KIR2DL1
protein-codingkiller cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 1, 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
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.5 kbGenCC 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 KIR2DL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014218.3. 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 | 3 | 3 | ||||
| missense | 5 | 5 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 1 | 8 | 0 | 9 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055033.2 | 8 | MANE Select | |
| Ensembl | ENSP00000336769.5 | 8 | MANE Select | |
| Ensembl | ENSP00000291633.7 | 9 | Standard | |
| Ensembl | ENSP00000291633.7 | 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
- natural killer cell inhibitory signaling pathway
- immune response
- regulation of immune response
Molecular Function
- protein binding
- signaling receptor activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000336077
- Coding exons
- 8
- Length
- 14512
- Individuals with no LoFs
- 122628
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 19
- Defined
- 122649
- p
- 0.0000856
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -2.10 | 262 | 182 | 1.44 | 0.0000101 | 2199 |
| Missense (PolyPhen) | 98 | 73.611 | 1.3313 | 1024 | ||
| Synonymous | -3.20 | 108 | 73.1 | 1.48 | 0.00000449 | 684 |
| Loss of Function | -1.34 | 19 | 13.7 | 1.39 | 6.42e-7 | 176 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00020 | 0.00019 | rare |
| Latino/Admixed American | 0.000061 | 0.000060 | rare |
| Ashkenazi Jewish | 0.00011 | 0.00011 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000075 | 0.000072 | rare |
| South Asian | 0.00026 | 0.00017 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor on natural killer (NK) cells for some HLA-C alleles such as w4 and w6. Inhibits the activity of NK cells thus preventing cell lysis. {ECO:0000269|PubMed:18604210}.;
Intolerance Scores
- LoFtool
- 0.974
- RVIS EVS
- 1.15
- RVIS percentile EVS
- 92.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.509
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |