KIR3DS1

Summary

KIR3DS1 (killer cell immunoglobulin like receptor, three Ig domains and short cytoplasmic tail 1, HGNC:6340) is a protein-coding gene on chromosome 19q13.4 alternate reference locus, encoding Killer cell immunoglobulin-like receptor 3DS1 (Q14943). Receptor on natural killer (NK) cells for MHC class I molecules.

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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3813 — RefSeq curated summary.

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6340
Approved symbol	KIR3DS1
Name	killer cell immunoglobulin like receptor, three Ig domains and short cytoplasmic tail 1
Location	19q13.4 alternate reference locus
Locus type	gene with protein product
Status	Approved
Aliases	nkat10
Ensembl gene	ENSG00000275434
OMIM	620778
Entrez	3813

Gene structure

Transcript identifiers

Ensembl transcripts: 0

RefSeq mRNA: 2 — MANE Select: None NM_001282170, NM_001282171

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 40)

• In 3DS1/3DL1 heterozygous donors significant numbers of natural killer (NK) cells express 3DS1 without co-expressing 3DL1 and that NK cells expressing both alleles are difficult to detect. (PMID:17301953)
• Carriage of activating 3ds1 was increased in patients with herpes virus RDs. (PMID:17592337)
• Sequencing analysis identified a variant with a complex deletion/substitution mutation in exon 4 (which encodes the D1 extracellular domain), resulting in a premature stop codon and might affect its expression and activating capacity (PMID:17687550)
• KIR3DL1/S1 is under balancing selection in most human populations except Africans. KIR3DL1/S1 is co-evolving with Bw4 ligand of HLA-A and B. (PMID:17694054)
• Variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication. (PMID:18025129)
• We observed that possessing KIR3DS1 was associated with higher NK cell effector functions in early HIV-1 disease, despite the absence of HLA Bw4Ile80, a putative ligand of KIR3DS1. (PMID:18305035)
• in bone marrow transplant patients alleles 3DL1*00101 & *002 were most frequently observed in addition to 12 other known 3DL1 alleles; A single 3DS1 allele, 3DS1*01301, was identified; two new alleles, 3DL1*01702 and 3DS1*058, were characterized (PMID:18331531)
• 3DL1/3DS1 demonstrated an increased frequency in ankylosing spondylitis (p(c) < 0.005 in the Chinese population and p(c) < 0.05 in the Thai population) (PMID:18638658)
• The frequency of KIR3DL1/S1 subtype expression on NK cells contribute to the phenotypic variation across allotypes with respect to disease resistance. (PMID:19008943)
• Persistence of KIR3DS1+ and KIR3DL1+ NK cells during acute HIV1 infection is HLA class I-dependent. (PMID:19386717)
• KIR3DS1 expression on NK cells can be induced after exposure to stimulator cells (PMID:19454667)
• Data revealed that the trend of parasitic positive individuals to be KIR3DL1/KIR3DS1 heterozygous in pair with KIR2DS4 nondeleted variants in a set of KIR genes inheritable as the AB genotypes. (PMID:19859704)
• KIR3DS1 and KIR2DS1 may be necessary to trigger an effective early immune response against HPV-infected targets to establish resistance to recurrent respiratory papillomatosis (PMID:19861144)
• no association in frequencies of the alleles of these gene in ankylosing spondylitis (PMID:19874556)
• individuals carrying three activating KIR genes 3DS1, 2DS1, and 2DS5 are more frequent in patients with Vogt-Koyanagi-Harada disease than in controls (PMID:19897003)
• Compared with KIR3DS1(-) donors, donor KIR3DS1 was associated with lower-grade II-IV acute graft-versus-host disease. (PMID:20124216)
• The increased frequency of the KIR3DS1*013 allele in patients with amnkylosing spondylitis is clearly independent of the presence of the HLA-Bw4I80 epitope. (PMID:20131260)
• KIR3DL1 and KIR3DS1 allele frequencies were determined by DNA sequencing of the complete coding regions from 100 random unrelated African Americans (PMID:20230527)
• The most significant difference in PFS observed in multiple myeloma patients after autologous stem cell transplantation was with those with GR KIR3DS1(+) in whom HLA-Bw4, the ligand for the corresponding inhibitory receptor KIR3DL1, was missing (PMID:20562327)
• predisposition to systemic lupus erythematosus was associated with GTGT deletion at the SLC11A1 3’UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes and European and Amerindian ancestries (PMID:21233146)
• Our results that KIR2DL5 and KIR3DS1 may have a predisposing role in multiple sclerosis (PMID:21665278)
• There is evidence of the association of activating KIR genotypes with an increased risk for autoimmune disease (PMID:21779711)
• These data provide the first evidence for the direct binding of KIR3DS1(+) cells to HLA-Bw4 and highlight the key role for position 138 in determining ligand specificity of KIR3DS1 (PMID:21804024)
• Data suggest that low level of activating KIR3DS1 and its combination with HLA-B Bw4Ile80 ligand might have an influence on the susceptibility to tuberculosis (TB) in Lur population of Iran. (PMID:22426166)
• Data 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)
• Data found that the frequencies of KIR2DS1, 2DS3 and 3DS1 were significantly higher in pulmonary tuberculosis patients than in the control group. (PMID:22653583)
• KIR3DS1, in addition to HLA-B27, may play an important independent role in the pathogenesis of ankylosing spondylitis in the Chinese population. (PMID:22744805)
• Our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human natural killer cells. (PMID:23325834)
• Report reliable and accurate method for genotyping KIR3DL1/S1 using DNA recovered from plasma. (PMID:23524032)
• Results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates. (PMID:23613999)
• results suggest that the sole presence of KIR3DS1 could have a protective role in HIV-1 infection in highly exposed and persistently seronegative individuals (PMID:23789883)
• Different KIR3DS1, KIR3DL1 and HLA-Bw4 genotypes and levels of transcripts associate with HIV disease progression. (PMID:24059286)
• KIR2DL3 and KIR3DS1 genes could be protector genes and immuno-genetic markers for Hepatits B in the Turkish population. (PMID:24407110)
• Protective genotypes in HIV infection reflect superior function of KIR3DS1 over KIR3DL1-expressing CD8+ T cells. (PMID:25112829)
• Data show that KIR2DL5 receptor, KIR2DS1 protein, KIR2DS5 protein and KIR3DS1 receptors were all significantly associated with high viral load. (PMID:25253288)
• Moreover, the frequency of activating genotypes in the AS patient group was significantly higher than in the healthy control group (P < 0.05). KIR2DS1 and KIR3DS1 (PMID:25491925)
• genetic polymorphism is not related to acute myeloid leukemia in Chinese population (PMID:25636577)
• The data from this study contribute novel insight into how KIR3DS1-specific polymorphisms in the extracellular region impact KIR3DL1 surface expression, ligand binding, and inhibitory function. (PMID:26109640)
• genetic polymorphism is associated with childhood acute lymphoblastic leukemia among north Indians (PMID:26472014)
• evidence that KIR-regulated signaling contributes to Behcet’s disease (PMID:27708262)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Killer cell immunoglobulin-like receptor 3DS1 — Q14943 (reviewed: Q14943)

Alternative names: Natural killer-associated transcript 10

All UniProt accessions (1): Q14943

UniProt curated annotations — full annotation on UniProt →

Function. Receptor on natural killer (NK) cells for MHC class I molecules. Upon interaction with peptide-free HLA-F open conformer, triggers NK cell degranulation and anti-viral cytokine production.

Subunit / interactions. Interacts with HLA-F open conformer; this interaction is direct.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in NK and T-cell lines but not in B-lymphoblastoid cell lines or in a colon carcinoma cell line.

Polymorphism. The KIR genes are located in a segment of DNA on 19q13.4 in the leukocyte receptor complex that has undergone expansion and contraction over time, probably through unequal crossing-over. Thus, KIR haplotypes vary in the number and types of genes, although a few framework loci, such as the gene KIR3DL1, are present on all or nearly all haplotypes. KIR3DL1 and KIR3DS1 segregate as alleles of the locus KIR3DL1/3DS1.

