SIGLEC1

Summary

SIGLEC1 (sialic acid binding Ig like lectin 1, HGNC:11127) is a protein-coding gene on chromosome 20p13, encoding Sialoadhesin (Q9BZZ2). Macrophage-restricted adhesion molecule that mediates sialic-acid dependent binding to lymphocytes, including granulocytes, monocytes, natural killer cells, B-cells and CD8 T-cells.

This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a lectin-like adhesion molecule that binds glycoconjugate ligands on cell surfaces in a sialic acid-dependent manner. It is a type I transmembrane protein expressed only by a subpopulation of macrophages and is involved in mediating cell-cell interactions. The protein plays an important role in multiple human diseases and bacterial and viral infections has been shown to enhance SARS-CoV-2 infection.

Source: NCBI Gene 6614 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 369 total
• MANE Select transcript: NM_023068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11127
Approved symbol	SIGLEC1
Name	sialic acid binding Ig like lectin 1
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	SIGLEC-1, CD169, FLJ00051, FLJ00055, FLJ00073, FLJ32150, dJ1009E24.1
Ensembl gene	ENSG00000088827
Ensembl biotype	protein_coding
OMIM	600751
Entrez	6614

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000344754, ENST00000419548, ENST00000707083, ENST00000869140, ENST00000869141, ENST00000869142, ENST00000951921

RefSeq mRNA: 2 — MANE Select: NM_023068 NM_001367089, NM_023068

CCDS: CCDS13060

Canonical transcript exons

ENST00000344754 — 22 exons

Exon	Start	End
ENSE00000562089	3689600	3689702
ENSE00000858807	3689155	3689227
ENSE00001162111	3689962	3690264
ENSE00001162116	3691340	3691600
ENSE00001162121	3691903	3692202
ENSE00001162125	3692521	3692772
ENSE00001162389	3692862	3693131
ENSE00001162394	3693447	3693698
ENSE00001162402	3694221	3694532
ENSE00001162413	3694663	3694923
ENSE00001162421	3696586	3696888
ENSE00001162428	3697085	3697342
ENSE00001162436	3697798	3698133
ENSE00001162444	3699202	3699459
ENSE00001162452	3701342	3701641
ENSE00001162459	3703197	3703451
ENSE00001162465	3703825	3704091
ENSE00001162470	3705744	3706040
ENSE00001162476	3706347	3706706
ENSE00001674278	3707080	3707237
ENSE00001687615	3686970	3688619
ENSE00003910800	3712470	3712600

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 86.96.

FANTOM5 (CAGE): breadth broad, TPM avg 9.2304 / max 498.4405, expressed in 367 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186164	8.2354	364
186165	0.9790	175
186162	0.0160	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	86.96	gold quality
right coronary artery	UBERON:0001625	86.73	gold quality
decidua	UBERON:0002450	86.72	gold quality
omental fat pad	UBERON:0010414	84.76	gold quality
mucosa of stomach	UBERON:0001199	84.74	gold quality
peritoneum	UBERON:0002358	84.68	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.20	gold quality
granulocyte	CL:0000094	83.86	gold quality
right adrenal gland	UBERON:0001233	83.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.24	gold quality
layer of synovial tissue	UBERON:0007616	83.04	gold quality
adipose tissue	UBERON:0001013	82.43	gold quality
lymph node	UBERON:0000029	81.95	gold quality
left adrenal gland	UBERON:0001234	81.36	gold quality
connective tissue	UBERON:0002384	81.30	gold quality
adrenal cortex	UBERON:0001235	81.12	gold quality
apex of heart	UBERON:0002098	81.09	gold quality
spleen	UBERON:0002106	80.86	gold quality
left adrenal gland cortex	UBERON:0035825	80.86	gold quality
upper lobe of left lung	UBERON:0008952	80.53	gold quality
synovial joint	UBERON:0002217	80.52	gold quality
monocyte	CL:0000576	80.32	gold quality
leukocyte	CL:0000738	80.31	gold quality
mononuclear cell	CL:0000842	80.21	gold quality
upper lobe of lung	UBERON:0008948	80.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.01	gold quality
lower esophagus	UBERON:0013473	79.92	gold quality
tendon of biceps brachii	UBERON:0008188	79.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.56	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	871.96
E-MTAB-6678	yes	711.79
E-ANND-3	yes	19.04

