NCR3

Summary

NCR3 (natural cytotoxicity triggering receptor 3, HGNC:19077) is a protein-coding gene on chromosome 6p21.33, encoding Natural cytotoxicity triggering receptor 3 (O14931). Cell membrane receptor of natural killer/NK cells that is activated by binding of extracellular ligands including BAG6 and NCR3LG1.

The protein encoded by this gene is a natural cytotoxicity receptor (NCR) that may aid NK cells in the lysis of tumor cells. The encoded protein interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5’ untranslated region of this gene has been associated with mild malaria suceptibility. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 259197 — RefSeq curated summary.

At a glance

• GWAS associations: 52
• Clinical variants (ClinVar): 38 total — 1 pathogenic
• MANE Select transcript: NM_147130

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19077
Approved symbol	NCR3
Name	natural cytotoxicity triggering receptor 3
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	1C7, NKp30, CD337
Ensembl gene	ENSG00000204475
Ensembl biotype	protein_coding
OMIM	611550
Entrez	259197

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000340027, ENST00000376071, ENST00000376072, ENST00000376073, ENST00000491161, ENST00000495600, ENST00000934501, ENST00000934502

RefSeq mRNA: 3 — MANE Select: NM_147130 NM_001145466, NM_001145467, NM_147130

CCDS: CCDS34397, CCDS47401, CCDS47402

Canonical transcript exons

ENST00000340027 — 4 exons

Exon	Start	End
ENSE00001870398	31588895	31589176
ENSE00003565482	31589782	31590126
ENSE00003584144	31589526	31589633
ENSE00003841532	31592679	31593006

Expression profiles

Bgee: expression breadth ubiquitous, 118 present calls, max score 94.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.9094 / max 330.8673, expressed in 152 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72751	1.4380	122
72752	1.3677	128
72750	0.1037	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	94.36	gold quality
blood	UBERON:0000178	88.62	gold quality
lymph node	UBERON:0000029	82.89	gold quality
spleen	UBERON:0002106	82.50	gold quality
vermiform appendix	UBERON:0001154	77.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.54	gold quality
bone marrow	UBERON:0002371	67.86	gold quality
leukocyte	CL:0000738	67.56	gold quality
monocyte	CL:0000576	65.17	gold quality
apex of heart	UBERON:0002098	64.88	gold quality
mucosa of transverse colon	UBERON:0004991	64.50	gold quality
gall bladder	UBERON:0002110	62.64	gold quality
bone marrow cell	CL:0002092	62.04	silver quality
right lobe of liver	UBERON:0001114	60.95	gold quality
duodenum	UBERON:0002114	60.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	60.19	gold quality
small intestine	UBERON:0002108	59.76	gold quality
upper lobe of left lung	UBERON:0008952	59.54	gold quality
tonsil	UBERON:0002372	59.49	gold quality
right lung	UBERON:0002167	58.14	gold quality
lung	UBERON:0002048	57.76	gold quality
rectum	UBERON:0001052	57.75	gold quality
liver	UBERON:0002107	57.59	gold quality
placenta	UBERON:0001987	56.91	gold quality
right coronary artery	UBERON:0001625	54.85	gold quality
lower esophagus mucosa	UBERON:0035834	51.57	gold quality
smooth muscle tissue	UBERON:0001135	51.39	gold quality
fallopian tube	UBERON:0003889	51.11	gold quality
omental fat pad	UBERON:0010414	50.30	gold quality
adipose tissue	UBERON:0001013	50.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-122	yes	41.64
E-ANND-3	yes	7.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting NCR3, 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-532-3P	99.34	65.76	1195
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-4535	97.27	65.17	469
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 40)

• Selective cross-talk among natural cytotoxicity receptors (NKp46, NKp30 and NKp44) in human natural killer cells. (PMID:12731048)
• CD59 is physically associated with NKp46 and NKp30 and activate human nk cell-mediated cytotoxicity. (PMID:14635045)
• 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)
• NKp30 is not only a triggering molecule essential for antitumor activity but is also a surface receptor involved in natural killer cell suicide. (PMID:15728472)
• NK cell-mediated induction of dendritic cell maturation is dependent on NKp30. (PMID:15784725)
• heparan sulfate glycosaminoglycans are not ligands for NKp30, leaving open the question as to the nature of the cellular ligand for this important NK cell activation receptor (PMID:15972650)
• NKp30, among natural cytotoxicity receptors, appeared to be primarily involved in triggering NK cells upon interaction with bone marrow stromal cells (PMID:16272287)
• The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium. (PMID:16362817)
• 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)
• evidence reported of an association between mild malaria and NCR3 -412G>C polymorphism located within the promoter (PMID:17208487)
• Shown that NKp30-immunoglobulin recombinant fusion protein is Duffy binding-like proteins, natural cytotoxicity receptors are involved in naturual killer cell-Plasmodium- parasitized erythrocytes. (PMID:17436233)
• Determined expressions of NKp30 in decidual natural killer cells in patients having spontaneous abortions. (PMID:18023431)
• HLA-B-associated transcript 3 (BAT3) was released from tumor cells, bound directly to NKp30, and engaged NKp30 on NK cells. BAT3 triggered NKp30-mediated cytotoxicity and was necessary for tumor rejection in a multiple myeloma model. (PMID:18055229)
• Expression of NKp30 and NKp44 ligands was variable and did not correlate with the origin of the cell line. Expression of NKp30 and NKp44 ligand correlated with NKp30 and NKp44-mediated NK cell lysis of tumor cells, respectively (PMID:18092004)
• transcription and translation of the novel form of NKp30 can be induced by progesterone treatment (PMID:18157817)
• 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)
• NKp30 is the only functional cytotoxicity receptor expressed on a small number of freshly isolated umbilical cord blood T cells, as demonstrated by degranulation, IFN-gamma release, redirected killing, and apoptosis. (PMID:18802053)
• NKp30-mediated NK cells/dendritic cells cross talk resulting either in iDC killing or maturation was BAT3-dependent (PMID:18852879)
• Results report the identification of B7-H6, a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. (PMID:19528259)
• Myeloid-derived suppressor cell-mediated inhibition of NK cell function was dependent mainly on the NKp30 on NK cells. (PMID:19551844)
• In the presence of DC-derived cytokines such as interleukin-12, in both patients & healthy individuals, DNAM-1 can cooperate with NKp30 to induce NK cells to kill DC, release tumor necrosis factor-alpha, & promote DC maturation. (PMID:19580844)
• NKp30(high) cells are more effective in preventing infection of hepatitis C in high risk intravenous drug addicted individuals. (PMID:20812318)
• The NKp30-B7-H6 structure revealed that this NK cell activating complex is distinct from the CTLA4-B7 and PD-1-PD-L T cell inhibitory complexes in both overall organization and detailed atomic interactions that mediate binding and specificity. (PMID:21422170)
• This study provides insights into NKp30 ligand recognition and a framework for a potential family of unidentified ligands. (PMID:21444796)
• alternatively spliced isoforms affect the prognosis of gastrointestinal stromal tumors (PMID:21552268)
• 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)
• NKp30 is a triggering receptor downstream of adhesion and plays an important role in NK cell activation, degranulation and cytotoxicity. (PMID:22221078)
• NKp30 expression is significantly increased on the natural killer cells that persist at one week post-liver transplant in pediatric patients. (PMID:22360401)
• The stalk domain and the glycosylation status of the activating natural killer cell receptor NKp30 are important for ligand binding. (PMID:22807449)
• NKp30 chimeric antigen receptor-expressing T cells produce interferon (IFN)-gamma and kill B7-H6 ligand-expressing tumor cells in vivo. (PMID:22851709)
• Using a codon-optimized gene fragment, we report remarkable yields for extracellular domain of human NK cell receptor (NKp30ex) when produced on M9 minimal medium, even with low (2g/L) glucose concentration. (PMID:23059620)
• B7-H6:7D8 represents the first Ab-based molecule stimulating NKp30-mediated NK cell cytotoxicity for therapeutic purposes (PMID:23066150)
• Natural cytotoxicity receptors play a major role in the recognition by NK cells of cancer stem cells targets. (PMID:23345327)
• data describe immune escape mechanism of monoclonal gammopathy/multiple myeloma occuring via downregulation of 3 major activating NK receptors (NCR3/NKp30, NKG2D and CD244/2B4/p38) in bone marrow, that was undetectable in peripheral blood. (PMID:23360454)
• HHIP, HDAC4, NCR3 and RARB polymorphisms may have a role in impaired lung function that begins in early life (PMID:23456936)
• Cytokine stimulation combined with natural killer cell receptor engagement are required for human natural killer cell functional diversity. (PMID:23490421)
• These findings reveal that B7-H6 is not only implicated in tumor immunosurveillance but also participates in the inflammatory response in infectious conditions. (PMID:23687088)
• Findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in primary Sjogren’s syndrome. (PMID:23884468)
• we show for the first time that BAG-6(686-936) comprises a subdomain of BAG-6, which is sufficient for receptor docking and inhibition of NKp30-dependent NK cell cytotoxicity as part of a tumor immune escape mechanism (PMID:24133212)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:113337	ENSDARG00000041998
danio_rerio	si:ch211-222f23.6	ENSDARG00000042880
danio_rerio	si:ch73-22o12.1	ENSDARG00000062831
danio_rerio	pvrl2l	ENSDARG00000063390
danio_rerio	zgc:172122	ENSDARG00000079191
danio_rerio	si:ch211-214p13.3	ENSDARG00000087403
danio_rerio	si:ch211-141e20.2	ENSDARG00000093349
danio_rerio	sc:d189	ENSDARG00000102858
rattus_norvegicus	Ncr3	ENSRNOG00000000854
drosophila_melanogaster	Fas3	FBGN0000636

Paralogs (14): PVR (ENSG00000073008), CD200 (ENSG00000091972), CADM4 (ENSG00000105767), CRTAM (ENSG00000109943), NECTIN1 (ENSG00000110400), NECTIN2 (ENSG00000130202), NECTIN4 (ENSG00000143217), CD226 (ENSG00000150637), CADM3 (ENSG00000162706), SMAGP (ENSG00000170545), CADM2 (ENSG00000175161), NECTIN3 (ENSG00000177707), TIGIT (ENSG00000181847), CADM1 (ENSG00000182985)

Protein

Protein identifiers

Natural cytotoxicity triggering receptor 3 — O14931 (reviewed: O14931)

Alternative names: Activating natural killer receptor p30, Natural killer cell p30-related protein

All UniProt accessions (2): O14931, Q05D23

UniProt curated annotations — full annotation on UniProt →

Function. Cell membrane receptor of natural killer/NK cells that is activated by binding of extracellular ligands including BAG6 and NCR3LG1. Stimulates NK cells cytotoxicity toward neighboring cells producing these ligands. It controls, for instance, NK cells cytotoxicity against tumor cells. Engagement of NCR3 by BAG6 also promotes myeloid dendritic cells (DC) maturation, both through killing DCs that did not acquire a mature phenotype, and inducing the release by NK cells of TNFA and IFNG which promote DC maturation.

Subunit / interactions. Homodimer in the unliganted form. Interacts with CD3Z (PubMed:10562324, Ref.2). Interacts with and is activated by binding to NCR3LG1. Interacts with and is activated by binding to BAG6. Interacts with and is inhibited by binding to LGALS3.

Subcellular location. Cell membrane.

Tissue specificity. Selectively expressed by all resting and activated NK cells and weakly expressed in spleen.

Polymorphism. A genetic variation in NCR3 is associated with mild malaria susceptibility [MIM:609148].

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

Isoforms (6)

UniProt ID	Names	Canonical?
O14931-1	1, 1C7a	yes
O14931-2	2, 1C7c
O14931-3	3, 1C7b
O14931-4	4, 1C7e
O14931-5	5, 1C7f
O14931-6	6, 1C7d

RefSeq proteins (3): NP_001138938, NP_001138939, NP_667341* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR043226	NCR3	Family

Pfam: PF07686

UniProt features (27 total): strand 7, helix 4, splice variant 3, sequence variant 2, turn 2, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, disulfide bond 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3NOI	X-RAY DIFFRACTION	1.84
9FWW	X-RAY DIFFRACTION	1.84
3PV6	X-RAY DIFFRACTION	2.3
6YJP	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14931-F1	84.08	0.61

Antibody-complex structures (SAbDab): 1 — 9FWW

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 (1): 39–108

Glycosylation sites (2): 42, 121

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_INFLAMMATORY_RESPONSE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, 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, GNF2_IL2RB, GOBP_NATURAL_KILLER_CELL_MEDIATED_IMMUNITY, GOBP_NATURAL_KILLER_CELL_ACTIVATION, GOBP_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (8): immune response-activating cell surface receptor signaling pathway (GO:0002429), inflammatory response (GO:0006954), immune response (GO:0006955), cell recognition (GO:0008037), natural killer cell activation (GO:0030101), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), NK T cell activation (GO:0051132), immune system process (GO:0002376)

GO Molecular Function (3): identical protein binding (GO:0042802), immune receptor activity (GO:0140375), 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
immune response-activating signaling pathway	1
immune response-regulating cell surface receptor signaling pathway	1
defense response	1
immune system process	1
response to stimulus	1
cellular process	1
lymphocyte activation	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
alpha-beta T cell activation	1
biological_process	1
protein binding	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCR3	NCR3LG1	Q68D85	999
NCR3	NCR2	O95944	995
NCR3	NCR1	O76036	992
NCR3	CD247	P20963	990
NCR3	FCER1G	P30273	989
NCR3	BAG6	P46379	982
NCR3	KLRK1	P26718	970
NCR3	NECTIN2	Q92692	959
NCR3	MICB	P79525	944
NCR3	CD226	Q15762	941
NCR3	PVR	P15151	938
NCR3	FCGR3A	P08637	917
NCR3	FCGR3B	O75015	912
NCR3	NCAM1	P13591	908
NCR3	KLRC1	P26715	901

IntAct

49 interactions, top by confidence:

A	B	Type	Score
NCR3	NCR3LG1	psi-mi:“MI:0407”(direct interaction)	0.960
NCR3	NCR3LG1	psi-mi:“MI:0915”(physical association)	0.960
NCR3LG1	NCR3	psi-mi:“MI:0403”(colocalization)	0.960
NCR3LG1	NCR3	psi-mi:“MI:0915”(physical association)	0.960
NCR3LG1	NCR3	psi-mi:“MI:0407”(direct interaction)	0.960
NCR3	NCR3	psi-mi:“MI:0407”(direct interaction)	0.780
NCR3	NCR3	psi-mi:“MI:0915”(physical association)	0.780
NCR3	BAG6	psi-mi:“MI:0915”(physical association)	0.610
NCR3	BAG6	psi-mi:“MI:0407”(direct interaction)	0.610

BioGRID (119): NCR3 (Two-hybrid), NCR3 (Two-hybrid), CD59 (Affinity Capture-Western), MAN2A2 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), FUT11 (Affinity Capture-MS), HLA-C (Affinity Capture-MS), CANX (Affinity Capture-MS), LRP5 (Affinity Capture-MS), SEMA4B (Affinity Capture-MS), GALNT10 (Affinity Capture-MS), PCSK9 (Affinity Capture-MS), C1QL4 (Affinity Capture-MS), MST1R (Affinity Capture-MS)

ESM2 similar proteins: A6NKQ9, B1AWI6, I6M4H4, O14931, O35714, O46641, O54766, O70394, O95428, P08751, P0DN86, P0DN87, P17813, P19794, P21563, P43021, P51500, P51670, P60852, P61484, Q07104, Q1L6U9, Q3HRV3, Q3S2X5, Q3TYX2, Q4TUC0, Q5DQQ6, Q6AXW8, Q6NT52, Q6UWN5, Q7TPG6, Q86T13, Q86UD1, Q8BZT7, Q8CJH3, Q8IZF5, Q8K1T6, Q8MII8, Q8MJ02, Q8N386

Diamond homologs: O14931, P61483, P61484, Q8CFD9, Q8MJ02

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	16
Likely benign	18
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1803723	NM_147130.3(NCR3):c.-172G>A	Pathogenic

SpliceAI

710 predictions. Top by Δscore:

Variant	Effect	Δscore
6:31589776:TCTCA:T	donor_loss	1.0000
6:31589777:CTCAC:C	donor_loss	1.0000
6:31589778:TCACC:T	donor_loss	1.0000
6:31589779:CACCT:C	donor_loss	1.0000
6:31589780:A:T	donor_loss	1.0000
6:31589781:CC:C	donor_loss	1.0000
6:31589838:T:TA	donor_gain	1.0000
6:31589908:C:CT	acceptor_gain	1.0000
6:31592670:C:CA	donor_gain	1.0000
6:31589524:A:AC	donor_gain	0.9900
6:31589525:C:CC	donor_gain	0.9900
6:31589525:CA:C	donor_gain	0.9900
6:31589634:C:CC	acceptor_gain	0.9900
6:31589781:CCTTT:C	donor_gain	0.9900
6:31589810:C:A	donor_gain	0.9900
6:31589899:CCTGG:C	acceptor_gain	0.9900
6:31589900:C:CC	acceptor_gain	0.9900
6:31589909:A:AC	acceptor_gain	0.9900
6:31589909:A:C	acceptor_gain	0.9900
6:31589976:T:TA	donor_gain	0.9900
6:31589981:C:A	donor_gain	0.9900
6:31592667:ACGC:A	donor_gain	0.9900
6:31592668:CGCC:C	donor_gain	0.9900
6:31592673:TGTCA:T	donor_loss	0.9900
6:31592674:GTCAC:G	donor_loss	0.9900
6:31592675:TCA:T	donor_loss	0.9900
6:31592676:CACC:C	donor_loss	0.9900
6:31592677:A:AT	donor_loss	0.9900
6:31592678:CCTG:C	donor_loss	0.9900
6:31589519:TAC:T	donor_loss	0.9800

