KIR2DL3

protein-coding

killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3, the group of CD molecules|Killer cell immunoglobulin like receptors

Gene summary

Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. [provided by RefSeq, Jul 2008]

MANE transcript

NM_015868.3

Inheritance

—

ClinVar variants

U:67B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.02

Max pathogenic AF

—

Genomic locus

chr19:54,738,513-54,753,052

External References & Databases

Ensembl (ENSG00000243772)

Transcript & Mutation Effects

hg38 • Region Span ~14.5 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 KIR2DL3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015868.3. 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				4 clinvar		4
missense			67 clinvar	7 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	67	11	0	78

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015868.3	RefSeq	NP_056952.2	8	MANE Select
ENST00000342376.4	Ensembl	ENSP00000342215.3	8	MANE Select
ENST00000880264.1	Ensembl	ENSP00000550323.1	9	Standard
ENST00000880264.2	Ensembl	ENSP00000550323.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antigen processing and presentation - Homo sapiens (human)
Graft-versus-host disease - Homo sapiens (human)
Natural killer cell mediated cytotoxicity - Homo sapiens (human)
Cellular senescence - Homo sapiens (human)
Immune System

Biological Process

immune response
regulation of immune response

Molecular Function

antigen binding
protein binding
signaling receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342376
Coding exons: 8
Length: 45797
Individuals with no LoFs: 120522
Homozygous LoFs: 12
Heterozygous LoFs: 59
Defined: 120593
p: 0.000294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.68	230	169	1.36	0.00000885	2169
Missense (PolyPhen)		85	71.078	1.1959		996
Synonymous	-3.52	104	67.3	1.55	0.00000401	664
Loss of Function	-0.0819	13	12.7	1.02	5.37e-7	175

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.00097	notable
Latino/Admixed American	0.00062	0.00051	rare
Ashkenazi Jewish	0.0022	0.0016	notable
East Asian	0.00033	0.00028	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00012	rare
South Asian	0.000081	0.000069	rare
Other	0.00073	0.00069	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor on natural killer (NK) cells for HLA-C alleles (HLA-Cw1, HLA-Cw3 and HLA-Cw7). Inhibits the activity of NK cells thus preventing cell lysis.;

Intolerance Scores

LoFtool: 0.962
RVIS EVS: 2.55
RVIS percentile EVS: 98.73

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.355

Gene Damage Prediction

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