KIR2DL3

Summary

KIR2DL3 (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3, HGNC:6331) is a protein-coding gene on chromosome 19q13.42, encoding Killer cell immunoglobulin-like receptor 2DL3 (P43628). Receptor on natural killer (NK) cells for HLA-C alleles (HLA-Cw1, HLA-Cw3 and HLA-Cw7).

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 3804 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 79 total
• Druggable target: yes
• MANE Select transcript: NM_015868

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6331
Approved symbol	KIR2DL3
Name	killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	cl-6, nkat2, nkat2a, nkat2b, p58, CD158B2
Ensembl gene	ENSG00000243772
Ensembl biotype	protein_coding
OMIM	604938
Entrez	3804

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000342376, ENST00000880264

RefSeq mRNA: 1 — MANE Select: NM_015868 NM_015868

CCDS: CCDS33107

Canonical transcript exons

ENST00000342376 — 8 exons

Exon	Start	End
ENSE00001390104	54752367	54753052
ENSE00001940903	54738513	54738579
ENSE00002430598	54739507	54739542
ENSE00002443924	54741980	54742279
ENSE00002459035	54747335	54747385
ENSE00002464524	54752216	54752268
ENSE00002466251	54743795	54744088
ENSE00002511493	54751649	54751753

Expression profiles

Bgee: expression breadth broad, 43 present calls, max score 89.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1075 / max 45.1925, expressed in 30 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177547	0.1075	30
177548	0.1007	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.13	gold quality
granulocyte	CL:0000094	81.50	gold quality
blood	UBERON:0000178	71.44	gold quality
spleen	UBERON:0002106	59.00	gold quality
bone marrow	UBERON:0002371	55.06	gold quality
bone marrow cell	CL:0002092	51.54	gold quality
right lung	UBERON:0002167	50.83	gold quality
endometrium	UBERON:0001295	49.66	gold quality
placenta	UBERON:0001987	48.24	gold quality
upper lobe of left lung	UBERON:0008952	47.79	gold quality
lung	UBERON:0002048	47.11	gold quality
leukocyte	CL:0000738	45.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	44.29	gold quality
smooth muscle tissue	UBERON:0001135	42.83	silver quality
monocyte	CL:0000576	42.31	gold quality
liver	UBERON:0002107	41.78	silver quality
right lobe of liver	UBERON:0001114	41.69	silver quality
gall bladder	UBERON:0002110	41.10	gold quality
muscle tissue	UBERON:0002385	40.89	silver quality
skeletal muscle tissue	UBERON:0001134	40.85	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
omental fat pad	UBERON:0010414	37.13	gold quality
lymph node	UBERON:0000029	37.09	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
adipose tissue	UBERON:0001013	36.43	silver quality
subcutaneous adipose tissue	UBERON:0002190	35.76	silver quality
hindlimb stylopod muscle	UBERON:0004252	35.75	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
myometrium	UBERON:0001296	34.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1

miRNA regulators (miRDB)

24 targeting KIR2DL3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4326	98.97	67.63	962
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-3144-5P	97.64	65.45	646
HSA-MIR-643	97.35	67.91	805
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539

Literature-anchored findings (GeneRIF, showing 40)

• HLA-Cw7 zygosity affects the size of a subset of CD158b+ natural killer cells. (PMID:11958591)
• Positive linkage disequilibrium was seen between KRI2DL1 and KIR2DL3.Individuals were subgrouped according to the major HLA-C encoded KIR-epitopes (group C1 versus C2). C2 individuals transcribe RNA from KIR2DL2 genes without specific HLA-C ligands. (PMID:12559621)
• 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 to eradicate abnormal endometrial cells. (GL183) (PMID:15217996)
• The modulated expression of KIR by IL-2 and TGF-beta can be associated with the changed NK-cytotoxic target-discriminating ability of NK cells upon their exposure to IL-2 and TGF-beta. (PMID:15227739)
• results show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection (PMID:15297676)
• CD158a and CD158b display a coactivatory function, involving the c-Jun NH2-terminal protein kinase signaling pathway, when expressed on malignant CD4+ T cells from a patient with Sezary syndrome (PMID:17522341)
• donor killer immunoglobulin-like receptor (KIR) genotype-patient KIR ligand combination (Mismatch) and no antithymocyte globulin preadministration are critical factors for the adverse effects of allogeneic stem cell transplantation (PMID:18158964)
• In contrast to natural killer (NK) cells, the functions of killer inhibitory receptors in CD4+ T lymphocytes might derive from a selective expression of their activating or inhibiting (CD158b2) forms. (PMID:18292496)
• Allelic polymorphism at sites distal to the ligand-binding site of KIR2DL3 has diversified this receptor’s interactions with HLA-C. No cytotoxic interaction between the HLA-C epitope and KIR2DL3 receptor is observed compared to that of KIR2DL2 and HLA-C. (PMID:18322206)
• Some KIR-HLA genotypes could be associated to the development of clinical forms of leprosy. (PMID:18778326)
• Support role for KIR2DL3 receptor in determining severity of hepatitis C virus recurrence after liver transplantation. (PMID:19326408)
• decidual CD4+ and CD8+ T cells contain increased proportions of KIR2DL3+ cells compared to peripheral blood (PMID:19394706)
• DNA-demethylating treatment with 5-azacytidine resulted in re-expression of kir2DL1 gene and increased expressions of kir2DL1, kir2DL2 and kir2DL3 genes in NK-92MI cells. (PMID:19549382)
• Findings in HCV-infected and non-infected IDUs suggest an important role for KIRs (KIR2DL2 and KIR2DL3) with group HLA-C1 molecules, in the presence of activating KIR2DS4, in protection from HCV infection. (PMID:19552960)
• Contrary to CD158a and CD158b killer immunoglobulin-like receptors (KIRs), there is a significant positive correlation of NKG2D and CD161 expression with NK cytotoxicity. (PMID:19711124)
• The KIR2DL2, KIR2DL3 genotype is predisposing to Crohn’s disease in the presence of C1 ligand. (PMID:19789864)
• This study provides an estimate of the minimal KIR-HLA system essential for long-term survival of a human population. (PMID:19837691)
• Data show that KIR activation and HLA expression density are critical determinants for the efficacy of rituximab treatment. (PMID:20056126)
• KIR and HLA-C protection in both treatment response and spontaneously resolving HCV was validated at the allelic level, in which KIR2DL3-HLA-Cw*03 was associated with sustained virological response (SVR)(P = 0.004, OR = 3.4, 95% CI = 1.5-8.7). (PMID:20077564)
• Data shoe that KIR2DL3-C1C2 combination was near-significantly associated with HAM/TSP outcome in the second stage. (PMID:20483367)
• Despite its particular monoclonal antibody reactivity, the specificity of KIR2DL3*005 for HLA-C molecules does not differ from that of other KIR2DL2/L3 alleles. (PMID:20525888)
• Inhibitory receptor KIR2DL1 in combination with HLA-C2 ligand confers susceptibility to chronic hepatitis B (CHB), whereas inhibitory receptor KIR2DL3 or KIR2DL3 homozygote in the presence of HLA-C1C1 genotype shows protection against CHB. (PMID:20643584)
• We report four novel KIR2DL2 alleles and two novel KIR2DL3 alleles identified from an East African population using sequence-based typing. (PMID:20875478)
• indicated nonspecific stimulation of natural killers, probably mediated by an increase in serum concentration of heat shock protein with a molecular weight of 70 kDa (PMID:21165439)
• KIR2DL3, KIR2DS5 and KIR2DL5B genes may be correlated with pathogenesis of nasopharyngeal carcinoma in the Chinese southern Han population. (PMID:21729574)
• Carriage of specific KIR genes in combination with specific HLA-C and IL28B variants was associated with an altered HCV treatment response. (PMID:21931540)
• We found an increase in the KIR A haplotype in tuberculosis patients compared to controls, and only KIR 2DL3 was found to be significantly more prevalent among TB patients (PMID:22118180)
• Our study indicates that the absence of the inhibitory KIR2DL3 gene is associated with an increased risk of developing multiple sclerosis in individuals carrying HLA-C1 alleles (PMID:22185807)
• These results suggest that natural selection has reduced the frequency of the KIR2DL3-HLA-C1 combination in malaria high-endemic population. (PMID:22412373)
• these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection (PMID:22715396)
• Substitutions restricted to activating KIR all reduce the avidity of KIR2DL1 and KIR2DL3, further evidence that activating KIR function often becomes subject to selective attenuation. (PMID:22772445)
• Gene frequency of KIR2DL3 is lower in subjects with rheumatoid arthritis than in control. (PMID:22960345)
• Data indicate that positive linkage disequilibrium was observed between KIR3DL1, 2DL1, 2DL3 and 2DS4 which is consistent with the associations between the constituents of A haplotypes. (PMID:23354323)
• Low frequency of KIR2DL3 is associated with nodular melanoma and in ulcerated melanoma. (PMID:23370861)
• the most common KIR2DL2/3 allelic products in European American and African American populations were evaluated (PMID:23686481)
• Higher frequency of CD158b+ natural killer cells combined with fewer activated NK cells may be associated with HCV-related chronic inflammation. (PMID:23813131)
• KIR2DL3 and KIR3DS1 genes could be protector genes and immuno-genetic markers for Hepatits B in the Turkish population. (PMID:24407110)
• HLA-C genotypes are important determinants of conjunctival scarring in trachoma and that KIR2DL2/KIR2DL3 heterozygosity further increases risk of conjunctival scarring in individuals carrying HLA-C2. (PMID:24651768)
• KIR2DL3 has previously been identified as important for clearance of the Hepatitis C virus after established infection,not found to be relevant to resistance to Hepatitis C infection. (PMID:24845613)
• We investigated the association of HLA alleles and KIR ligands according to oligoclonal band status in multiple sclerosis patients. (PMID:25037176)

