LY9

protein-coding

lymphocyte antigen 9, the group of Immunoglobulin like domain containing|CD molecules

Gene summary

LY9 belongs to the SLAM family of immunomodulatory receptors (see SLAMF1; MIM 603492) and interacts with the adaptor molecule SAP (SH2D1A; MIM 300490) (Graham et al., 2006 [PubMed 16365421]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_002348.4

Inheritance

—

ClinVar variants

U:99B:12

Top phenotype

LY9-related disorder

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr1:160,796,074-160,828,483

External References & Databases

Ensembl (ENSG00000122224)

Transcript & Mutation Effects

hg38 • Region Span ~32.4 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 LY9 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 100

not providedTotal: 4

LY9-related disorderTotal: 1

Multisystem inflammatory syndrome in childrenTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002348.4. 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		2
missense			96 clinvar	8 clinvar	1 clinvar	105
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	0	99	11	1	111

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002348.4	RefSeq	NP_002339.2	10	MANE Select
ENST00000263285.11	Ensembl	ENSP00000263285.5	10	MANE Select
NM_001033667.3	RefSeq	NP_001028839.1	3	Standard
NM_001261456.2	RefSeq	NP_001248385.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Biological Process

cell adhesion
positive regulation of interleukin-17 production
innate immune response
T-helper 17 cell lineage commitment

Molecular Function

molecular_function

Cellular Component

plasma membrane
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263285
Coding exons: 10
Length: 32188
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125735
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.217	368	356	1.03	0.0000183	4256
Missense (PolyPhen)		83	90.545	0.91667		1201
Synonymous	0.800	134	146	0.916	0.00000828	1331
Loss of Function	1.08	23	29.3	0.785	0.00000162	319

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0.000066	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. May participate in adhesion reactions between T lymphocytes and accessory cells by homophilic interaction. Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A (PubMed:22184727). Promotes recruitment of RORC to the IL-17 promoter (PubMed:22989874). May be involved in the maintenance of peripheral cell tolerance by serving as a negative regulator of the immune response. May disable autoantibody responses and inhibit IFN-gamma secretion by CD4(+) T-cells. May negatively regulate the size of thymic innate CD8(+) T-cells and the development of invariant natural killer T (iNKT) cells (By similarity). {ECO:0000250|UniProtKB:Q01965, ECO:0000269|PubMed:22184727, ECO:0000269|PubMed:22989874}.;

Intolerance Scores

LoFtool: 0.966
RVIS EVS: 0.11
RVIS percentile EVS: 62.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.633

Gene Damage Prediction

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