SIGLEC8

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

Basic information

Region (hg38): 19:51450846-51458456

Links

ENSG00000105366 ∙ NCBI:27181 ∙ OMIM:605639 ∙ HGNC:10877 ∙ Uniprot:Q9NYZ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SIGLEC8 gene.

• Inborn genetic diseases (20 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SIGLEC8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			18	2	1	21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	2	3

Variants in SIGLEC8

This is a list of pathogenic ClinVar variants found in the SIGLEC8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-51452446-C-T		not specified	Uncertain significance (May 30, 2023)
19-51452488-T-G		not specified	Uncertain significance (Jun 02, 2023)
19-51452558-C-T		not specified	Uncertain significance (Dec 04, 2023)
19-51452586-A-C			Benign (Jul 13, 2018)
19-51454242-C-T		not specified	Uncertain significance (Dec 09, 2023)
19-51454733-C-T		not specified	Uncertain significance (Dec 11, 2023)
19-51455420-G-A		not specified	Uncertain significance (Aug 13, 2021)
19-51455477-T-C		not specified	Uncertain significance (Dec 08, 2023)
19-51455489-G-A		not specified	Uncertain significance (Aug 30, 2022)
19-51455511-C-T		not specified	Uncertain significance (Feb 06, 2023)
19-51455579-C-G		not specified	Uncertain significance (Sep 27, 2022)
19-51455603-G-T		not specified	Uncertain significance (Dec 28, 2023)
19-51455604-G-A		not specified	Uncertain significance (Dec 22, 2023)
19-51455613-T-C		not specified	Likely benign (May 23, 2023)
19-51455668-A-T		not specified	Uncertain significance (Mar 27, 2023)
19-51457463-G-A			Benign (Jul 13, 2018)
19-51457479-C-T		not specified	Likely benign (Jul 09, 2021)
19-51457491-T-C		not specified	Uncertain significance (May 03, 2023)
19-51457568-A-G		not specified	Uncertain significance (Dec 17, 2023)
19-51457581-G-A		not specified	Uncertain significance (Apr 28, 2022)
19-51457619-A-G		not specified	Uncertain significance (Nov 05, 2021)
19-51457623-A-G		not specified	Uncertain significance (Jun 11, 2021)
19-51457655-G-T		not specified	Uncertain significance (Oct 13, 2023)
19-51457969-T-C		not specified	Uncertain significance (Apr 25, 2022)
19-51458003-C-G		not specified	Uncertain significance (Aug 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SIGLEC8	protein_coding	protein_coding	ENST00000321424	7	7610

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.22e-7	0.787	125621	0	125	125746	0.000497

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0824	274	278	0.986	0.0000151	3168
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000825	0.000825
Ashkenazi Jewish	0.00744	0.00747
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000203	0.000202
Middle Eastern	0.0000544	0.0000544
South Asian	0.000230	0.000229
Other	0.000655	0.000652

dbNSFP

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}.
• Pathway: Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System (Consensus)

Intolerance Scores

• loftool: 0.825
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.83

Haploinsufficiency Scores

• pHI: 0.208
• hipred: N
• hipred_score: 0.158
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0733

Gene Damage Prediction

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

Gene ontology

• Biological process: cell adhesion;signal transduction
• Cellular component: integral component of membrane
• Molecular function: transmembrane signaling receptor activity;protein binding;carbohydrate binding