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PITX2

miRNA regulators (miRDB)

87 targeting SIGLEC1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4306	99.72	70.50	3630
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-6848-3P	99.64	66.49	885
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-516A-3P	99.46	67.96	1378

Literature-anchored findings (GeneRIF, showing 40)

• Inhibitory signals delivered from human rhinovirus HRV14-treated dendritic cells to cocultured T cells via sialoadhesin (Sn) are critical for induction of T-cell anergy. (PMID:16002716)
• Increased expression of Siglec-1 in circulating systemic sclerosis (SSc) monocytes and tissue macrophages suggests type I IFN-mediated activation of monocytes occurs in SSc, possibly through toll-like receptor (TLR) activation of interferon secretion. (PMID:17328080)
• Sialoadhesin is induced to high levels on CD14(+) cells early after HIV-1 infection in vivo. (PMID:17330143)
• SIGLEC1, used as a surrogate marker for type I interferon, is a potential biomarker to assess disease acitvity in systemic lupus erythematosus (SLE). SIGLEC1+ resident monocytes could act as antigen presenting cells in SLE. (PMID:18383365)
• Siglec-1 (sialic acid binding Ig-like lectin 1) expression in resident blood monocytes is a potential biomarker for monitoring disease activity, displaying type I IFN responses, and estimating levels of anti-dsDNA antibodies (PMID:18383365)
• Increased sialoadhesin expression on CD14(+) monocytes occurs in response to HIV-1 infection with maximum expression associated with high viral load (PMID:18414664)
• Siglec-1 may be considered as a potential non-invasive indicator for monitoring disease severity and a biomarker for predicting the relative risk of cardiovascular events. (PMID:19285973)
• Data show that the combinatorial signal delivered by R-DC to T cells via B7-H1 and sialoadhesin is crucial for the induction of IL-35(+) Treg. (PMID:19950173)
• Increased expression in monocytes of patients with primary biliary cirrhosis (PMID:20653431)
• Monocytes overexpress sialoadhesin nonspecifically during intestinal transplant rejection and systemic or enteritic inflammatory states. (PMID:22249367)
• Based on increased SIGLEC1 expression in circulating monocytes, findings suggest a role for SIGLEC1 in the chronic progressive phases of multiple sclerosis. (PMID:22933622)
• These findings identify Siglec-1 as a key factor for HIV-1 spread via infectious dendritic/T-cell synapses. (PMID:23271952)
• downregulation of CD169 expression or neutralizing CD169 function abrogated dendritic cell-mediated HIV-1 capture and trans infection, while exogenous expression of CD169 in receptor-naive cells rescued glycosphingolipid-dependent capture and trans infection. (PMID:23593001)
• the CD169/Sn endocytic pathway is conserved and capable of presenting lipid antigens to iNKT cells (PMID:23610394)
• CD169(+) macrophages in RLNs promote CD8(+) T-cell-mediated antitumor immunity. (PMID:23734742)
• Siglec-1 may play a proinflammatory role in stimulating lymphocyte proliferation and activation in rheumatoid arthritis. (PMID:24196391)
• GM3-CD169 binding is a gp120-independent signal for sequestration and preservation of HIV-1 infectivity. (PMID:24947940)
• evidence identifying sialyllactose-containing gangliosides in the viral membrane and the cellular lectin Siglec-1 as critical determinants for HIV-1 capture and storage by mature DCs and for DC-mediated trans-infection of T cells (PMID:25033082)
• The most abundant cytokine present in semen (TGF-beta1) is able to enhance specifically the expression of an important molecule (CD169) involved in the capture and transmission of HIV-1 particles from the mucosal lumen to the submucosal compartment. (PMID:25354152)
• Our study suggests that HIV-1 capture by CD169 can provide virus evasion from both innate (phagocytosis) and adaptive immune responses (PMID:25760631)
• Siglec-1 on myeloid cells could fuel novel CD4(+) T-cell infections and contribute to HIV-1 dissemination in vivo. (PMID:25947229)
