SIGLEC1

protein-coding

sialic acid binding Ig like lectin 1, the group of V-set domain containing|CD molecules|C2-set domain containing|Sialic acid binding Ig like lectins|I-set domain containing

Gene summary

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. [provided by RefSeq, Dec 2021]

Previous symbols:

MANE transcript

NM_023068.4

Inheritance

—

ClinVar variants

U:291B:65

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr20:3,686,970-3,712,600

External References & Databases

Ensembl (ENSG00000088827)

Transcript & Mutation Effects

hg38 • Region Span ~25.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SIGLEC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 308

not providedTotal: 35

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_023068.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	13 clinvar	5 clinvar	23
missense			279 clinvar	44 clinvar	1 clinvar	324
nonsense			1 clinvar		1 clinvar	2
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	291	57	8	356

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_023068.4	RefSeq	NP_075556.1	21	MANE Select
ENST00000344754.6	Ensembl	ENSP00000341141.4	21	MANE Select
NM_001367089.1	RefSeq	NP_001354018.1	20	Standard
ENST00000419548.4	Ensembl	ENSP00000395778.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Immune System
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Adaptive Immune System

Biological Process

endocytosis
inflammatory response
cell-matrix adhesion
cell-cell adhesion

Molecular Function

carbohydrate binding

Cellular Component

extracellular region
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000344754
Coding exons: 21
Length: 20159
Individuals with no LoFs: 122940
Homozygous LoFs: 26
Heterozygous LoFs: 2782
Defined: 125748
p: 0.0112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.277	1075	1.05e+3	1.02	0.0000673	10778
Missense (PolyPhen)		297	322.19	0.92183		3696
Synonymous	0.114	446	449	0.993	0.0000286	3823
Loss of Function	-0.0527	69	68.5	1.01	0.00000391	681

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0034	0.0034	notable
Latino/Admixed American	0.0085	0.0085	notable
Ashkenazi Jewish	0.0094	0.0092	notable
East Asian	0.0065	0.0064	notable
Finnish	0.0024	0.0024	notable
European (Non-Finnish)	0.015	0.015	notable
South Asian	0.015	0.014	notable
Other	0.014	0.014	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as an endocytic receptor mediating clathrin dependent endocytosis. Macrophage-restricted adhesion molecule that mediates sialic-acid dependent binding to lymphocytes, including granulocytes, monocytes, natural killer cells, B-cells and CD8 T-cells. Preferentially binds to alpha-2,3-linked sialic acid (By similarity). Binds to SPN/CD43 on T-cells (By similarity). May play a role in hemopoiesis. {ECO:0000250}.;

Recessive Scores

pRec: 0.208

Intolerance Scores

LoFtool: 0.916
RVIS EVS: -1.81
RVIS percentile EVS: 2.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.154

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium