KIR2DL5A

Summary

KIR2DL5A (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 5A, HGNC:16345) is a protein-coding gene on chromosome 19q13.4 alternate reference locus, encoding Killer cell immunoglobulin-like receptor 2DL5A (Q8N109). Receptor on natural killer (NK) cells for HLA-C alleles.

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.

Source: NCBI Gene 57292 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_020535

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16345
Approved symbol	KIR2DL5A
Name	killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 5A
Location	19q13.4 alternate reference locus
Locus type	gene with protein product
Status	Approved
Aliases	KIR2DL5.1, KIR2DL5, CD158F
Ensembl gene	ENSG00000274143
OMIM	605305
Entrez	57292

Gene structure

Transcript identifiers

Ensembl transcripts: 0

RefSeq mRNA: 1 — MANE Select: NM_020535 NM_020535

Canonical transcript exons

ENST00000611422 — 0 exons

Expression profiles

Top tissues by expression

0 total, by Bgee expression score (0-100, higher = more expressed):

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 21)

• Human KIR2DL5 has at least 4 gene variants, whose exons differ by 2 to 8 nucleotides. These structurally similar variants are encoded by alleles of 2 different loci, KIR2DL5A and KIR2DL5B, which map to different regions of the KIR-gene cluster. (PMID:12185535)
• The frequencies of KIR2DS1 and KIR2DL5 were significantly increased in psoriasis vulgaris cases compared with controls (PMID:15140215)
• the cytoplasmic domains of type II KIRs (2DL4 and 2DL5) exhibit distinct inhibitory capacities when compared with type I KIRs (3DL1), due to alterations in the canonical immunoreceptor tyrosine-based inhibitory motifs (PMID:15187115)
• We report here the identification and characterization of the receptor encoded by KIR2DL5 using a newly generated specific mAb that recognizes its most commonly expressed allele, KIR2DL5A*001. (PMID:17371997)
• Sequencing a KIR2DL5 variant using a first-generation high-throughput method proves it is a newly discovered allele, one that appears associated with Hispanic and Native American populations. (PMID:17464504)
• we investigate the relationship between the sequence diversity of KIR2DL5, including three novel alleles, and its variable transcription. (PMID:17557377)
• Carriage of inhibitory 2dl5 was increased in patients with herpes virus RDs. (PMID:17592337)
• Promoter variants of KIR2DL5 add to diversity and may impact gene expression. (PMID:18461314)
• Alleles commonly found in a Northern Irish population of 354 individuals were KIR2DL5A*001, KIR2DL5A*005, and KIR2DL5B*002. (PMID:18498296)
• The nature of KIR2DL5 gene polymorphism into four ethnic groups using direct DNA sequencing method was elucidated. (PMID:18509341)
• KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy. (PMID:20456039)
• indicate that killer-cell immunoglobulin-like receptors (KIRs)activator (KIR3DS1 and KIR2DS5) and inhibitory (KIR2DL5) genes are associated with severe pandemic influenza A (H1N1) 2009 infections. (PMID:22652695)
• A significant upregulation of KIR2DL5A occurs in Alzheimer’s disease fast progessors compared to slow progressors. (PMID:23234877)
• The genes KIR2DL5, KIR2DS3 and KIR2DS5 were present in a significantly higher proportion of individuals in the asymptomatic control group than in the malaria cases. (PMID:24929143)
• Data show that KIR2DL5 receptor, KIR2DS1 protein, KIR2DS5 protein and KIR3DS1 receptors were all significantly associated with high viral load. (PMID:25253288)
• KIR2DL5 gene polymorphism is associated with HIV-1 infection. (PMID:26888639)
• We observed statistically lower carrier frequencies of cB03|tA01 gene-content haplotype, of cB03 haplotype motif, of the KIR2DL5 + 2DS3/2DS5 gene pair and of KIR2DL5 amongst CMV-positive pregnant women in comparison with those CMV negative (PMID:27277336)
• Loss of KIR2DL5A gene is associated with breast cancer. (PMID:27631728)
• these findings establish KIR2DL5 as a new Schwann cell growth regulator relevant to sp-DNF pathogenesis, which links sporadic and NF1-associated DNFs through RAS pathway hyperactivation. (PMID:28548933)
• KIR 2DL5 was associated with decreased CMV infection and better platelets engraftment after hematopoietic stem cell transplantation from matched sibling (PMID:28993188)
• Association of KIR2DL5, KIR2DS5, and KIR2DS1 allelic variation and atopic dermatitis. (PMID:36720995)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Killer cell immunoglobulin-like receptor 2DL5A — Q8N109 (reviewed: Q8N109)

All UniProt accessions (2): A0A191URI1, Q8N109

UniProt curated annotations — full annotation on UniProt →

Function. Receptor on natural killer (NK) cells for HLA-C alleles. Inhibits the activity of NK cells thus preventing cell lysis.