• These results highlight the importance of sialic acids on the V1V2 region in binding to sialic acid-binding immunoglobulin-like lectin. (PMID:26667473)
• Siglec-1 and Siglec-2 are potential biomarkers in autoimmune disease. (Review) (PMID:26752092)
• CD169 might act as a co-stimulatory molecule for cytotoxic T-cell activation, and could define a population of tumour-infiltrating macrophages with potential anti-tumour properties in human hepatocellular carcinoma tissues. (PMID:27174787)
• classical HIV-1 infectious routes may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within infected individuals (PMID:27510803)
• the antibody-sialidase conjugate desialylated tumor cells in a HER2-dependent manner, reduced binding by natural killer (NK) cell inhibitory sialic acid-binding Ig-like lectin (Siglec) receptors, and enhanced binding to the NK-activating receptor natural killer group 2D (NKG2D). (PMID:27551071)
• The results reveal marked differences between afferent and efferent ymphatic endothelial cells and identify molecules on lymphatic vessels. Further characterizations of Siglec-1 (CD169) and macrophage scavenger receptor 1 (MSR1/CD204), show that they are discriminatively expressed on lymphatic endothelium of the subcapsular sinus but not on lymphatic vasculature of the lymphatic sinus (PMID:27601677)
• These findings suggest that CD169+ macrophages in RLNs might be a useful marker for assessing clinical stage, including LN states, in patients with breast cancer. (PMID:27861544)
• this study shows that binding of monoclonal antibodies to Sn results in delayed and reduced phagocytosis of fluorescent beads, and that no effect is observed on Fc-mediated phagocytosis or phagocytosis of bacteria by macrophages (PMID:27993350)
• In colorectal tumor, malignant melanoma, and endometrial tumor, it was shown that a high density of CD169-positive macrophages in the lymph node sinus was a predictive factor for better clinical prognosis. (PMID:28002629)
• These data demonstrate a prominent role for Siglec-1 in the internalization of HIV-1 to the virus-containing compartment in infected monocyte-derived macrophages (PMID:28129379)
• High expression of SIGLEC1 in pregnant women with autoantibodies against Ro/SS-A indicates an enhanced risk for autoimmune congenital heart block development. (PMID:28501799)
• High CD169 expression is associated with HIV-1. (PMID:28794041)
• CD169 expression in regional LNs was not associated with PSA-relapse. (PMID:28880401)
• Our findings evidenced for the first time the novel association between SIGLEC1 rs3859664 SNP and active pulmonary TB. Intriguingly, carriers of the polymorphism produced less IL-1ss than non-carriers, suggesting the possible involvement of Siglec-1 signalling pathway with inflammasome complex. (PMID:28964857)
• SIGLEC1 mRNA levels have potential as a novel predictive biomarker for Graves disease relapse. (PMID:29037117)
• In vitro, respiratory syncytial virus (RSV) increased expression of Siglec-1 on healthy newborn and adult monocytes. RSV-induced Siglec-1 on monocytes inhibited Interferon gamma production by adult CD4(+) T cells. In contrast,Interferon gamma production by RSV in newborns was not affected by Siglec-1. (PMID:29266251)
• suggest that high expression of CD169 in lymph node sinus macrophages reflects a high potential for anti-cancer immune responses in esophageal cancer patients (PMID:30516869)
• circulating dendritic cell precursors, but not other blood dendritic cell subsets, are susceptible to infection by HIV-1 in a Siglec-1-dependent manner. This constitutes a unique functional feature that might represent a preferential relationship of this emerging cell type with viruses. (PMID:31591213)
• Decreased expression of a phagocytic receptor Siglec-1 on alveolar macrophages in chronic obstructive pulmonary disease. (PMID:31992280)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Siglec1	ENSMUSG00000027322
rattus_norvegicus	Siglec1	ENSRNOG00000021243

