KIR2DL5B

Summary

KIR2DL5B (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 5B, HGNC:16346) is a protein-coding gene on chromosome 19q13.4 alternate reference locus, encoding Killer cell immunoglobulin-like receptor 2DL5B (Q8NHK3). 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 553128 — RefSeq curated summary.

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16346
Approved symbol	KIR2DL5B
Name	killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 5B
Location	19q13.4 alternate reference locus
Locus type	gene with protein product
Status	Approved
Aliases	KIR2DL5.2, KIR2DL5, KIR2DL5.3, KIR2DL5.4
OMIM	615727
Entrez	553128

Gene structure

Transcript identifiers

Ensembl transcripts: 0

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

None — 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 7)

• Association of KIR2DL5B gene with celiac disease supports the susceptibility locus on 19q13.4. (PMID:17215859)
• 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)
• KIR2DL3, KIR2DS5 and KIR2DL5B genes may be correlated with pathogenesis of nasopharyngeal carcinoma in the Chinese southern Han population. (PMID:21729574)
• 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)
• We found the presence of KIR2DL5B to be associated with inferior transformation-free survival and event-free survival in patients with chronic phase-chronic myeloid leukemia (PMID:26500342)
• KIR2DL5B and HLA DRB1*12 alleles seems to be associated with protection against HIV-1 in serodiscordant couples in Burkina Faso. (PMID:35501290)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Killer cell immunoglobulin-like receptor 2DL5B — Q8NHK3 (reviewed: Q8NHK3)

Alternative names: CD158 antigen-like family member F2, Killer cell immunoglobulin-like receptor 2DLX

All UniProt accessions (0):

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 (0): (*=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 (18 total): sequence variant 3, compositionally biased region 2, disulfide bond 2, topological domain 2, domain 2, region of interest 2, signal peptide 1, chain 1, glycosylation site 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHK3-F1	72.12	0.40

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 (1): 218

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 8 (showing top): GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_IMMUNE_RESPONSE_INHIBITING_SIGNAL_TRANSDUCTION, GOMF_IMMUNE_RECEPTOR_ACTIVITY, GOBP_IMMUNE_RESPONSE_REGULATING_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_IMMUNE_SYSTEM_PROCESS, GOMF_MOLECULAR_TRANSDUCER_ACTIVITY

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

GO Molecular Function (0):

GO Cellular Component (1): plasma membrane (GO:0005886)

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

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

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): RS1001413674 (19:54753670 G>A), RS1011377084 (19:54753914 A>G), RS1022363799 (19:54753915 T>C), RS1022860612 (19:54753383 C>G), RS1029872281 (19:54753972 T>C), RS1033599658 (19:54753739 T>C), RS1033674621 (19:54753229 T>C), RS10422679 (19:54753963 A>T), RS10423983 (19:54754310 G>A,C,T), RS111841886 (19:54753969 T>G), RS114861744 (19:54753612 C>A,T), RS1156871204 (19:54753434 G>T), RS1156883326 (19:54754430 G>A), RS1157399369 (19:54753217 A>G), RS1159106814 (19:54754270 C>T)

Disease associations

OMIM: gene MIM:615727 | 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

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Amiodarone	increases expression	1

Clinical trials (associated diseases)

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