SIGLEC12

protein-coding

sialic acid binding Ig like lectin 12, the group of V-set domain containing|C2-set domain containing|Sialic acid binding Ig like lectins|I-set domain containing

Gene summary

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. [provided by RefSeq, Aug 2013]

Previous symbols:

SIGLECL1

MANE transcript

NM_053003.4

Inheritance

—

ClinVar variants

U:124B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr19:51,491,227-51,501,800

External References & Databases

Ensembl (ENSG00000254521)

Transcript & Mutation Effects

hg38 • Region Span ~10.6 kb

Loading mutation effect viewer...

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 SIGLEC12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 124

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_053003.4. 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			2 clinvar	1 clinvar	2 clinvar	5
missense			122 clinvar	3 clinvar		125
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	124	4	2	130

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_053003.4	RefSeq	NP_443729.1	8	MANE Select
ENST00000291707.8	Ensembl	ENSP00000291707.3	8	MANE Select
NM_033329.2	RefSeq	NP_201586.1	7	Standard
ENST00000596742.1	Ensembl	ENSP00000469791.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Immune System
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Adaptive Immune System

Biological Process

cell adhesion

Molecular Function

carbohydrate binding

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291707
Coding exons: 8
Length: 10433
Individuals with no LoFs: 125673
Homozygous LoFs: 0
Heterozygous LoFs: 75
Defined: 125748
p: 0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.673	363	329	1.10	0.0000173	3801
Missense (PolyPhen)		95	96.129	0.98826		1211
Synonymous	-2.05	177	146	1.22	0.00000851	1253
Loss of Function	0.661	22	25.6	0.859	0.00000154	247

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.00028	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.00024	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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.;

Intolerance Scores

LoFtool: 0.945
RVIS EVS: 2.34
RVIS percentile EVS: 98.4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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