Paralogs (16): CD22 (ENSG00000012124), 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), SIGLEC12 (ENSG00000254521), SIGLEC5 (ENSG00000268500)

Protein

Protein identifiers

Sialoadhesin — Q9BZZ2 (reviewed: Q9BZZ2)

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

All UniProt accessions (2): Q9BZZ2, H7C0M6

UniProt curated annotations — full annotation on UniProt →

Function. Macrophage-restricted adhesion molecule that mediates sialic-acid dependent binding to lymphocytes, including granulocytes, monocytes, natural killer cells, B-cells and CD8 T-cells. Plays a crucial role in limiting bacterial dissemination by engaging sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response. Mediates the uptake of various enveloped viruses via sialic acid recognition and subsequently induces the formation of intracellular compartments filled with virions (VCCs). In turn, enhances macrophage-to-T-cell transmission of several viruses including HIV-1 or SARS-CoV-2. Acts as an endocytic receptor mediating clathrin dependent endocytosis. Preferentially binds to alpha-2,3-linked sialic acid. Binds to SPN/CD43 on T-cells. May play a role in hemopoiesis. Plays a role in the inhibition of antiviral innate immune by promoting TBK1 degradation via TYROBP and TRIM27-mediated ubiquitination. (Microbial infection) Facilitates viral cytoplasmic entry into activated dendritic cells via recognition of sialylated gangliosides pesent on viral membrane.

Subunit / interactions. Interacts with TYROBP. Interacts with CLEC10A.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expressed by macrophages in various tissues. High levels are found in spleen, lymph node, perivascular macrophages in brain and lower levels in bone marrow, liver Kupffer cells and lamina propria of colon and lung. Also expressed by inflammatory macrophages in rheumatoid arthritis.

Induction. By interferon-alpha. By viral infection.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BZZ2-1	1	yes
Q9BZZ2-2	2
Q9BZZ2-3	3

RefSeq proteins (2): NP_001354018, NP_075556* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07679, PF07686, PF08205, PF13895

UniProt features (71 total): disulfide bond 18, domain 17, glycosylation site 14, sequence variant 9, binding site 3, topological domain 2, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZZ2-F1	77.26	0.07

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 (3): 63; 116; 122–126

Disulfide bonds (18): 36–166, 41–98, 160–217, 262–305, 346–390, 433–491, 531–575, 624–689, 729–774, 817–876, 916–960, 1005–1067, 1107–1149, 1193–1241, 1281–1324, 1367–1425, 1465–1511, 1554–1613

Glycosylation sites (14): 159, 265, 339, 499, 697, 726, 730, 741, 886, 1104, 1138, 1251, 1462, 1476

Mutagenesis-validated functional residues (1):

Position	Phenotype
116	complete loss of sialic acid recognition capacity.

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: 163 (showing top): TSENG_IRS1_TARGETS_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_CYTOKINE_PRODUCTION, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_HOST, GOBP_VIRAL_LIFE_CYCLE, DODD_NASOPHARYNGEAL_CARCINOMA_UP, SABATES_COLORECTAL_ADENOMA_DN, GOBP_CELL_SUBSTRATE_ADHESION, GOBP_IMPORT_INTO_CELL

GO Biological Process (8): inflammatory response (GO:0006954), cell-matrix adhesion (GO:0007160), negative regulation of type I interferon production (GO:0032480), clathrin-dependent endocytosis of virus by host cell (GO:0075512), cell-cell adhesion (GO:0098609), endocytosis (GO:0006897), cell adhesion (GO:0007155), positive regulation of type I interferon production (GO:0032481)

