NCR1

Summary

NCR1 (natural cytotoxicity triggering receptor 1, HGNC:6731) is a protein-coding gene on chromosome 19q13.42, encoding Natural cytotoxicity triggering receptor 1 (O76036). Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis.

Predicted to be involved in immune response-regulating signaling pathway. Predicted to act upstream of or within defense response to virus and detection of virus. Predicted to be located in cell surface. Predicted to be part of SWI/SNF complex. Predicted to be active in plasma membrane. Biomarker of acquired immunodeficiency syndrome; anogenital venereal wart; hepatitis C; and lymphoproliferative syndrome.

Source: NCBI Gene 9437 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 215 total — 7 pathogenic, 5 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_004829

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6731
Approved symbol	NCR1
Name	natural cytotoxicity triggering receptor 1
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	NK-p46, NKP46, CD335
Ensembl gene	ENSG00000189430
Ensembl biotype	protein_coding
OMIM	604530
Entrez	9437

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000291890, ENST00000338835, ENST00000350790, ENST00000357397, ENST00000594765, ENST00000598576, ENST00000601137, ENST00000601903

RefSeq mRNA: 5 — MANE Select: NM_004829 NM_001145457, NM_001145458, NM_001242356, NM_001242357, NM_004829

CCDS: CCDS12911, CCDS46181, CCDS46182, CCDS56103

Canonical transcript exons

ENST00000291890 — 7 exons

Exon	Start	End
ENSE00001052306	54912168	54912218
ENSE00001052311	54906299	54906334
ENSE00001052312	54910018	54910065
ENSE00001312058	54909245	54909523
ENSE00001380161	54906148	54906221
ENSE00003141578	54912690	54913073
ENSE00003466174	54906523	54906807

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 86.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6881 / max 272.2753, expressed in 182 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177567	1.4578	168
177565	0.1228	67
177566	0.0585	34
177568	0.0489	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	86.52	gold quality
blood	UBERON:0000178	84.26	gold quality
spleen	UBERON:0002106	72.09	gold quality
bone marrow cell	CL:0002092	69.71	silver quality
bone marrow	UBERON:0002371	68.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.99	gold quality
leukocyte	CL:0000738	65.58	gold quality
monocyte	CL:0000576	63.53	gold quality
placenta	UBERON:0001987	61.15	gold quality
liver	UBERON:0002107	60.28	gold quality
right lobe of liver	UBERON:0001114	58.90	gold quality
lymph node	UBERON:0000029	58.74	gold quality
right lung	UBERON:0002167	57.74	gold quality
lung	UBERON:0002048	57.54	gold quality
upper lobe of left lung	UBERON:0008952	57.29	gold quality
colonic epithelium	UBERON:0000397	57.01	silver quality
duodenum	UBERON:0002114	55.49	gold quality
vermiform appendix	UBERON:0001154	55.13	gold quality
tonsil	UBERON:0002372	53.96	gold quality
gall bladder	UBERON:0002110	52.43	gold quality
rectum	UBERON:0001052	52.34	gold quality
endometrium	UBERON:0001295	51.19	gold quality
smooth muscle tissue	UBERON:0001135	49.79	gold quality
omental fat pad	UBERON:0010414	47.12	gold quality
mucosa of transverse colon	UBERON:0004991	45.94	gold quality
fallopian tube	UBERON:0003889	45.66	gold quality
muscle tissue	UBERON:0002385	45.65	gold quality
apex of heart	UBERON:0002098	44.85	silver quality
right coronary artery	UBERON:0001625	44.62	gold quality
lower esophagus mucosa	UBERON:0035834	44.58	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	453.22
E-ANND-3	yes	6.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A, RUNX3

miRNA regulators (miRDB)

5 targeting NCR1, 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-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-301A-5P	96.88	68.07	931
HSA-MIR-301B-5P	96.88	67.75	946

Literature-anchored findings (GeneRIF, showing 40)

• The NKp46 receptor participates in NK cell-mediated lysis of cells infected with the intracellular pathogen Mycobacterium tuberculosis, an activity that is reduced in tuberculosis patients compared with findings in healthy donors. (PMID:11907104)
• Selective cross-talk among natural cytotoxicity receptors (NKp46, NKp30 and NKp44) in human natural killer cells. (PMID:12731048)
• crystal structure of the human natural killer (NK) cell activating receptor NKp46 (PMID:12960161)
• NKp46 interacts with both viral hemagglutinins and the unknown tumor ligands via different mechanisms. (PMID:14504081)
• CD59 is physically associated with NKp46 and NKp30 and activate human nk cell-mediated cytotoxicity. (PMID:14635045)
• natural cytotoxicity receptor (NCR) and NK receptor member D of the lectin-like receptor family (NKG2D) were the key NK activating receptors for bone marrow-derived myeloma cell recognition (PMID:15328155)
• NKG2D, NKp30, NKp44, and NKp46 acitvation affected by ligand-negative phenotype in bone marrow-derived progenitor cells, acquisition of cell-surface ligands during myeloid differentiation, defective expression of ligands on malignant transformation (PMID:15657183)
• NKp46 is not only a triggering molecule essential for antitumor activity but is also a surface receptor involved in natural killer cell suicide. (PMID:15728472)
• Results examine residues in NKp46 that may be involved in heparan sulfate binding on tumor cells. (PMID:16262248)
• defect in cytotoxic effector function is associated with a reduced surface expression of activating NK receptors (NKp30, NKp46, and NKG2D) on CD56(dim) NK cells compared with uninfected newborns. (PMID:16690951)
• Vimentin is involved in binding of NKp46 to M. tuberculosis H37Ra-infected mononuclear phagocytes. (PMID:17056548)
• The natural cytotoxicity receptor NKp46 was required for the killing of all myeloma cell lines analyzed. (PMID:17875681)
• There is a correlation between the malignant potential of the lesion and the expression of NKp46 ligands in the reticular dermis. (PMID:17972960)
• Determined expressions of NKp46 in decidual natural killer cells in patients having spontaneous abortions. (PMID:18023431)
• in NK cells cultured with IL-15, we observed an up-regulation of the activating receptors NKG2D, NKp30, and NKp46, associated with an increase in anti-tumor lytic activity. (PMID:18275895)
• differential, controlled role of NKp46- and NKp30-activating receptors expressed by uterine dNK that could be critical for the outcome of pregnancy (PMID:18713971)
• Brain-infiltrating natural killer (NK) cells might restrict innate and adaptive immune responses via elimination of resting microglia; this cell killing is dependent on cell contact, NKp46, and NKG2D. (PMID:18941207)
• On co-culture with some melanomas, activated CD4(+) T cells promoted NKG2D- and NKp46-dependent IFN-gamma secretion by NK cells, probably owing to the capture of NKG2D and NKp46 ligands from the tumour-cell surface (trogocytosis). (PMID:19498463)
• NKp46 is essential for the development of type 1 diabetes (PMID:20023661)
• The balance of NKp44(+)/NKp46(+) NK cells is disrupted in intestinal mucosa of patients with Crohn’s disease. (PMID:20638936)
• Data show that only NKp46 appeared involved in the NK response. (PMID:21030563)
• peripheral blood malignant CD4(+) T lymphocytes from patients with Sezary syndrome, an aggressive form of cutaneous T-cell lymphoma, express NKp46 at their cell surface (PMID:21191411)
• Data show that an increase in 2B4-expressing NK cells and a decrease in NKp46(+) NK cells occurred following intramuscular influenza vaccination. (PMID:21214542)
• NKp46 interacts with heparin and heparan sulfate, highly sulfated glycans, and multimeric alpha2,3-NeuAc-containing N-glycan; these glycans interact mainly with basic amino acids in NKp46. (PMID:21329668)
• NKp46 identifies a functionally distinct NKT subset in that appears to be directly susceptible to leukemic transformation when IL-15 is overexpressed. (PMID:21364281)
• we investigate whether NKp46 is involved in the killing of human beta cells (PMID:21849674)
• a precise analysis of clinical data showed a correlation between decreased NCR expression and poor prognosis factors such as low haemoglobin level, high (>30x10(9) per litre) lymphocyte count or elevated C-reactive protein (PMID:22044312)
• decreased expression is associated with altered NK-cell function in pediatric transplant patients with PTLD (PMID:22105417)
• important role in inhibition of liver fibrosis (PMID:22198715)
• This study demonistrated that NCR1 expression on astrocytes in MS tissue. (PMID:22212381)
• findings show that NK cells can significantly accelerate neutrophil apoptosis, and that this process is dependent on cell-cell contact and mediated by the activating NK cell receptor NKp46 and the Fas pathway (PMID:22231698)
• Role of runt-related transcription factor 3 (RUNX3) in transcription regulation of natural cytotoxicity receptor 1 (NCR1/NKp46), an activating natural killer (NK) cell receptor. (PMID:22253448)
• NKp46 levels remain stable on the natural killer cells that persist at one week post-liver transplant in pediatric patients. (PMID:22360401)
• Race and gender related variation found in NKp46 receptor expression with differential anti-hepatitis C virus immunity. (PMID:22505144)
• NKp46 expression of hepatitis C virus replication controls the modulation of liver fibrosis. (PMID:22532190)
• We suggest that NKp46 dimerization contributes to NKp46-mediated lysis by NK cells. (PMID:22615207)
• expressed in all investigated cases of transformed mycosis fungoides (PMID:22621189)
• IL-15+IL-12 has an immunomodulatory effect on NK cell subsets from HIV-infected individuals viz down-regulation of iNKRs, elevation of activatory receptors NKp46 and NKG2D, and induction of coreceptor NKp80. (PMID:22715368)
• involved in cytokine production of CD56+ NK cells in the uterine endometrium (PMID:23311919)
• PLS3, Twist, KIR3DL2 and NKp46 gene expression can model efficient molecular Sezary syndrome diagnosis. (PMID:23429988)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ncr1	ENSMUSG00000062524
rattus_norvegicus	Ncr1	ENSRNOG00000027855