Subcellular location. Cell membrane.

Similarity. Belongs to the immunoglobulin superfamily.

RefSeq proteins (1): NP_065396* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050412	Ig-like_Receptors_ImmuneReg	Family

Pfam: PF00047

UniProt features (16 total): glycosylation site 3, compositionally biased region 2, disulfide bond 2, topological domain 2, domain 2, region of interest 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N109-F1	71.56	0.44

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 49–95, 144–193

Glycosylation sites (3): 139, 173, 218

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): GOBP_REGULATION_OF_IMMUNE_RESPONSE, KEGG_GRAFT_VERSUS_HOST_DISEASE, KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION, PARENT_MTOR_SIGNALING_UP, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_IMMUNE_RESPONSE_INHIBITING_SIGNAL_TRANSDUCTION, IL2_UP.V1_UP, IL21_UP.V1_UP, KRAS.DF.V1_DN, GOMF_IMMUNE_RECEPTOR_ACTIVITY, GSE12845_NAIVE_VS_PRE_GC_TONSIL_BCELL_UP, PUIFFE_INVASION_INHIBITED_BY_ASCITES_UP, KAZMIN_PBMC_P_FALCIPARUM_RTSS_AS01_AGE_UNKNOWN_CORRELATED_WITH_PROTECTION_56DY_NEGATIVE, NAKAYA_PLASMACYTOID_DENDRITIC_CELL_FLUMIST_AGE_18_50YO_7DY_DN

GO Biological Process (1): immune response-regulating signaling pathway (GO:0002764)

GO Molecular Function (0):

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	1
regulation of immune response	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

12 interactions, top by confidence:

A	B	Type	Score
PVR	KIR2DL5A	psi-mi:“MI:0915”(physical association)	0.750
PVR	KIR2DL5A	psi-mi:“MI:0407”(direct interaction)	0.750
KIR2DL5A	PVR	psi-mi:“MI:0915”(physical association)	0.750
KIR2DL5A	PVR	psi-mi:“MI:0403”(colocalization)	0.750
KIR2DL5A	PVR	psi-mi:“MI:0407”(direct interaction)	0.750
KIR2DL5A	MPZ	psi-mi:“MI:0915”(physical association)	0.400
KIR2DL5A	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.400
KIR2DL5A	AXL	psi-mi:“MI:0915”(physical association)	0.400
VSTM2L	KIR2DL5A	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): KIR2DS1 (Affinity Capture-MS), KIR2DS1 (Affinity Capture-MS), KIR2DS1 (Affinity Capture-MS), KIR2DL5A (Reconstituted Complex), KIR2DS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KBC9, A1YIY0, B6A8R8, C0HJX2, C0HJX3, D3ZQX2, P08101, P0C1X9, P0DTI4, P12314, P12318, P26151, P43626, P43627, P43628, P43629, P43630, P43631, P43632, P83555, P83556, P97484, Q01965, Q13291, Q14943, Q14952, Q14953, Q14954, Q28942, Q3B8P2, Q60513, Q61450, Q63203, Q64281, Q68SN8, Q6UX27, Q7TQA1, Q7Z6M3, Q8BG84, Q8BHK6

Diamond homologs: A0A0G2KBC9, A6NI73, C0HJX2, C0HJX3, D3ZQX2, O75019, O75022, O75023, O76036, P0C191, P24071, P43626, P43629, P43630, P59901, P83556, P97484, Q14943, Q14954, Q61450, Q64281, Q6GTX8, Q6ISS4, Q6PI73, Q7TQA1, Q863H2, Q8C567, Q8IYS5, Q8MJZ2, Q8MJZ7, Q8N109, Q8N149, Q8N423, Q8N6C8, Q8N743, Q8NHJ6, Q8NHK3, Q8NHL6, Q95JB9, Q9HCN6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

0 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002510093 (19:54831661 T>C), RS1008126512 (19:54832536 C>T), RS1009463547 (19:54832428 G>A), RS1011577906 (19:54832084 T>C), RS1013373429 (19:54831237 A>T), RS1014639402 (19:54831164 T>C), RS1020319741 (19:54832118 G>A,C), RS1020378744 (19:54831820 C>T), RS1025258444 (19:54831630 A>C), RS1030423538 (19:54832139 G>C), RS1030827307 (19:54832469 C>A,G), RS1032275817 (19:54831734 T>A,C), RS1036028661 (19:54831542 AT>A), RS1040983728 (19:54831414 C>A,T), RS10423866 (19:54833141 T>C,G)

Disease associations

OMIM: gene MIM:605305 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
Air Pollutants	increases expression	1
Arsenic	affects expression	1
Endosulfan	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.