GO Molecular Function (2): carbohydrate binding (GO:0030246), virion binding (GO:0046790)

GO Cellular Component (5): extracellular region (GO:0005576), early endosome (GO:0005769), late endosome (GO:0005770), 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
regulation of type I interferon production	2
type I interferon production	2
cellular anatomical structure	2
endosome	2
defense response	1
cell-substrate adhesion	1
negative regulation of cytokine production	1
receptor-mediated endocytosis of virus by host cell	1
symbiont entry into host cell	1
clathrin-dependent endocytosis	1
cell adhesion	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cellular process	1
positive regulation of cytokine production	1
binding	1
protein binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIGLEC1	MUC1	P13931	982
SIGLEC1	GP5	P40197	947
SIGLEC1	SPN	P16150	899
SIGLEC1	TRIM27	P14373	805
SIGLEC1	CD163	Q86VB7	798
SIGLEC1	SELPLG	Q14242	794
SIGLEC1	CD68	P34810	764
SIGLEC1	ITGAM	P11215	754
SIGLEC1	SIGLEC15	Q6ZMC9	736
SIGLEC1	CD209	Q9NNX6	732
SIGLEC1	IFI44L	Q53G44	728
SIGLEC1	TYROBP	O43914	672
SIGLEC1	ITGAX	P20702	665
SIGLEC1	MX1	P20591	638
SIGLEC1	CD151	P48509	623

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SIGLEC1	SPN	psi-mi:“MI:0407”(direct interaction)	0.440
SIGLEC1	CD33	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	SIGLEC1	psi-mi:“MI:0915”(physical association)	0.400
MXRA5	SIGLEC1	psi-mi:“MI:0915”(physical association)	0.400
SIGLEC5	SIGLEC1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): SIGLEC1 (Affinity Capture-MS), S (Reconstituted Complex), SIGLEC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O14498, O15197, O70394, O70540, P01877, P0C0K6, P0C788, P0DP72, P35590, P40223, P43121, P50895, P70289, Q00657, Q06418, Q06805, Q15109, Q28173, Q5BK54, Q5NVQ6, Q5TJE4, Q61790, Q61826, Q62151, Q62230, Q63495, Q64612, Q6UVK1, Q6UWB1, Q7Z442, Q86VR7, Q8IZF5, Q8R2Y2, Q8VHY0

Diamond homologs: A7LCJ3, Q62230, Q8WZ75, Q9BZZ2, Q9N1E3, Q9Z109, A0A0B4J1L0, A0A140LHF2, D3ZQE1, E9QA28, O75871, P06731, P11464, P11465, P13688, P16573, P20273, P31809, P31997, P35329, P40198, P40199, Q00887, Q00888, Q00889, Q13046, Q14002, Q15238, Q16557, Q2WEN9, Q3KPI0, Q3UKK2, Q61400, Q63111, Q810J1, Q925P2, Q92626, Q9D2Z1, Q9D871, Q9N1E4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	270
Likely benign	52
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

3931 predictions. Top by Δscore:

Variant	Effect	Δscore
20:3690261:GGGT:G	acceptor_gain	1.0000
20:3690262:GGT:G	acceptor_gain	1.0000
20:3690263:GT:G	acceptor_gain	1.0000
20:3690265:C:CC	acceptor_gain	1.0000
20:3690266:T:G	acceptor_loss	1.0000
20:3691338:A:AC	donor_gain	1.0000
20:3691339:C:CC	donor_gain	1.0000
20:3692643:T:TA	donor_gain	1.0000
20:3692860:AC:A	donor_gain	1.0000
20:3692861:CC:C	donor_gain	1.0000
20:3693528:C:A	donor_gain	1.0000
20:3694217:TGAC:T	donor_loss	1.0000
20:3694218:GACC:G	donor_loss	1.0000
20:3694220:CCT:C	donor_loss	1.0000
20:3696581:CTCA:C	donor_loss	1.0000
20:3696584:ACC:A	donor_loss	1.0000
20:3697794:TCAC:T	donor_loss	1.0000
20:3697796:A:AC	donor_gain	1.0000
20:3697796:A:T	donor_loss	1.0000
20:3697796:AC:A	donor_gain	1.0000
20:3697797:C:CC	donor_gain	1.0000
20:3697797:C:CT	donor_loss	1.0000
20:3697797:CC:C	donor_gain	1.0000
20:3701336:TCTTA:T	donor_loss	1.0000
20:3701337:CTTAC:C	donor_loss	1.0000
20:3701338:TTACC:T	donor_loss	1.0000
20:3701339:TACC:T	donor_loss	1.0000
20:3701340:A:AC	donor_gain	1.0000
20:3701340:A:AT	donor_loss	1.0000
20:3701341:C:A	donor_loss	1.0000