Similarity. Belongs to the immunoglobulin superfamily.

RefSeq proteins (2): NP_001269099, NP_001269100 (*=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 (24 total): sequence variant 10, glycosylation site 3, disulfide bond 3, domain 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14943-F1	81.05	0.55

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 (3): 49–95, 144–195, 244–293

Glycosylation sites (3): 273, 92, 179

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2172127	DAP12 interactions
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 24 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NATURAL_KILLER_CELL_ACTIVATION, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_IMMUNE_RESPONSE_INHIBITING_SIGNAL_TRANSDUCTION, GOBP_LYMPHOCYTE_ACTIVATION, GOMF_MHC_CLASS_I_RECEPTOR_ACTIVITY, REACTOME_DAP12_INTERACTIONS, GOMF_IMMUNE_RECEPTOR_ACTIVITY, GOBP_IMMUNE_RESPONSE_REGULATING_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY, GSE22045_TREG_VS_TCONV_UP, GSE22886_NAIVE_TCELL_VS_NKCELL_DN, GSE22886_NAIVE_CD8_TCELL_VS_NKCELL_DN, GSE2706_R848_VS_LPS_8H_STIM_DC_UP

GO Biological Process (3): immune response-regulating signaling pathway (GO:0002764), immune response (GO:0006955), natural killer cell activation (GO:0030101)

GO Molecular Function (2): MHC class I receptor activity (GO:0032393), protein binding (GO:0005515)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	1
regulation of immune response	1
immune system process	1
response to stimulus	1
lymphocyte activation	1
transmembrane signaling receptor activity	1
MHC class I protein binding	1
immune receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

34 interactions, top by confidence:

A	B	Type	Score
HLA-B	B2M	psi-mi:“MI:0915”(physical association)	0.930
HLA-C	B2M	psi-mi:“MI:0915”(physical association)	0.880
HLA-B	IGKC	psi-mi:“MI:0915”(physical association)	0.800
KIR3DS1	HLA-F	psi-mi:“MI:0915”(physical association)	0.710
HLA-F	KIR3DS1	psi-mi:“MI:0407”(direct interaction)	0.710
KIR3DS1	PPL	psi-mi:“MI:0914”(association)	0.530
HLA-B	nef	psi-mi:“MI:0915”(physical association)	0.400
HLA-B	gag-pol	psi-mi:“MI:0915”(physical association)	0.400
KIR3DS1	HLA-A	psi-mi:“MI:0915”(physical association)	0.400
KIR3DS1	HLA-B	psi-mi:“MI:0915”(physical association)	0.400
HLA-A	B2M	psi-mi:“MI:0915”(physical association)	0.400
KIR3DS1	HLA-C	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (65): KLK7 (Affinity Capture-MS), CALML5 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), TGM3 (Affinity Capture-MS), RNASE7 (Affinity Capture-MS), CALML3 (Affinity Capture-MS), POF1B (Affinity Capture-MS), SERPINB7 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), FLG (Affinity Capture-MS), GM2A (Affinity Capture-MS), KIR2DL2 (Affinity Capture-MS), ALOX12B (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): RS1000052124 (19:54815910 G>A), RS1000168776 (19:54821517 T>C), RS1000267190 (19:54821110 T>C), RS1001893593 (19:54815042 C>T), RS1001937254 (19:54822654 T>C), RS1002509663 (19:54828074 T>C), RS1002965796 (19:54817295 G>A), RS1003158637 (19:54819317 C>G), RS1003508705 (19:54814746 G>A,C), RS1003514479 (19:54825396 A>C,G), RS1004279407 (19:54829220 A>G,T), RS1005241841 (19:54820742 G>A), RS1005909444 (19:54823972 G>A,C), RS1006558463 (19:54826618 C>A,G), RS1006740520 (19:54817218 G>A,T)

Disease associations

OMIM: gene MIM:620778 | 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

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	decreases expression	1
Bortezomib	decreases expression	1
Smoke	increases expression	1

Clinical trials (associated diseases)

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