KIR3DL1

Summary

KIR3DL1 (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1, HGNC:6338) is a protein-coding gene on chromosome 19q13.42, encoding Killer cell immunoglobulin-like receptor 3DL1 (P43629). Receptor on natural killer (NK) cells for HLA Bw4 allele.

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 3811 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 91 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_013289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6338
Approved symbol	KIR3DL1
Name	killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	cl-2, NKB1, cl-11, nkat3, NKB1B, AMB11, CD158e1/2, CD158E1, CD158e2
Ensembl gene	ENSG00000167633
Ensembl biotype	protein_coding
OMIM	604946
Entrez	3811

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000326542, ENST00000358178, ENST00000391728

RefSeq mRNA: 1 — MANE Select: NM_013289 NM_013289

CCDS: CCDS42621

Canonical transcript exons

ENST00000391728 — 9 exons

Exon	Start	End
ENSE00001432610	54830099	54830778
ENSE00002436240	54825028	54825078
ENSE00002436696	54829361	54829465
ENSE00002461639	54818315	54818599
ENSE00002481952	54816468	54816534
ENSE00002494103	54817534	54817569
ENSE00002505780	54821565	54821858
ENSE00002513303	54829928	54829980
ENSE00002522415	54819713	54820012

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 84.78.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	84.78	gold quality
buccal mucosa cell	CL:0002336	69.12	gold quality
blood	UBERON:0000178	66.32	gold quality
spleen	UBERON:0002106	58.26	gold quality
tibialis anterior	UBERON:0001385	52.37	silver quality
deltoid	UBERON:0001476	52.20	gold quality
pancreatic ductal cell	CL:0002079	49.87	silver quality
epithelial cell of pancreas	CL:0000083	49.44	gold quality
bone marrow cell	CL:0002092	49.44	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
right lung	UBERON:0002167	49.23	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
quadriceps femoris	UBERON:0001377	49.03	gold quality
upper lobe of left lung	UBERON:0008952	49.03	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
ileal mucosa	UBERON:0000331	48.18	silver quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF5, DNMT1, E2F1, ELF1, FOS, MYC, MZF1, NFKB, RUNX3, YY1

miRNA regulators (miRDB)

27 targeting KIR3DL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-18B-3P	98.05	65.55	595
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-643	97.35	67.91	805
HSA-MIR-4671-5P	97.10	65.70	93
HSA-MIR-3157-3P	95.86	67.08	454

Literature-anchored findings (GeneRIF, showing 40)

• KIR inhibits activation-induced cell death by blocking Fas ligand induction upon stimulation in a process apparently accomplished by protein kinase C (PKC) recruitment to the membrane-proximal PKC binding site and subsequent inhibition of PKC activation. (PMID:12244166)
• Allele-specific 3DL1 gene expression correlated with promoter and 5’ gene DNA hypomethylation in NK cells in vitro and in vivo. (PMID:12538663)
• Positive linkage disequilibrium was seen between KIR3DS1 and KIR2DS3, and between KIR3DS1 and KIR2DS5. (PMID:12559621)
• The promoter of KIR3DL1 exhibits variegated expression in a range of cell types, with reduced activity suggesting a requirement for other regulatory elements for physiological expression compared to the KIR2DL4 promoter. (PMID:12794136)
• isolated 3 distinct KIR2DL4 allele clones in each individual with multiple copies of KIR3DL/S1; assumption that unequal crossover event occurred between differing KIR haplotypes resulting in the duplication of the 2DL4, 3DS1/3DL1 genes (PMID:12826375)
• Analysis of recombinant mutants made between KIR3DL1*004 and KIR3DL1*002 alleles shows that polymorphism in immunoglobulin domains 0 and 1 causes intracellular retention of KIR3DL1*004, preventing cell surface expression and function. (PMID:14662867)
• Decreased expression of NKB1 and GL183 on natural killer (NK) cells in endometrium, but not in myometrium, in women with adenomyosis. May be compensatory effect in which NK cytotoxicity is activated in order to eradicate abnormal endometrial cells. (PMID:15217996)
• 4.5% of the individuals of a Caucasoid population bear a recombinant allele of KIR3DP1, officially designed KIR3DP1*004, that associates tightly with gene duplications of KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 (PMID:15580659)
• KIR3DL1 allotypes contribute to development of an inhibitory response to HLA-Bw4 ligands in transduced natural killer (NK) leukemia cell lines. (PMID:16210627)
• Presence of KIR3DS1 or KIR3DL1 in combination with HLA-B*27s/HLA-B Bw4-I80 genotypes may modulate the development of ankylosing spondylitis. (PMID:16805919)
• We took a comprehensive linker-scanning mutagenesis approach and substituted 24 consecutive 10-bp segments in the human KIR3DL1 promoter. Our analysis revealed eight segments that activated and three segments that repressed KIR transcription. (PMID:16818466)
• This study shows that HLA-A*2402 is a ligand for KIR3DL1 and demonstrates how the binding of KIR3DL1 to Bw4(+) ligands depends upon the bound peptide as well as HLA and KIR3DL1 polymorphism. (PMID:17182537)
• Inhibitory alleles of KIR3DL1 differ in their ability to recognize HLA-Bw4 ligand, and a consistent hierarchy of ligand reactivity can be defined. (PMID:17182560)
• 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)
• Frequency of HLA-Bw4 and -C2, which are ligands for the inhibitory KIRs 3DL1 and 2DL1, respectively, was significantly reduced in Primary sclerosing cholangitis patients as compared with controls (PMID:17383044)
• This report is comparing KIR genotyping distribution in two Arab populations that sheds additional light on the importance of this gene in delineating a possible geographic genetic demarcation among different ethnicities. (PMID:17385087)
• 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)
• Maternal KIR/fetal HLA-Cw gene combinations that are involved in the fetomaternal tolerance do not appear to play a role in the HPA-1a alloimmunization. (PMID:17714418)
• KIR donor-recipient genotype is not predictive for the outcome of unrelated-donor hematopoietic stem cell tranplantation in patients with beta-Thalassemia. (PMID:17950922)
• various sequence motifs are implicated in the PKC-mediated post-transcriptional upregulation of KIR, and each of these motifs work in different steps after PKC activation (PMID:18301382)
• 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)
• E2F1 contributes to the transcriptional activation of the KIR3DL1 gene. (PMID:18358829)
• analysis of the ability of most common HLA-B alleles and HLA-A alleles with Bw4 serologic reactivity to protect target cells from lysis by KIR3DL1-dependent NK cells (PMID:18385451)
• KIR3DL1 evolution maintains variation in KIR3DL1 cell-surface expression levels, potentially due to the effect of such variation on functional capacity. (PMID:18453594)
• expression of HLA A*2301, A*2402, or A*3201 but not HLA A*2501 protects target cells from lysis by KIR3DL1(+) NK cells (PMID:18502829)
• The HLA-Cw*0701 allele and KIR haplotype AA are associated with AMD. This genotype combination suggests that natural killer cells have a role in the pathogenesis of AMD. (PMID:18515573)
• kir3dl1 expression in K562 cells is regulated by DNA methylation. (PMID:18549610)
• Genetic interactions of KIR and G1M immunoglobulin allotypes differ in obese and non-obese individuals with type 2 diabetes. (PMID:18632158)
• 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)
• There may be a association between the polymorphism of KIR genes with systemic lupus erythematosus in North of China. (PMID:18687225)
• plays a role in the regulation of GVHD and GVL. (review) (PMID:18800608)
• Polymorphism at sites throughout the human leukocyte antigen (HLA) class I molecule can influence the interaction of the HLA Bw4 epitope with KIR3DL1. (PMID:18941220)
• Our data suggest that extensive KIR gene polymorphisms are ubiquitous as well as quite complex. (PMID:19000148)
• The frequency of KIR3DL1/S1 subtype expression on NK cells contribute to the phenotypic variation across allotypes with respect to disease resistance. (PMID:19008943)
• KIR/HLA genotype and expression of NKG2C and NKG2D might play a significant role in regulating natural killer cell function and anti-cytomegalovirus immunity after kidney transplantation. (PMID:19032228)
• The aim of this study was to explore the possibility of the inheritance of KIR genotypes and haplotypes as a candidate for susceptibility to persistent hepatitis B virus (HBV) infection or HBV clearance. (PMID:19118512)
• The quantity of HLA-I expression on precursor-B-ALL blast regulates overall NK cell susceptibility; in case of reduced HLA expression, differential surface expression of killer cell Ig-like receptor affects NK cell alloreactivity against those blasts. (PMID:19151793)
• To assess whether KIR ligands, KIR genes and KIR haplotypes are associated with HSCT outcome of 124 patients with various hematological malignancies, transplanted with 12/12 HLA matched grafts from unrelated donors. (PMID:19169284)
• E2F1 participates in the regulation of the transcriptional activation of the KIR3DL1 gene. (PMID:19176033)
• Persistence of KIR3DS1+ and KIR3DL1+ NK cells during acute HIV1 infection is HLA class I-dependent. (PMID:19386717)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kir3dl1	ENSMUSG00000031424
mus_musculus	Kir3dl2	ENSMUSG00000057439
rattus_norvegicus	Kir3dl1	ENSRNOG00000027843

Paralogs (25): GP6 (ENSG00000088053), LILRB1 (ENSG00000104972), LILRA1 (ENSG00000104974), LILRB5 (ENSG00000105609), A1BG (ENSG00000121410), KIR2DL1 (ENSG00000125498), LILRB2 (ENSG00000131042), IGSF1 (ENSG00000147255), LAIR2 (ENSG00000167618), OSCAR (ENSG00000170909), FCAR (ENSG00000186431), LILRB4 (ENSG00000186818), LILRA5 (ENSG00000187116), KIR2DL4 (ENSG00000189013), VSTM1 (ENSG00000189068), NCR1 (ENSG00000189430), LILRB3 (ENSG00000204577), KIR2DS4 (ENSG00000221957), LILRA4 (ENSG00000239961), LILRA2 (ENSG00000239998), KIR3DL2 (ENSG00000240403), KIR3DL3 (ENSG00000242019), KIR2DL3 (ENSG00000243772), LILRA6 (ENSG00000244482), TARM1 (ENSG00000248385)

Protein

Protein identifiers

Killer cell immunoglobulin-like receptor 3DL1 — P43629 (reviewed: P43629)

Alternative names: CD158 antigen-like family member E, HLA-BW4-specific inhibitory NK cell receptor, Natural killer-associated transcript 3, p70 natural killer cell receptor clones CL-2/CL-11

All UniProt accessions (3): P43629, Q5UCE2, W5QJC1

UniProt curated annotations — full annotation on UniProt →

Function. Receptor on natural killer (NK) cells for HLA Bw4 allele. Inhibits the activity of NK cells thus preventing cell lysis.

Subcellular location. Cell membrane.

Domain organisation. Ig-like C2-type domain 2 mediates specificity through recognition of the Bw4 epitope.

Similarity. Belongs to the immunoglobulin superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P43629-1	1	yes
P43629-2	2

RefSeq proteins (1): NP_037421* (*=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 (66 total): strand 31, sequence variant 11, region of interest 3, glycosylation site 3, disulfide bond 3, helix 3, domain 3, topological domain 2, turn 2, signal peptide 1, chain 1, compositionally biased region 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
9D97	X-RAY DIFFRACTION	1.6
9BL4	X-RAY DIFFRACTION	1.75
3VH8	X-RAY DIFFRACTION	1.8
6V3J	X-RAY DIFFRACTION	1.98
3WUW	X-RAY DIFFRACTION	2
5T6Z	X-RAY DIFFRACTION	2
7K81	X-RAY DIFFRACTION	2
9BL3	X-RAY DIFFRACTION	2
9BL5	X-RAY DIFFRACTION	2
5T70	X-RAY DIFFRACTION	2.1
9BL2	X-RAY DIFFRACTION	2.1
5B38	X-RAY DIFFRACTION	2.3
7K80	X-RAY DIFFRACTION	2.4
9BL6	X-RAY DIFFRACTION	2.4
9D96	X-RAY DIFFRACTION	2.4
5B39	X-RAY DIFFRACTION	2.5
9BL9	X-RAY DIFFRACTION	2.6
9BLA	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43629-F1	75.75	0.48