AlphaMissense

10912 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:3705925:C:A	W175C	0.996
20:3705925:C:G	W175C	0.996
20:3696806:G:C	S821R	0.992
20:3696806:G:T	S821R	0.992
20:3696808:T:G	S821R	0.992
20:3696629:A:C	N880K	0.991
20:3696629:A:T	N880K	0.991
20:3698036:G:C	S628R	0.991
20:3698036:G:T	S628R	0.991
20:3698038:T:G	S628R	0.991
20:3699271:A:C	Y573D	0.989
20:3701559:A:C	S437R	0.989
20:3701559:A:T	S437R	0.989
20:3701561:T:G	S437R	0.989
20:3706693:C:A	W21C	0.989
20:3706693:C:G	W21C	0.989
20:3692120:A:C	S1371R	0.988
20:3692120:A:T	S1371R	0.988
20:3692122:T:G	S1371R	0.988
20:3706409:C:G	R116P	0.988
20:3705927:A:G	W175R	0.987
20:3705927:A:T	W175R	0.987
20:3706579:C:A	W59C	0.987
20:3706579:C:G	W59C	0.987
20:3706381:C:A	W125C	0.986
20:3706381:C:G	W125C	0.986
20:3706405:G:C	F117L	0.986
20:3706405:G:T	F117L	0.986
20:3706407:A:G	F117L	0.986
20:3706581:A:G	W59R	0.986

dbSNP variants (sampled 300 via entrez): RS1000055489 (20:3709742 A>G), RS1000133926 (20:3688809 T>C), RS1000516888 (20:3695769 G>A,C), RS1000583117 (20:3700475 T>C,G), RS1000743227 (20:3712160 G>A,T), RS1001053723 (20:3700663 A>G), RS1001071186 (20:3689573 C>G,T), RS1001197054 (20:3708626 G>A,T), RS1001283279 (20:3714199 C>T), RS1001326672 (20:3713517 GCCCCCA>G), RS1001722123 (20:3703508 C>T), RS1001791006 (20:3697404 C>T), RS1001834646 (20:3708340 C>T), RS1001955542 (20:3697670 T>C), RS1002224562 (20:3696412 G>C)

Disease associations

OMIM: gene MIM:600751 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003542_159	Night sleep phenotypes	8.000000e-06
GCST008473_52	Visceral fat	6.000000e-06
GCST008575_5	IgM levels	3.000000e-15
GCST90002406_541	Reticulocyte fraction of red cells	1.000000e-12
GCST90013407_187	Liver enzyme levels (gamma-glutamyl transferase)	1.000000e-41

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Asian ginseng	affects cotreatment, decreases expression	1
methyleugenol	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
theaflavin-3,3’-digallate	affects expression	1
Irinotecan	affects cotreatment, increases expression	1
Allergens	decreases expression	1
Amphotericin B	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	increases expression	1
Diethylhexyl Phthalate	decreases expression, affects cotreatment	1
Fluorouracil	affects cotreatment, increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Nickel	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Zidovudine	affects cotreatment, increases expression	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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