AlphaMissense

1269 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:31590047:G:C	F41L	0.993
6:31590047:G:T	F41L	0.993
6:31590049:A:G	F41L	0.993
6:31589916:A:C	F85C	0.992
6:31589915:G:C	F85L	0.987
6:31589915:G:T	F85L	0.987
6:31589917:A:G	F85L	0.987
6:31590005:C:A	W55C	0.985
6:31590005:C:G	W55C	0.985
6:31589886:A:G	I95T	0.984
6:31590007:A:G	W55R	0.982
6:31590007:A:T	W55R	0.982
6:31590048:A:C	F41C	0.982
6:31589916:A:G	F85S	0.981
6:31589848:A:G	C108R	0.976
6:31589847:C:G	C108S	0.975
6:31589848:A:T	C108S	0.975
6:31589951:G:C	F73L	0.975
6:31589951:G:T	F73L	0.975
6:31589953:A:G	F73L	0.975
6:31590048:A:G	F41S	0.975
6:31589572:G:C	S150R	0.973
6:31589572:G:T	S150R	0.973
6:31589574:T:G	S150R	0.973
6:31589952:A:C	F73C	0.973
6:31590018:C:T	G51D	0.973
6:31589847:C:T	C108Y	0.972
6:31589548:G:C	S158R	0.965
6:31589548:G:T	S158R	0.965
6:31589550:T:G	S158R	0.965

dbSNP variants (sampled 300 via entrez): RS1000228388 (6:31588957 A>G), RS1000229937 (6:31591538 G>A,C,T), RS1000578864 (6:31591874 G>A), RS1001856417 (6:31593251 C>T), RS1001936166 (6:31594944 T>C), RS1002617222 (6:31589451 C>T), RS1003522619 (6:31594826 G>T), RS1003952132 (6:31591830 C>T), RS1004178591 (6:31594168 G>A,C), RS1004294625 (6:31594468 A>G), RS1004888302 (6:31594857 T>A), RS1006321912 (6:31589371 T>A), RS1006990572 (6:31592282 G>A), RS1007043297 (6:31591980 T>C), RS1007721715 (6:31592324 A>G)

Disease associations

OMIM: gene MIM:611550 | disease phenotypes: MIM:609148

GenCC curated gene-disease

Mondo (1): malaria, mild, susceptibility to (MONDO:0012202)

Orphanet (0):

HPO phenotypes

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

GWAS associations

52 associations (top):

Study	Trait	p-value
GCST000299_1	Weight	2.000000e-08
GCST001248_12	Pulmonary function	2.000000e-10
GCST001251_8	Pulmonary function	1.000000e-06
GCST001784_3	Pulmonary function (smoking interaction)	8.000000e-08
GCST002876_4	Type 1 diabetes and autoimmune thyroid diseases	2.000000e-23
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004183_12	Lung function (FEV1)	2.000000e-06
GCST004185_50	Lung function (FEV1/FVC)	4.000000e-09
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST005038_108	Allergic disease (asthma, hay fever or eczema)	9.000000e-16
GCST005542_1	Sarcoidosis (non-Lofgren’s syndrome without extrapulmonary manifestations)	7.000000e-06
GCST005790_61	Rosacea symptom severity	3.000000e-12
GCST006575_36	Takayasu arteritis	1.000000e-09
GCST008916_111	Asthma	2.000000e-14
GCST008916_114	Asthma	1.000000e-09
GCST008916_30	Asthma	1.000000e-09
GCST008917_2	Asthma (childhood onset)	4.000000e-07
GCST008921_1	Asthma and major depressive disorder	2.000000e-16
GCST010477_7	Hypertension	5.000000e-07
GCST010725_43	Malaria	5.000000e-07

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0009180	rosacea severity measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1052248	LST1, NCR3		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — CD molecules

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
mirdametinib	decreases reaction, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Catechin	affects cotreatment, decreases expression	1
Diuron	decreases expression	1
Toxic Actions	decreases expression	1
Mycophenolic Acid	decreases expression	1
Tretinoin	decreases expression	1
Zinc	increases expression	1
Tacrolimus	increases expression	1
Cyclosporine	increases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7BP	Abeomics CHO-K1 NKp30	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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