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): 92, 179, 273

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 74 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_64, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, MODULE_70, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, MODULE_99, KEGG_GRAFT_VERSUS_HOST_DISEASE, GNF2_IL2RB, GOBP_NATURAL_KILLER_CELL_MEDIATED_IMMUNITY, GOBP_IMMUNE_EFFECTOR_PROCESS, GOBP_CELL_KILLING

GO Biological Process (3): immune response-regulating signaling pathway (GO:0002764), immune response (GO:0006955), natural killer cell mediated cytotoxicity (GO:0042267)

GO Molecular Function (3): HLA-B specific inhibitory MHC class I receptor activity (GO:0030109), molecular adaptor activity (GO:0060090), 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
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
signal transduction	1
regulation of immune response	1
immune system process	1
response to stimulus	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
inhibitory MHC class I receptor activity	1
molecular_function	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIR3DL1	HLA-B	P01889	998
KIR3DL1	HLA-A	P01891	997
KIR3DL1	HLA-C	P04222	990
KIR3DL1	F8W876	F8W876	829
KIR3DL1	KLRC1	P26715	811
KIR3DL1	TYROBP	O43914	805
KIR3DL1	HLA-E	P13747	805
KIR3DL1	FCN3	O75636	803
KIR3DL1	FCN2	Q15485	802
KIR3DL1	FCN1	O00602	801
KIR3DL1	NCAM1	P13591	797
KIR3DL1	KLRD1	Q13241	792
KIR3DL1	TRIM45	Q9H8W5	773
KIR3DL1	SORBS1	Q9BX66	773
KIR3DL1	MASP2	O00187	772

IntAct

45 interactions, top by confidence:

A	B	Type	Score
HLA-B	IGKC	psi-mi:“MI:0915”(physical association)	0.800
KIR3DL1	HLA-F	psi-mi:“MI:0915”(physical association)	0.680
HLA-F	KIR3DL1	psi-mi:“MI:0407”(direct interaction)	0.680
KIR3DL1	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
THSD7B	KIR3DL1	psi-mi:“MI:0915”(physical association)	0.560
BMP10	KIR3DL1	psi-mi:“MI:0915”(physical association)	0.560
KIR3DL1	FAM114A2	psi-mi:“MI:0915”(physical association)	0.560
KIR2DS2	RHOBTB3	psi-mi:“MI:0914”(association)	0.530
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
HLA-B	KIR3DL1	psi-mi:“MI:0915”(physical association)	0.400
HLA-A	nef	psi-mi:“MI:0915”(physical association)	0.400
HLA-B	gag	psi-mi:“MI:0915”(physical association)	0.400
KIR3DL1	HLA-B	psi-mi:“MI:0915”(physical association)	0.400
HLA-A	KIR3DL1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (16): KIR3DL1 (Affinity Capture-MS), KIR2DL2 (Affinity Capture-MS), FAM114A2 (Affinity Capture-MS), KIR2DL2 (Affinity Capture-MS), KIR3DL1 (Affinity Capture-MS), FAM114A2 (Affinity Capture-MS), KIR3DL1 (Two-hybrid), KIR3DL1 (Two-hybrid), KIR3DL1 (Two-hybrid), KIR3DL1 (Affinity Capture-MS), KIR3DL1 (Affinity Capture-MS), FAM114A2 (Affinity Capture-MS), PCDH1 (Affinity Capture-MS), KIR3DL1 (Reconstituted Complex), KIR3DL1 (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

8 interactions.

