19:51646721:ACCCC:A	donor_gain	1.0000
19:51646722:CCC:C	donor_gain	1.0000
19:51646722:CCCC:C	donor_gain	1.0000
19:51646722:CCCCC:C	donor_gain	1.0000
19:51643534:CACC:C	donor_loss	0.9900
19:51643535:ACCTG:A	donor_loss	0.9900
19:51643536:CCTGG:C	donor_loss	0.9900
19:51643669:CTTC:C	acceptor_gain	0.9900
19:51643670:TTC:T	acceptor_gain	0.9900
19:51643670:TTCC:T	acceptor_loss	0.9900
19:51643673:C:CC	acceptor_gain	0.9900
19:51643673:C:CG	acceptor_loss	0.9900
19:51643673:C:G	acceptor_loss	0.9900
19:51643778:CTCTG:C	donor_gain	0.9900
19:51643850:C:A	donor_gain	0.9900
19:51643922:C:A	donor_gain	0.9900

AlphaMissense

2538 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51646408:G:C	F90L	0.974
19:51646408:G:T	F90L	0.974
19:51646410:A:G	F90L	0.974
19:51646409:A:C	F90C	0.965
19:51645942:C:A	W180C	0.960
19:51645942:C:G	W180C	0.960
19:51646549:G:C	F43L	0.960
19:51646549:G:T	F43L	0.960
19:51646551:A:G	F43L	0.960
19:51646498:C:A	W60C	0.958
19:51646498:C:G	W60C	0.958
19:51643575:G:C	F370L	0.951
19:51643575:G:T	F370L	0.951
19:51643577:A:G	F370L	0.951
19:51646409:A:G	F90S	0.949
19:51645944:A:G	W180R	0.947
19:51645944:A:T	W180R	0.947
19:51645991:C:G	C164S	0.945
19:51645992:A:T	C164S	0.945
19:51646376:C:G	C101S	0.943
19:51646377:A:T	C101S	0.943
19:51645844:C:G	C213S	0.942
19:51645845:A:T	C213S	0.942
19:51646500:A:G	W60R	0.942
19:51646500:A:T	W60R	0.942
19:51646495:G:C	F61L	0.938
19:51646495:G:T	F61L	0.938
19:51646497:A:G	F61L	0.938
19:51645845:A:G	C213R	0.936
19:51643933:C:A	W286C	0.934

dbSNP variants (sampled 300 via entrez): RS1000272286 (19:51647143 G>T), RS1001721362 (19:51648752 C>T), RS1002001968 (19:51647764 G>A,T), RS1002223027 (19:51642220 G>A), RS1002572536 (19:51641625 G>A), RS1003010105 (19:51648730 T>C), RS1003508337 (19:51642026 C>A), RS1004070106 (19:51641776 C>T), RS1004399331 (19:51641252 C>T), RS1004583182 (19:51647657 T>A), RS1005337455 (19:51648262 G>T), RS1005352635 (19:51642408 G>A), RS1006512691 (19:51644735 G>A), RS1006517489 (19:51640746 G>A), RS1006529767 (19:51644332 C>G,T)

Disease associations

OMIM: gene MIM:618132 | 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
GCST002601_3	Plasma plasminogen levels	8.000000e-09
GCST006585_507	Blood protein levels	3.000000e-28

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006309	plasma plasminogen measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523280 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Cisplatin	increases expression	1
Methapyrilene	increases methylation	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4368160	Binding	Binding affinity to recombinant human Fc-fused siglec-14 by fluorescence based glycan microarray analysis	Expedient assembly of Oligo-LacNAcs by a sugar nucleotide regeneration system: Finding the role of tandem LacNAc and sialic acid position towards siglec binding. — Eur J Med Chem

Clinical trials (associated diseases)

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