SIGLEC8

protein-coding

sialic acid binding Ig like lectin 8, the group of V-set domain containing|Sialic acid binding Ig like lectins

Gene summary

Sialic acid-binding immunoglobulin (Ig)-like lectins, or SIGLECs (e.g., CD33 (MIM 159590)), are a family of type 1 transmembrane proteins each having a unique expression pattern, mostly in hemopoietic cells. SIGLEC8 is a member of the CD33-like subgroup of SIGLECs, which are localized to 19q13.3-q13.4 and have 2 conserved cytoplasmic tyrosine-based motifs: an immunoreceptor tyrosine-based inhibitory motif, or ITIM (see MIM 604964), and a motif homologous to one identified in signaling lymphocyte activation molecule (SLAM; MIM 603492) that mediates an association with SLAM-associated protein (SAP; MIM 300490) (summarized by Foussias et al., 2000 [PubMed 11095983]).[supplied by OMIM, May 2010]

MANE transcript

NM_014442.3

Inheritance

—

ClinVar variants

U:81B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr19:51,450,847-51,458,456

External References & Databases

Ensembl (ENSG00000105366)

Transcript & Mutation Effects

hg38 • Region Span ~7.6 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 SIGLEC8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014442.3. 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	2
missense			79 clinvar	4 clinvar	1 clinvar	84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	81	4	3	88

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014442.3	RefSeq	NP_055257.2	7	MANE Select
ENST00000321424.7	Ensembl	ENSP00000321077.2	7	MANE Select
NM_001363548.1	RefSeq	NP_001350477.1	6	Standard
ENST00000340550.5	Ensembl	ENSP00000339448.4	6	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
signal transduction

Molecular Function

transmembrane signaling receptor activity
protein binding
carbohydrate binding

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321424
Coding exons: 7
Length: 7610
Individuals with no LoFs: 125621
Homozygous LoFs: 0
Heterozygous LoFs: 125
Defined: 125746
p: 0.000497

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0824	274	278	0.986	0.0000151	3168
Missense (PolyPhen)		64	66.506	0.96232		840
Synonymous	0.479	116	123	0.945	0.00000703	1079
Loss of Function	1.37	13	19.5	0.665	0.00000104	200

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.0074	0.0075	notable
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00023	0.00023	rare
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative adhesion molecule that mediates sialic-acid dependent binding to red blood cells (PubMed:10856141, PubMed:10625619). Preferentially binds to alpha-2,3-linked sialic acid. Also binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface (PubMed:10625619). Recognizes simultaneously epitopes having a terminal N-acetylneuraminic acid (sialic acid) and an underlying 6-O-sulfated galactose. Preferentially binds to Gal-6-sulfated sialyl-Lewis X glycan epitopes (PubMed:27357658). {ECO:0000269|PubMed:10625619, ECO:0000269|PubMed:10856141, ECO:0000269|PubMed:27357658}.;

Intolerance Scores

LoFtool: 0.825
RVIS EVS: 0.6
RVIS percentile EVS: 82.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0733

Gene Damage Prediction

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