A	Effect	B	Mechanism
CSNK1D	up-regulates	KIR3DL1	phosphorylation
PRKCE	down-regulates	KIR3DL1	phosphorylation
PRKCG	down-regulates	KIR3DL1	phosphorylation
CSNK2A1	“up-regulates quantity by stabilization”	KIR3DL1	phosphorylation
PRKCB	“down-regulates activity”	KIR3DL1	phosphorylation
PRKCA	“down-regulates activity”	KIR3DL1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
immune response	6	18.8×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1137 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54818477:A:T	donor_gain	1.0000
19:54818517:G:T	donor_gain	1.0000
19:54829358:CAG:C	acceptor_loss	1.0000
19:54829359:A:AG	acceptor_gain	1.0000
19:54829359:A:AT	acceptor_loss	1.0000
19:54829359:AG:A	acceptor_gain	1.0000
19:54829360:G:GA	acceptor_gain	1.0000
19:54829360:GG:G	acceptor_gain	1.0000
19:54829360:GGT:G	acceptor_gain	1.0000
19:54829360:GGTA:G	acceptor_gain	1.0000
19:54829360:GGTAA:G	acceptor_gain	1.0000
19:54829461:AAAAA:A	donor_gain	1.0000
19:54829462:AAAA:A	donor_gain	1.0000
19:54829463:AAA:A	donor_gain	1.0000
19:54829464:AA:A	donor_gain	1.0000
19:54829464:AAGT:A	donor_loss	1.0000
19:54829465:AGTAA:A	donor_loss	1.0000
19:54829466:G:GG	donor_gain	1.0000
19:54829467:TAAGT:T	donor_loss	1.0000
19:54829978:GAGGT:G	donor_loss	1.0000
19:54829981:G:GA	donor_loss	1.0000
19:54829982:T:G	donor_loss	1.0000
19:54830094:TCCAG:T	acceptor_loss	1.0000
19:54830097:A:AG	acceptor_gain	1.0000
19:54830098:G:GG	acceptor_gain	1.0000
19:54830098:G:GT	acceptor_loss	1.0000
19:54816531:GTTG:G	donor_gain	0.9900
19:54816534:GGTG:G	donor_loss	0.9900
19:54816535:G:GG	donor_gain	0.9900
19:54816535:GTG:G	donor_loss	0.9900

AlphaMissense

2906 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54819985:A:C	S210R	0.967
19:54819987:T:A	S210R	0.967
19:54819987:T:G	S210R	0.967
19:54821831:A:C	S308R	0.950
19:54821833:T:A	S308R	0.950
19:54821833:T:G	S308R	0.950
19:54821747:T:C	F280L	0.938
19:54821749:C:A	F280L	0.938
19:54821749:C:G	F280L	0.938
19:54819787:T:A	C144S	0.931
19:54819788:G:C	C144S	0.931
19:54819814:T:C	F153L	0.931
19:54819816:C:A	F153L	0.931
19:54819816:C:G	F153L	0.931
19:54819805:T:C	F150L	0.930
19:54819807:T:A	F150L	0.930
19:54819807:T:G	F150L	0.930
19:54819940:T:A	C195S	0.921
19:54819941:G:C	C195S	0.921
19:54818572:A:C	S110R	0.919
19:54818574:C:A	S110R	0.919
19:54818574:C:G	S110R	0.919
19:54819787:T:C	C144R	0.917
19:54819986:G:T	S210I	0.916
19:54818389:T:A	C49S	0.914
19:54818390:G:C	C49S	0.914
19:54818430:A:C	K62N	0.914
19:54818430:A:T	K62N	0.914
19:54821748:T:G	F280C	0.911
19:54821789:T:C	F294L	0.909

dbSNP variants (sampled 300 via entrez): RS1000052124 (19:54815910 G>A), RS1000168776 (19:54821517 T>C), RS1000267190 (19:54821110 T>C), RS1001413674 (19:54753670 G>A), 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)

Disease associations

OMIM: gene MIM:604946 | disease phenotypes: MIM:148300, MIM:231090

GenCC curated gene-disease

Mondo (3): prostate cancer (MONDO:0008315), keratoconus (MONDO:0015486), hydatidiform mole, recurrent, 1 (MONDO:0009273)

Orphanet (5): Familial prostate cancer (Orphanet:1331), Complete hydatidiform mole (Orphanet:254688), Hydatidiform mole (Orphanet:99927), OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000563	Keratoconus

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004133_69	Ulcerative colitis	1.000000e-07
GCST90002388_382	Lymphocyte count	3.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007640	Keratoconus	C11.204.627
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Azacitidine	decreases methylation, increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
CGP 52608	affects binding, increases reaction	1
Arsenic	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Formaldehyde	increases expression	1
Valproic Acid	increases methylation	1
Zinc	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer