SIGLEC10

protein-coding

sialic acid binding Ig like lectin 10, the group of V-set domain containing|C2-set domain containing|Sialic acid binding Ig like lectins

Gene summary

SIGLECs are members of the immunoglobulin superfamily that are expressed on the cell surface. Most SIGLECs have 1 or more cytoplasmic immune receptor tyrosine-based inhibitory motifs, or ITIMs. SIGLECs are typically expressed on cells of the innate immune system, with the exception of the B-cell expressed SIGLEC6 (MIM 604405).[supplied by OMIM, Jul 2002]

MANE transcript

NM_033130.5

Inheritance

—

ClinVar variants

U:103B:32

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr19:51,410,020-51,417,803

External References & Databases

Ensembl (ENSG00000142512)

Transcript & Mutation Effects

hg38 • Region Span ~7.8 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 SIGLEC10 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033130.5. 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			4 clinvar	6 clinvar	2 clinvar	12
missense			95 clinvar	23 clinvar	1 clinvar	119
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	103	29	3	135

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033130.5	RefSeq	NP_149121.2	11	MANE Select
ENST00000339313.10	Ensembl	ENSP00000345243.4	11	MANE Select
NM_001171156.2	RefSeq	NP_001164627.1	11	Standard
NM_001171157.2	RefSeq	NP_001164628.1	10	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

adaptive immune response
cell adhesion
innate immune response
negative regulation of inflammatory response to wounding

Molecular Function

protein binding
phosphatase binding
carbohydrate binding
SH2 domain binding

Cellular Component

extracellular region
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356298
Coding exons: 11
Length: 7783
Individuals with no LoFs: 125627
Homozygous LoFs: 0
Heterozygous LoFs: 121
Defined: 125748
p: 0.000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.00	350	407	0.860	0.0000244	4423
Missense (PolyPhen)		81	103.98	0.77903		1262
Synonymous	-0.378	185	179	1.04	0.0000115	1472
Loss of Function	3.23	15	35.9	0.418	0.00000214	350

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.0016	0.0016	notable
East Asian	0.000054	0.000054	rare
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.00067	0.00066	rare
South Asian	0.00039	0.00039	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. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid (By similarity). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, seems to act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules (PubMed:11284738, PubMed:12163025). Involved in negative regulation of B-cell antigen receptor signaling. The inhibition of B cell activation is dependent on PTPN6/SHP-1 (By similarity). In association with CD24 may be involved in the selective suppression of the immune response to danger-associated molecular patterns (DAMPs) such as HMGB1, HSP70 and HSP90 (By similarity). In association with CD24 may regulate the immune repsonse of natural killer (NK) cells (PubMed:25450598). Plays a role in the control of autoimmunity (By similarity). During initiation of adaptive immune responses by CD8-alpha(+) dendritic cells inhibits cross-presentation by impairing the formation of MHC class I-peptide complexes. The function seems to implicate recruitment of PTPN6/SHP-1, which dephosphorylates NCF1 of the NADPH oxidase complex consequently promoting phagosomal acidification (By similarity). {ECO:0000250|UniProtKB:Q80ZE3, ECO:0000269|PubMed:11284738, ECO:0000269|PubMed:25450598, ECO:0000305|PubMed:12163025}.;

Recessive Scores

pRec: 0.0813

Intolerance Scores

RVIS EVS: -0.24
RVIS percentile EVS: 36.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.353

Gene Damage Prediction

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