SIGLEC12

Summary

SIGLEC12 (sialic acid binding Ig like lectin 12, HGNC:15482) is a protein-coding gene on chromosome 19q13.41, encoding Sialic acid-binding Ig-like lectin 12 (Q96PQ1). Putative adhesion molecule that mediates sialic-acid dependent binding to cells.

Sialic acid-binding immunoglobulin-like lectins (SIGLECs) are a family of cell surface proteins belonging to the immunoglobulin superfamily. They mediate protein-carbohydrate interactions by selectively binding to different sialic acid moieties present on glycolipids and glycoproteins. This gene encodes a member of the SIGLEC3-like subfamily of SIGLECs. Members of this subfamily are characterized by an extracellular V-set immunoglobulin-like domain followed by two C2-set immunoglobulin-like domains, and the cytoplasmic tyrosine-based motifs ITIM and SLAM-like. The encoded protein, upon tyrosine phosphorylation, has been shown to recruit the Src homology 2 domain-containing protein-tyrosine phosphatases SHP1 and SHP2. It has been suggested that the protein is involved in the negative regulation of macrophage signaling by functioning as an inhibitory receptor. This gene is located in a cluster with other SIGLEC3-like genes on 19q13.4. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 89858 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 161 total
• MANE Select transcript: NM_053003

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15482
Approved symbol	SIGLEC12
Name	sialic acid binding Ig like lectin 12
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	SLG, S2V, Siglec-XII, Siglec-12, Siglec-L1
Ensembl gene	ENSG00000254521
Ensembl biotype	protein_coding
OMIM	606094
Entrez	89858

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000291707, ENST00000596742, ENST00000598614, ENST00000942370

RefSeq mRNA: 3 — MANE Select: NM_053003 NM_001412258, NM_033329, NM_053003

CCDS: CCDS12833, CCDS59416

Canonical transcript exons

ENST00000291707 — 8 exons

Exon	Start	End
ENSE00001051311	51499920	51500300
ENSE00001222390	51491227	51491829
ENSE00001222398	51501307	51501800
ENSE00003463238	51498018	51498287
ENSE00003464456	51497349	51497445
ENSE00003549474	51496880	51496976
ENSE00003613261	51499170	51499217
ENSE00003687633	51499438	51499716

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 82.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1643 / max 265.8669, expressed in 145 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182431	1.0586	130
182430	0.0580	23
182432	0.0385	17
182433	0.0093	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	82.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.36	gold quality
duodenum	UBERON:0002114	74.96	gold quality
granulocyte	CL:0000094	73.92	gold quality
vermiform appendix	UBERON:0001154	72.15	gold quality
lymph node	UBERON:0000029	67.81	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.44	gold quality
small intestine	UBERON:0002108	65.26	gold quality
leukocyte	CL:0000738	63.01	gold quality
right lung	UBERON:0002167	62.74	gold quality
rectum	UBERON:0001052	62.44	gold quality
monocyte	CL:0000576	62.09	gold quality
blood	UBERON:0000178	59.77	gold quality
upper lobe of left lung	UBERON:0008952	59.38	gold quality
bone marrow cell	CL:0002092	58.65	silver quality
gall bladder	UBERON:0002110	58.43	gold quality
left adrenal gland cortex	UBERON:0035825	58.14	gold quality
bone marrow	UBERON:0002371	57.88	gold quality
left adrenal gland	UBERON:0001234	57.11	gold quality
lung	UBERON:0002048	56.80	gold quality
right adrenal gland cortex	UBERON:0035827	55.15	gold quality
adrenal gland	UBERON:0002369	54.51	gold quality
right adrenal gland	UBERON:0001233	54.12	gold quality
transverse colon	UBERON:0001157	53.97	gold quality
intestine	UBERON:0000160	53.22	gold quality
tonsil	UBERON:0002372	51.37	gold quality
liver	UBERON:0002107	50.17	gold quality
descending thoracic aorta	UBERON:0002345	49.74	gold quality
colonic epithelium	UBERON:0000397	49.39	gold quality
placenta	UBERON:0001987	49.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting SIGLEC12, 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-432-3P	100.00	67.86	705
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-8082	99.95	67.27	1170
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-3919	99.87	69.45	2489
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-130A-5P	99.33	70.26	2623
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-3925-5P	99.21	67.90	1466
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-6074	98.89	69.64	2187
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-4509	96.19	65.80	900

Literature-anchored findings (GeneRIF, showing 3)

• SIGLEC12, a human-specific segregating (pseudo)gene, encodes a signaling molecule expressed in prostate carcinomas. (PMID:21555517)
• cardiovascular outcomes may differ based on SIGLEC12 genotype, and antihypertensive treatment strategy. (PMID:23690342)
• Human-specific elimination of epithelial Siglec-XII suppresses the risk of inflammation-driven colorectal cancers. (PMID:38990656)

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), SIGLEC7 (ENSG00000168995), SIGLECL1 (ENSG00000179213), SIGLEC15 (ENSG00000197046), SIGLEC14 (ENSG00000254415), SIGLEC5 (ENSG00000268500)

Protein

Protein identifiers

Sialic acid-binding Ig-like lectin 12 — Q96PQ1 (reviewed: Q96PQ1)

Alternative names: Sialic acid-binding Ig-like lectin-like 1

All UniProt accessions (2): Q96PQ1, M0QYF3

UniProt curated annotations — full annotation on UniProt →

Function. Putative adhesion molecule that mediates sialic-acid dependent binding to cells. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface.

Subcellular location. Membrane.

Tissue specificity. Isoform Short is highly expressed in spleen, small intestine and adrenal gland; it is lower expressed in thyroid, placenta, brain, stomach, bone marrow, spinal cord and breast. Isoform Long is highly expressed in spleen, small intestine and bone marrow; it is lower expressed in thyroid, placenta, thymus, trachea, stomach, lung, adrenal gland, fetal brain and testis.

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?
Q96PQ1-1	Long, SLG-L	yes
Q96PQ1-2	Short, SLG-S

RefSeq proteins (3): NP_001399187, NP_201586, NP_443729* (*=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, PF13927

UniProt features (38 total): sequence variant 10, glycosylation site 7, disulfide bond 5, domain 4, short sequence motif 2, modified residue 2, topological domain 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PQ1-F1	75.98	0.36

Functional residue map

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

Post-translational modifications (2): 565, 588

Disulfide bonds (5): 44–104, 166–299, 171–231, 293–342, 401–446

Glycosylation sites (7): 140, 179, 230, 290, 360, 367, 385

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: 34 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MUELLER_PLURINET, BROWN_MYELOID_CELL_DEVELOPMENT_UP, GOMF_ORGANIC_ACID_BINDING, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_DN, GOMF_SIALIC_ACID_BINDING, E2F5_TARGET_GENES, MAFG_TARGET_GENES, ZNF274_TARGET_GENES, MIR8065, MIR138_5P, MIR7113_5P, MIR3925_5P, MIR3659, MIR4509

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

GO Molecular Function (3): 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
binding	2
cellular process	1
carboxylic acid binding	1
carbohydrate derivative binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIGLEC12	EIF1	P41567	529
SIGLEC12	TMEM97	Q5BJF2	519
SIGLEC12	GCDH	Q92947	477
SIGLEC12	AKAP17A	Q02040	444
SIGLEC12	ST6GAL1	P15907	443
SIGLEC12	SIAE	Q9HAT2	438
SIGLEC12	SIGLEC1	Q9BZZ2	419
SIGLEC12	ST6GALNAC2	Q9UJ37	418
SIGLEC12	SIGLEC15	Q6ZMC9	418
SIGLEC12	ST6GALNAC1	Q9NSC7	405
SIGLEC12	ST3GAL2	Q16842	398
SIGLEC12	ST6GALNAC5	Q9BVH7	398
SIGLEC12	EIF2S3	P41091	395
SIGLEC12	NEU2	Q9Y3R4	393
SIGLEC12	EIF5	P55010	380

IntAct

48 interactions, top by confidence:

A	B	Type	Score
PLPP6	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
PPGB	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
CLEC4G	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
DNAJC30	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
MGST1	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
SIGLEC12	TMPRSS4	psi-mi:“MI:0915”(physical association)	0.560
IL1RL1	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
CDIPT	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
ADIPOQ	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
ATP5PF	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
PTCH1	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
ACSF2	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
SIGLEC12	YIPF1	psi-mi:“MI:0915”(physical association)	0.560
SIGLEC12	HSPA5	psi-mi:“MI:0914”(association)	0.530
MIA3	CRTAP	psi-mi:“MI:0914”(association)	0.350
PPP4R3A	GRK6	psi-mi:“MI:0914”(association)	0.350
CLEC4G	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.000
DNAJC30	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.000
SIGLEC12	MGST1	psi-mi:“MI:0915”(physical association)	0.000
TMPRSS4	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.000
IL1RL1	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.000
CDIPT	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): SIGLEC12 (Affinity Capture-MS), SIGLEC12 (Affinity Capture-MS), TEX261 (Affinity Capture-MS), PLAA (Affinity Capture-MS), SLC39A11 (Affinity Capture-MS), TUBGCP3 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), UFSP2 (Affinity Capture-MS), MTX1 (Affinity Capture-MS), SIGLEC12 (Two-hybrid), SIGLEC12 (Two-hybrid), SIGLEC12 (Two-hybrid), SIGLEC12 (Two-hybrid), SIGLEC12 (Two-hybrid), SIGLEC12 (Two-hybrid)

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	143
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2139 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51265883:G:GG	donor_gain	1.0000
19:51267371:A:AG	acceptor_gain	1.0000
19:51267372:G:GG	acceptor_gain	1.0000
19:51268551:ATTTT:A	acceptor_gain	1.0000
19:51268555:T:TA	acceptor_gain	1.0000
19:51268558:A:AG	acceptor_gain	1.0000
19:51268558:ACCTC:A	acceptor_gain	1.0000
19:51268559:C:G	acceptor_gain	1.0000
19:51499164:TCTTA:T	donor_loss	1.0000
19:51499165:CTTAC:C	donor_loss	1.0000
19:51499166:TTA:T	donor_loss	1.0000
19:51499167:TACCT:T	donor_loss	1.0000
19:51499168:ACCTG:A	donor_loss	1.0000
19:51499169:CCTG:C	donor_loss	1.0000
19:51499214:GGAT:G	acceptor_gain	1.0000
19:51499215:GAT:G	acceptor_gain	1.0000
19:51499215:GATC:G	acceptor_loss	1.0000
19:51499217:TC:T	acceptor_loss	1.0000
19:51499218:C:CC	acceptor_gain	1.0000
19:51257845:G:T	donor_gain	0.9900
19:51257895:GCT:G	donor_gain	0.9900
19:51265580:GGCA:G	donor_gain	0.9900
19:51265603:G:GT	donor_gain	0.9900
19:51265603:G:T	donor_gain	0.9900
19:51265646:TC:T	donor_gain	0.9900
19:51265880:CATG:C	donor_loss	0.9900
19:51265882:TGT:T	donor_loss	0.9900
19:51265883:G:GA	donor_loss	0.9900
19:51265884:TGAG:T	donor_loss	0.9900
19:51265885:GAGTA:G	donor_loss	0.9900

AlphaMissense

3838 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51500068:G:C	F220L	0.990
19:51500068:G:T	F220L	0.990
19:51500070:A:G	F220L	0.990
19:51500069:A:C	F220C	0.981
19:51500158:C:A	W190C	0.980
19:51500158:C:G	W190C	0.980
19:51500069:A:G	F220S	0.975
19:51499985:A:G	F248S	0.973
19:51500036:C:G	C231S	0.972
19:51500037:A:T	C231S	0.972
19:51500160:A:G	W190R	0.971
19:51500160:A:T	W190R	0.971
19:51499984:G:C	F248L	0.967
19:51499984:G:T	F248L	0.967
19:51499986:A:G	F248L	0.967
19:51499991:T:G	Y246S	0.963
19:51500216:C:G	C171S	0.963
19:51500217:A:T	C171S	0.963
19:51499992:A:G	Y246H	0.962
19:51499991:T:C	Y246C	0.961
19:51500215:G:C	C171W	0.958
19:51500024:A:G	I235T	0.957
19:51501455:G:C	F93L	0.957
19:51501455:G:T	F93L	0.957
19:51501457:A:G	F93L	0.957
19:51499985:A:C	F248C	0.956
19:51499992:A:C	Y246D	0.954
19:51500035:G:C	C231W	0.951
19:51500217:A:G	C171R	0.948
19:51500155:G:C	F191L	0.947

dbSNP variants (sampled 300 via entrez): RS1000022309 (19:51499615 G>A), RS1000159951 (19:51492717 T>G), RS1000461322 (19:51502703 C>T), RS1000622458 (19:51491334 A>C), RS1000632065 (19:51498536 C>T), RS1000758566 (19:51491063 G>A,C), RS1000760331 (19:51494084 C>G,T), RS1000921295 (19:51493949 C>T), RS1001060176 (19:51500942 C>G), RS1001126610 (19:51503281 A>G), RS1001355735 (19:51492781 T>A), RS1001356193 (19:51498096 C>T), RS1002035680 (19:51497106 C>T), RS1002353440 (19:51494148 C>T), RS1002367226 (19:51499318 C>T)

Disease associations

OMIM: gene MIM:606094 | 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
GCST010988_314	Adult body size	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cisplatin	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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