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), LILRB3 (ENSG00000204577), KIR2DS4 (ENSG00000221957), LILRA4 (ENSG00000239961), LILRA2 (ENSG00000239998), KIR3DL2 (ENSG00000240403), KIR3DL3 (ENSG00000242019), KIR2DL3 (ENSG00000243772), LILRA6 (ENSG00000244482), TARM1 (ENSG00000248385)

Protein

Protein identifiers

Natural cytotoxicity triggering receptor 1 — O76036 (reviewed: O76036)

Alternative names: Lymphocyte antigen 94 homolog, NK cell-activating receptor, Natural killer cell p46-related protein

All UniProt accessions (5): A0A0A0MQZ0, A0A0A0MR94, A0A0A0MTU0, M0QYD1, O76036

UniProt curated annotations — full annotation on UniProt →

Function. Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis.

Subunit / interactions. Interacts with CD247 and FCER1G.

Subcellular location. Cell membrane.

Tissue specificity. Selectively expressed by both resting and activated NK cells.

Post-translational modifications. N-glycosylated. O-glycosylated.

Similarity. Belongs to the natural cytotoxicity receptor (NCR) family.

Isoforms (6)

UniProt ID	Names	Canonical?
O76036-1	1	yes
O76036-2	2, b
O76036-3	3, c
O76036-4	4, d
O76036-5	5
O76036-6	6

RefSeq proteins (5): NP_001138929, NP_001138930, NP_001229285, NP_001229286, NP_004820* (*=MANE)

Domains & families (InterPro)

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

UniProt features (37 total): strand 19, splice variant 4, sequence variant 2, topological domain 2, helix 2, domain 2, disulfide bond 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9H8R	X-RAY DIFFRACTION	1.75
1OLL	X-RAY DIFFRACTION	1.93
1P6F	X-RAY DIFFRACTION	2.2
6IAP	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76036-F1	84.11	0.66

Antibody-complex structures (SAbDab): 1 — 6IAP

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): 49–98, 144–190

Glycosylation sites (1): 216

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: 118 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_NATURAL_KILLER_CELL_MEDIATED_IMMUNITY, GOBP_NATURAL_KILLER_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_IMMUNE_EFFECTOR_PROCESS

GO Biological Process (5): immune response-regulating signaling pathway (GO:0002764), cellular defense response (GO:0006968), signal transduction (GO:0007165), natural killer cell activation (GO:0030101), regulation of natural killer cell mediated cytotoxicity (GO:0042269)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), SWI/SNF complex (GO:0016514), 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
signal transduction	1
regulation of immune response	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lymphocyte activation	1
regulation of leukocyte mediated cytotoxicity	1
regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
binding	1
membrane	1
cell periphery	1
SWI/SNF superfamily-type complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCR1	FCER1G	P30273	995
NCR1	NCR2	O95944	995
NCR1	CD247	P20963	995
NCR1	NCR3	O14931	992
NCR1	FCGR3A	P08637	985
NCR1	KLRK1	P26718	983
NCR1	TYROBP	O43914	973
NCR1	CFP	P27918	958
NCR1	NCR3LG1	Q68D85	958
NCR1	MICB	P79525	955
NCR1	FCGR3B	O75015	955
NCR1	CD226	Q15762	925
NCR1	ULBP1	Q9BZM6	904
NCR1	NCAM1	P13591	901
NCR1	PRF1	P14222	880

IntAct

16 interactions, top by confidence:

A	B	Type	Score
VIM	NCR1	psi-mi:“MI:0915”(physical association)	0.610
VIM	NCR1	psi-mi:“MI:0407”(direct interaction)	0.610
CFP	NCR1	psi-mi:“MI:0407”(direct interaction)	0.540
CFP	NCR1	psi-mi:“MI:0915”(physical association)	0.540
NCR1	CFP	psi-mi:“MI:0915”(physical association)	0.540
CFP	NCR1	psi-mi:“MI:0407”(direct interaction)	0.440
NCR1	HA	psi-mi:“MI:0407”(direct interaction)	0.440
NCR1	CD3E	psi-mi:“MI:0915”(physical association)	0.400
NCR1	FCER1G	psi-mi:“MI:0915”(physical association)	0.400
Cfp	NCR1	psi-mi:“MI:0915”(physical association)	0.400
NCR1	OSER1	psi-mi:“MI:0914”(association)	0.350
NCR1	ORC4	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): NCR1 (Reconstituted Complex), NCR1 (Reconstituted Complex), NCR1 (Affinity Capture-MS), NCR1 (Two-hybrid), NCR1 (Two-hybrid), NCR1 (Two-hybrid), TMEM229B (Two-hybrid), CD247 (Affinity Capture-Western), CD59 (Affinity Capture-Western), GSTK1 (Affinity Capture-MS), OSER1 (Affinity Capture-MS), SEC63 (Affinity Capture-MS), TNFSF9 (Affinity Capture-MS), ORC4 (Affinity Capture-MS), ANKRD13A (Affinity Capture-MS)

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

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

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	5
Uncertain significance	108
Likely benign	18
Benign	5

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1585	NM_001127255.2(NLRP7):c.2471+1G>A	Pathogenic
1591	NM_001127255.2(NLRP7):c.2078G>A (p.Arg693Gln)	Pathogenic
3235890	NM_001127255.2(NLRP7):c.2585G>A (p.Gly862Glu)	Pathogenic
41407	NM_001127255.2(NLRP7):c.2030delT (p.Leu677Profs)	Pathogenic
4686607	NM_001127255.2(NLRP7):c.2227G>A (p.Glu743Lys)	Pathogenic
97748	NM_001127255.2(NLRP7):c.2161C>T (p.Arg721Trp)	Pathogenic
97750	NM_001127255.2(NLRP7):c.2248C>G (p.Leu750Val)	Pathogenic
1588	NM_001127255.2(NLRP7):c.2738A>G (p.Asn913Ser)	Likely pathogenic
2635805	NM_001127255.2(NLRP7):c.2808dup (p.Arg937fs)	Likely pathogenic
3376766	NM_001127255.2(NLRP7):c.2177C>T (p.Ala726Val)	Likely pathogenic
3382290	NM_001127255.2(NLRP7):c.2218_2224del (p.Gly740fs)	Likely pathogenic
830330	NM_001127255.2(NLRP7):c.2320_2321insT (p.Thr774Ilefs)	Likely pathogenic

SpliceAI

911 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54910015:CAGG:C	acceptor_loss	1.0000
19:54910016:A:AG	acceptor_gain	1.0000
19:54910016:AGG:A	acceptor_loss	1.0000
19:54910016:AGGC:A	acceptor_gain	1.0000
19:54910017:G:GA	acceptor_gain	1.0000
19:54910017:GGC:G	acceptor_gain	1.0000
19:54910017:GGCG:G	acceptor_gain	1.0000
19:54910017:GGCGA:G	acceptor_gain	1.0000
19:54906804:ACAG:A	donor_gain	0.9900
19:54909269:C:A	acceptor_gain	0.9900
19:54909279:T:TA	acceptor_gain	0.9900
19:54909280:G:A	acceptor_gain	0.9900
19:54909519:CACAG:C	donor_loss	0.9900
19:54909520:ACAGG:A	donor_loss	0.9900
19:54909523:GGTGA:G	donor_loss	0.9900
19:54909524:GTG:G	donor_loss	0.9900
19:54909525:T:G	donor_loss	0.9900
19:54910004:A:AG	acceptor_gain	0.9900
19:54910005:T:G	acceptor_gain	0.9900
19:54910016:AG:A	acceptor_gain	0.9900
19:54910017:GG:G	acceptor_gain	0.9900
19:54910066:G:A	donor_loss	0.9900
19:54910067:T:A	donor_loss	0.9900
19:54906218:GTCG:G	donor_gain	0.9800
19:54906222:G:A	donor_loss	0.9800
19:54906222:G:GG	donor_gain	0.9800
19:54906223:TGA:T	donor_loss	0.9800
19:54906224:GAGTT:G	donor_loss	0.9800
19:54906226:G:C	donor_loss	0.9800
19:54906803:AACAG:A	donor_loss	0.9800

AlphaMissense

1976 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54909457:T:A	C190S	0.989
19:54909458:G:C	C190S	0.989
19:54909319:T:A	C144S	0.987
19:54909320:G:C	C144S	0.987
19:54909346:T:C	F153L	0.984
19:54909348:C:A	F153L	0.984
19:54909348:C:G	F153L	0.984
19:54909451:T:G	Y188D	0.984
19:54909496:A:C	S203R	0.984
19:54909498:T:A	S203R	0.984
19:54909498:T:G	S203R	0.984
19:54906738:T:G	Y96D	0.982
19:54909321:C:G	C144W	0.982
19:54909320:G:A	C144Y	0.981
19:54909413:T:G	F175C	0.981
19:54909457:T:C	C190R	0.981
19:54909459:T:G	C190W	0.979
19:54909412:T:C	F175L	0.976
19:54909414:C:A	F175L	0.976
19:54909414:C:G	F175L	0.976
19:54909455:G:C	R189P	0.976
19:54909460:T:C	F191L	0.976
19:54909462:T:A	F191L	0.976
19:54909462:T:G	F191L	0.976
19:54906597:T:A	C49S	0.973
19:54906598:G:C	C49S	0.973
19:54909319:T:C	C144R	0.973
19:54906744:T:A	C98S	0.972
19:54906745:G:C	C98S	0.972
19:54909488:C:T	S200F	0.972

dbSNP variants (sampled 300 via entrez): RS1000090386 (19:54926162 G>A), RS1000139165 (19:54922058 G>A), RS1000149676 (19:54904821 C>T), RS1000240589 (19:54907050 G>A), RS1000312623 (19:54912402 G>C), RS1000502368 (19:54905222 C>G), RS1000528233 (19:54926404 A>G), RS1000542413 (19:54929768 G>A), RS1000619802 (19:54907220 A>G), RS1000653941 (19:54927033 T>A), RS1000695300 (19:54916520 T>C), RS1000822445 (19:54903023 G>A), RS1000854071 (19:54917434 C>G), RS1000907100 (19:54901235 A>G), RS1000942368 (19:54920768 G>A,C)

Disease associations

OMIM: gene MIM:604530 | disease phenotypes: MIM:231090, MIM:621471

GenCC curated gene-disease

Mondo (3): hydatidiform mole, recurrent, 1 (MONDO:0009273), hydatidiform mole (MONDO:0006248), oocyte/zygote/embryo maturation arrest 25 (MONDO:0980964)

Orphanet (2): Complete hydatidiform mole (Orphanet:254688), Hydatidiform mole (Orphanet:99927)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_332	Blood protein levels	1.000000e-17
GCST009391_67	Metabolite levels	9.000000e-06
GCST90002394_567	Monocyte percentage of white cells	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010352	diacylglycerol 34:1 measurement
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006828	Hydatidiform Mole	C04.557.465.955.416.812; C04.850.908.416.750; C12.050.703.720.949.416.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066290 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	decreases expression, increases methylation	2
Benzo(a)pyrene	increases expression, affects methylation	2
GSK-J4	decreases expression	1
bisphenol F	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression, decreases reaction	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Bortezomib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects methylation, increases abundance	1
Cadmium	decreases expression, increases abundance	1
Catechin	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, decreases expression	1
Mycophenolic Acid	decreases expression	1
Nickel	affects expression, decreases reaction	1
Ozone	affects methylation, increases abundance	1
Tretinoin	decreases expression	1
Valproic Acid	affects cotreatment, decreases expression	1
Asbestos, Serpentine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5510492	Binding	Binding affinity to NKp46 (unknown origin) assessed as dissociation constant by fluorescence polarization assay	Discovery of Glutamate Carboxypeptidase III Ligands to Compete the Uptake of [177Lu]Lu-PSMA-617 in Healthy Organs. — J Med Chem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8LA	Abcam HCT 116 NCR1 KO	Cancer cell line	Male
CVCL_B9NG	Abcam A-549 NCR1 KO	Cancer cell line	Male
CVCL_D2GL	Abcam MCF-7 NCR1 KO	Cancer cell line	Female
CVCL_D7BQ	Abeomics CHO-K1 NKp46	Spontaneously immortalized cell line	Female
CVCL_E6RB	Genomeditech CHO-K1 H_NCR1(NKp46)	Spontaneously immortalized cell line	Female
CVCL_E6UP	Genomeditech HEK-293 H_NCR1(NKp46)	Transformed cell line	Female
CVCL_E6VW	Genomeditech Jurkat H_NCR1(NKp46) Reporter	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01630954	PHASE4	UNKNOWN	A Comparison of Single Versus Double Evacuation for Treatment of Hydatidiform Mole
NCT00003702	PHASE3	COMPLETED	Methotrexate Compared With Dactinomycin in Treating Patients With Gestational Trophoblastic Neoplasia
NCT01535053	PHASE3	COMPLETED	Dactinomycin or Methotrexate in Treating Patients With Low-Risk Gestational Trophoblastic Neoplasia
NCT01984099	PHASE3	COMPLETED	RCT on the Efficacy of Methotrexate for the Prevention of GTD
NCT04756713	PHASE3	UNKNOWN	Second Uterine Evacuation for Low-risk Gestational Trophoblastic Neoplasia
NCT00190918	PHASE2	COMPLETED	A Trial for Patients With Gestational Trophoblastic Disease
NCT01008501	Not specified	ACTIVE_NOT_RECRUITING	Study of the Genetic and Epigenetic Causes of Recurrent Hydatidiform Moles
NCT02892877	Not specified	RECRUITING	The French National Reference Centre of GTD
NCT03785574	Not specified	RECRUITING	Study of Different Therapeutic Strategies in Hydatidiform Mole With Lung Nodule
NCT05516810	Not specified	ACTIVE_NOT_RECRUITING	The Accuracy of Ultrasound Diagnosis of Hydatidiform Moles
NCT05637892	Not specified	NOT_YET_RECRUITING	A Cohort Study of Hydatidiform Mole
NCT07202728	Not specified	RECRUITING	A Multi-center Cohort Study of Hydatidiform Mole in China (CN-HM-01)