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), KIR3DL1 (ENSG00000167633), 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), LILRA6 (ENSG00000244482), TARM1 (ENSG00000248385)

Protein

Protein identifiers

Killer cell immunoglobulin-like receptor 2DL3 — P43628 (reviewed: P43628)

Alternative names: CD158 antigen-like family member B2, KIR-023GB, Killer inhibitory receptor cl 2-3, NKAT2a, NKAT2b, Natural killer-associated transcript 2, p58 natural killer cell receptor clone CL-6, p58.2 MHC class-I-specific NK receptor

All UniProt accessions (3): A0A376A8L8, E3NZD8, P43628

UniProt curated annotations — full annotation on UniProt →

Function. Receptor on natural killer (NK) cells for HLA-C alleles (HLA-Cw1, HLA-Cw3 and HLA-Cw7). Inhibits the activity of NK cells thus preventing cell lysis.

Subunit / interactions. Interacts with ARRB2.

Subcellular location. Cell membrane.

Similarity. Belongs to the immunoglobulin superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P43628-1	1	yes
P43628-2	2, NKAT2a-delta-Ig2

RefSeq proteins (1): NP_056952* (*=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 (44 total): strand 17, sequence variant 11, glycosylation site 3, disulfide bond 2, topological domain 2, domain 2, signal peptide 1, chain 1, splice variant 1, transmembrane region 1, helix 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6PAG	X-RAY DIFFRACTION	2.5
8TUI	X-RAY DIFFRACTION	2.75
1B6U	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43628-F1	76.84	0.53

Antibody-complex structures (SAbDab): 1 — 8TUI

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): 49–100, 149–198

Glycosylation sites (3): 178, 211, 84

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: 50 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_IMMUNE_RESPONSE, KEGG_GRAFT_VERSUS_HOST_DISEASE, MODULE_113, KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION, HOEGERKORP_CD44_TARGETS_DIRECT_DN, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_ANTIGEN_BINDING, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_IMMUNE_RESPONSE_INHIBITING_SIGNAL_TRANSDUCTION, CYCLIN_D1_UP.V1_UP, PRC1_BMI_UP.V1_DN, KRAS.LUNG_UP.V1_UP, GOMF_IMMUNE_RECEPTOR_ACTIVITY, MIR6721_5P

GO Biological Process (2): immune response-regulating signaling pathway (GO:0002764), immune response (GO:0006955)

GO Molecular Function (4): antigen binding (GO:0003823), signaling receptor activity (GO:0038023), identical protein binding (GO:0042802), 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
molecular transducer activity	1
protein binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIR2DL3	HLA-C	P04222	999
KIR2DL3	KLRC1	P26715	944
KIR2DL3	KLRD1	Q13241	935
KIR2DL3	HLA-A	P01891	867
KIR2DL3	HLA-B	P01889	860
KIR2DL3	SORBS1	Q9BX66	814
KIR2DL3	HLA-E	P13747	780
KIR2DL3	KLRC2	P26717	769
KIR2DL3	HLA-G	P17693	768
KIR2DL3	KLRK1	P26718	728
KIR2DL3	NCR3	O14931	728
KIR2DL3	NCR2	O95944	720
KIR2DL3	NCAM1	P13591	719
KIR2DL3	DYNLT1	P63172	703
KIR2DL3	FCGR3A	P08637	692

IntAct

226 interactions, top by confidence:

A	B	Type	Score
KIR2DL3	HLA-C	psi-mi:“MI:0407”(direct interaction)	0.620
HLA-C	KIR2DL3	psi-mi:“MI:0407”(direct interaction)	0.620
BRICD5	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
SNORC	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
CYBC1	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
CDIPT	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
CLDN19	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
THBD	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
KIR2DL3	RNF152	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0E1	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
KIR2DL3	FUNDC2	psi-mi:“MI:0915”(physical association)	0.560
VAMP5	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560
KIR2DL3	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
APOA2	KIR2DL3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (64): KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid), KIR2DL3 (Two-hybrid)

ESM2 similar proteins: A0A0B4J1G0, A0A0B4J1L0, A0A0G2KBC9, A1YIY0, A8MTB9, B6A8R8, C0HJX2, C0HJX3, E2RP87, H0VDZ8, P08637, P09326, P12314, P23505, P26151, P43626, P43627, P43628, P43631, P43632, P83555, P83556, Q01965, Q13291, Q14952, Q14953, Q14954, Q28942, Q2YHT5, Q61400, Q61450, Q640U3, Q68EV1, Q68SN8, Q6UX41, Q6UXE8, Q6UY09, Q6XJV4, Q6XPU4, Q7TST0

Diamond homologs: A0A0G2KBC9, A6NI73, B6A8R8, C0HJX2, C0HJX3, D3ZQX2, O75019, O75022, O75023, O76036, P0C191, P0C1X9, P24071, P43626, P43627, P43628, P43629, P43630, P43631, P43632, P59901, P83555, P83556, P97484, Q14943, Q14952, Q14953, Q14954, Q61450, Q64281, Q6GTX8, Q6ISS4, Q6PI73, Q7TQA1, Q863H2, Q8C567, Q8IYS5, Q8MJZ2, Q8MJZ7, Q8N109

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 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	8	6.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

934 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54751644:TCCA:T	acceptor_loss	1.0000
19:54751647:A:AC	acceptor_loss	1.0000
19:54751647:A:AG	acceptor_gain	1.0000
19:54751647:AG:A	acceptor_gain	1.0000
19:54751648:G:GC	acceptor_gain	1.0000
19:54751648:GG:G	acceptor_gain	1.0000
19:54751648:GGT:G	acceptor_gain	1.0000
19:54751648:GGTA:G	acceptor_gain	1.0000
19:54751648:GGTAA:G	acceptor_gain	1.0000
19:54751749:AAAAA:A	donor_gain	1.0000
19:54751750:AAAA:A	donor_gain	1.0000
19:54751751:AAA:A	donor_gain	1.0000
19:54751751:AAAGT:A	donor_loss	1.0000
19:54751752:AA:A	donor_gain	1.0000
19:54751753:AGTA:A	donor_loss	1.0000
19:54751754:G:GG	donor_gain	1.0000
19:54751755:TAAGT:T	donor_loss	1.0000
19:54738576:GTTG:G	donor_gain	0.9900
19:54738580:G:GG	donor_gain	0.9900
19:54738581:TGAGT:T	donor_loss	0.9900
19:54739609:G:T	donor_gain	0.9900
19:54739641:G:GT	donor_gain	0.9900
19:54751644:TCCAG:T	acceptor_gain	0.9900
19:54751645:CCAG:C	acceptor_gain	0.9900
19:54751646:CAG:C	acceptor_gain	0.9900
19:54751647:AGG:A	acceptor_gain	0.9900
19:54751648:G:T	acceptor_gain	0.9900
19:54752210:CTACA:C	acceptor_loss	0.9900
19:54752211:TACA:T	acceptor_loss	0.9900
19:54752212:ACAG:A	acceptor_loss	0.9900

AlphaMissense

2224 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54742252:A:C	S115R	0.961
19:54742254:T:A	S115R	0.961
19:54742254:T:G	S115R	0.961
19:54744061:A:C	S213R	0.949
19:54744063:T:A	S213R	0.949
19:54744063:T:G	S213R	0.949
19:54744016:T:A	C198S	0.947
19:54744017:G:C	C198S	0.947
19:54743869:T:A	C149S	0.945
19:54743870:G:C	C149S	0.945
19:54742081:T:C	F58L	0.944
19:54742083:C:A	F58L	0.944
19:54742083:C:G	F58L	0.944
19:54744016:T:C	C198R	0.943
19:54742207:T:A	C100S	0.936
19:54742208:G:C	C100S	0.936
19:54742054:T:A	C49S	0.933
19:54742055:G:C	C49S	0.933
19:54743870:G:A	C149Y	0.927
19:54743864:T:C	L147S	0.926
19:54743869:T:C	C149R	0.926
19:54742207:T:C	C100R	0.924
19:54742072:T:C	F55L	0.922
19:54742074:T:A	F55L	0.922
19:54742074:T:G	F55L	0.922
19:54743977:T:C	F185L	0.921
19:54743979:T:A	F185L	0.921
19:54743979:T:G	F185L	0.921
19:54743871:C:G	C149W	0.919
19:54744019:T:C	F199L	0.917

dbSNP variants (sampled 300 via entrez): RS1000137435 (19:54748332 C>A,T), RS1000769913 (19:54748914 A>C), RS1001764145 (19:54739741 CTG>C), RS1001806187 (19:54750720 A>G), RS1002444288 (19:54751056 T>C), RS1003406460 (19:54745199 A>G,T), RS1005235030 (19:54739229 G>C), RS1005260637 (19:54738196 T>C), RS1005391828 (19:54738951 T>A,C,G), RS1005445694 (19:54751911 C>T), RS1006754208 (19:54750639 T>C), RS1006857270 (19:54749687 A>T), RS1007848963 (19:54744977 T>A,C), RS1008626417 (19:54746337 G>A,C,T), RS1008969021 (19:54747210 T>A,C)

Disease associations

OMIM: gene MIM:604938 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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: yes

ChEMBL targets (1): CHEMBL3713026 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Azacitidine	decreases methylation, increases expression	2
triphenyl phosphate	affects expression	1
quercitrin	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression	1
Estradiol	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Smoke	increases expression	1
Theophylline	decreases expression	1
Valproic Acid	increases methylation	1
Particulate Matter	increases methylation	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