CLEC2D

Summary

CLEC2D (C-type lectin domain family 2 member D, HGNC:14351) is a protein-coding gene on chromosome 12p13.31, encoding C-type lectin domain family 2 member D (Q9UHP7). Receptor for KLRB1 that protects target cells against natural killer cell-mediated lysis.

This gene encodes a member of the natural killer cell receptor C-type lectin family. The encoded protein inhibits osteoclast formation and contains a transmembrane domain near the N-terminus as well as the C-type lectin-like extracellular domain. Several alternatively spliced transcript variants have been identified for this gene.

Source: NCBI Gene 29121 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_013269

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14351
Approved symbol	CLEC2D
Name	C-type lectin domain family 2 member D
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	LLT1, CLAX, OCIL
Ensembl gene	ENSG00000069493
Ensembl biotype	protein_coding
OMIM	605659
Entrez	29121

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261339, ENST00000261340, ENST00000290855, ENST00000325960, ENST00000430909, ENST00000444971, ENST00000460309, ENST00000466035, ENST00000476198, ENST00000479877, ENST00000487752, ENST00000492359, ENST00000536355, ENST00000543300, ENST00000544322, ENST00000545918

RefSeq mRNA: 5 — MANE Select: NM_013269 NM_001004419, NM_001197317, NM_001197318, NM_001197319, NM_013269

CCDS: CCDS31741, CCDS55800, CCDS55801, CCDS55802, CCDS8602

Canonical transcript exons

ENST00000290855 — 5 exons

Exon	Start	End
ENSE00001490459	9694760	9699553
ENSE00001749608	9669713	9669795
ENSE00003491652	9680923	9681033
ENSE00003507964	9687902	9688086
ENSE00003517512	9692828	9692931

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 97.03.

FANTOM5 (CAGE): breadth broad, TPM avg 11.4763 / max 586.1712, expressed in 416 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124077	7.0490	239
124078	2.1317	179
124084	1.0009	255
124079	0.6364	137
124080	0.2479	62
124083	0.2268	57
124076	0.1106	39
124082	0.0729	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.03	gold quality
calcaneal tendon	UBERON:0003701	92.50	gold quality
spleen	UBERON:0002106	92.12	gold quality
lymph node	UBERON:0000029	91.21	gold quality
blood	UBERON:0000178	89.24	gold quality
vermiform appendix	UBERON:0001154	89.12	gold quality
right uterine tube	UBERON:0001302	88.86	gold quality
leukocyte	CL:0000738	88.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.02	gold quality
colonic epithelium	UBERON:0000397	87.98	gold quality
monocyte	CL:0000576	87.71	gold quality
mononuclear cell	CL:0000842	87.55	gold quality
bone marrow cell	CL:0002092	86.93	gold quality
tibial nerve	UBERON:0001323	86.76	gold quality
mucosa of stomach	UBERON:0001199	86.64	gold quality
right testis	UBERON:0004534	86.34	gold quality
left testis	UBERON:0004533	85.80	gold quality
minor salivary gland	UBERON:0001830	84.70	gold quality
ventricular zone	UBERON:0003053	84.50	gold quality
tonsil	UBERON:0002372	84.44	gold quality
adrenal tissue	UBERON:0018303	84.38	gold quality
right lung	UBERON:0002167	83.99	gold quality
right ovary	UBERON:0002118	83.83	gold quality
small intestine	UBERON:0002108	83.58	gold quality
apex of heart	UBERON:0002098	83.51	gold quality
upper lobe of left lung	UBERON:0008952	83.27	gold quality
bone marrow	UBERON:0002371	83.26	gold quality
omental fat pad	UBERON:0010414	83.18	gold quality
left ovary	UBERON:0002119	83.14	gold quality
peritoneum	UBERON:0002358	83.10	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	3142.91
E-MTAB-8142	yes	734.74
E-CURD-79	yes	706.65
E-CURD-112	yes	46.57
E-MTAB-6678	yes	42.03
E-HCAD-1	yes	38.73
E-CURD-122	yes	35.70
E-CURD-88	yes	33.39
E-CURD-46	yes	31.64
E-GEOD-135922	yes	25.14
E-MTAB-8410	yes	20.77
E-HCAD-10	yes	15.70
E-MTAB-9067	yes	14.37
E-GEOD-130148	yes	6.12
E-MTAB-9801	yes	6.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP7

miRNA regulators (miRDB)

157 targeting CLEC2D, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4725-3P	99.96	69.53	2520

Literature-anchored findings (GeneRIF, showing 25)

• LLT1 induces Interferon Type II production by natural killer cells. (PMID:15104121)
• Data show that osteoclast inhibitory lectin (OCIL) binds a range of physiologically important glycosaminoglycans, and this property may modulate OCIL actions upon other cells [OCIL]. (PMID:15123656)
• Engagement of CD161 on NK cells with LLT1 expressed on target cells inhibited NK cell-mediated cytotoxicity and IFN-gamma secretion. LLT1/CD161 interaction in the presence of a TCR signal enhanced IFN-gamma production by T cells (PMID:16339512)
• LLT1 on target cells can inhibit NK cytotoxicity via interactions with CD161. LLT1 activates NFAT-GFP reporter cells expressing a CD3zeta-CD161 chimeric receptor; reciprocally, reporter cells with a CD3zeta-LLT1 chimeric receptor are stimulated by CD161 (PMID:16339513)
• Expression of LLT1 on activated dendritic cells and B cells suggests that it might regulate the cross-talk between NK cells and APCs (PMID:18453569)
• Women with a lysine (GG genotype) at position 19 of the OCIL protein displayed lower bone mineral density at femoral neck and at lumbar spine sites than women having an asparagine residue. (PMID:18465072)
• LLT1 used Src-PTK, p38 and ERK signalling pathways, but not PKC, PI3K or calcineurin pathways, to increase production of IFN-gamma by human natural killer cells. (PMID:20415786)
• Data show that only CLEC2D isoform 1 (LLT1) is expressed on the cell surface. (PMID:20843815)
• Molecular basis for LLT1 protein recognition by human CD161 protein (NKRP1A/KLRB1). (PMID:21572041)
• LLT1 and CD161 have roles in modulating immune responses to pathogens; and interferon-gamma contributes to modulate immune responses (PMID:21930700)
• One polymorphism in LLT1 was found to be associated with our Crohn’s Disease population (P<0.034).Our Ulcerative Colitis cohort was not associated with the variation in LLT1 (P=0.33) (PMID:22664939)
• The hexamer of glycosylated LLT1 consists of three classical dimers. The hexameric packing may indicate a possible mode of interaction of C-type lectin-like proteins in the glycosylated form. (PMID:25760607)
• In RA joints, LLT1 is expressed by cells of the monocyte/macrophage lineage. (PMID:26147876)
• these data suggest that LLT1-CD161 interactions play a novel and important role in B cell maturation within the Germinal center in humans. (PMID:26829983)
• Blocking LLT1-NKRP1A interaction will make prostate cancer cells susceptible to killing by NK cells, suggesting a therapeutic option for treatment of prostate cancer. (PMID:27626681)
• These results show that susceptibility of normal articular chondrocytes to lysis by NK cells is modulated by NKR-P1A/LLT1 interactions. Thus, NKR-P1A/LLT1 interaction might provide some novel target for therapeutic interventions in the course of pathological cartilage injury. (PMID:29212911)
• LLT1 strong expression was a significant risk factor for nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma (cSCC) and for cSCC specific mortality. Strong LLT1 expression is an independent predictor of nodal metastasis and poor disease-specific survival and it might be helpful for risk stratification of patients with cSCC. (PMID:30955082)
• REVIEW: Biological and Clinical Significance of Human NKRP1A/LLT1 Receptor/Ligand Interactions (PMID:31002602)
• The authors identify Clec2d as a sensor for cell death through histone recognition and show that such interaction in macrophages shuttles histone-DNA complexes into endosomes to stimulate toll-like receptors. The consequent inflammation amplifies collateral tissue damage in a liver injury model. (PMID:31859049)
• Docetaxel suppresses immunotherapy efficacy of natural killer cells toward castration-resistant prostate cancer cells via altering androgen receptor-lectin-like transcript 1 signals. (PMID:32449811)
• Role of LLT1 and PCNA as Natural Killer Cell Immune Evasion Strategies of HCT 116 Cells. (PMID:33288556)
• LLT1-CD161 Interaction in Cancer: Promises and Challenges. (PMID:35185935)
• SARS-CoV-2 infection impairs NK cell functions via activation of the LLT1-CD161 axis. (PMID:37287972)
• Immune checkpoint CD161/LLT1-associated immunological landscape and diagnostic value in oral squamous cell carcinoma. (PMID:38502058)
• Lectin-like Transcript-1 (LLT1) Expression in Oral Squamous Cell Carcinomas: Prognostic Significance and Relationship with the Tumor Immune Microenvironment. (PMID:38673902)

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-193e13.5	ENSDARG00000052656
danio_rerio		ENSDARG00000074732
danio_rerio	si:dkey-26c10.5	ENSDARG00000088023
danio_rerio	si:ch211-170d8.8	ENSDARG00000090945
mus_musculus	Clec2g	ENSMUSG00000000248
mus_musculus	Clec2e	ENSMUSG00000030155
mus_musculus	Clec2d	ENSMUSG00000030157
mus_musculus	Clec2h	ENSMUSG00000030364
mus_musculus	Clec2i	ENSMUSG00000030365
rattus_norvegicus	Clec2d2l3	ENSRNOG00000030522
rattus_norvegicus	Clec2d2l1	ENSRNOG00000037076
rattus_norvegicus	Clec2d	ENSRNOG00000048726
rattus_norvegicus	Clec2e	ENSRNOG00000052128
rattus_norvegicus	Clec2d2	ENSRNOG00000059890
rattus_norvegicus	Clec2h	ENSRNOG00000061757
rattus_norvegicus	Clec2d2l2	ENSRNOG00000069744
rattus_norvegicus		ENSRNOG00000084413
drosophila_melanogaster	rgn	FBGN0261258
caenorhabditis_elegans		WBGENE00009156
caenorhabditis_elegans		WBGENE00013008

Paralogs (23): CD69 (ENSG00000110848), CLEC2B (ENSG00000110852), KLRB1 (ENSG00000111796), KLRD1 (ENSG00000134539), KLRC1 (ENSG00000134545), KLRG1 (ENSG00000139187), KLRF1 (ENSG00000150045), CLEC1A (ENSG00000150048), CLEC1B (ENSG00000165682), CLEC7A (ENSG00000172243), CLEC12A (ENSG00000172322), OLR1 (ENSG00000173391), KLRC4 (ENSG00000183542), CLEC2A (ENSG00000188393), KLRG2 (ENSG00000188883), CLEC9A (ENSG00000197992), KLRC2 (ENSG00000205809), KLRC3 (ENSG00000205810), KLRK1 (ENSG00000213809), CLEC2L (ENSG00000236279), CLEC12B (ENSG00000256660), KLRF2 (ENSG00000256797), CLEC5A (ENSG00000258227)

Protein

Protein identifiers

C-type lectin domain family 2 member D — Q9UHP7 (reviewed: Q9UHP7)

Alternative names: Lectin-like NK cell receptor, Lectin-like transcript 1, Osteoclast inhibitory lectin

All UniProt accessions (9): Q9UHP7, A0A0C4DG81, A0A0C4DGG4, F5H0P0, F5H5U4, F8WF99, H0YGG6, H0YH49, W8JXM2

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for KLRB1 that protects target cells against natural killer cell-mediated lysis. Inhibits osteoclast formation. Inhibits bone resorption. Modulates the release of interferon-gamma. Binds high molecular weight sulfated glycosaminoglycans.

Subunit / interactions. Homodimer; disulfide-linked.

Subcellular location. Cell membrane Endoplasmic reticulum Endoplasmic reticulum.

Tissue specificity. Detected in peripheral blood leukocytes, osteoblasts, lymph node, thymus and spleen. Isoform 1, isoform 2 and isoform 4 are expressed in T- and B-lymphocytes, and at lower levels in NK cells. They are also expressed in B-cell lines and LPS-matured monocyte-derived dendritic cells.

Post-translational modifications. N-glycosylated.

Induction. Up-regulated by IL1A/interleukin-1 alpha and prostaglandin E2 in cultured osteogenic sarcoma cells.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UHP7-1	1	yes
Q9UHP7-2	3
Q9UHP7-3	2
Q9UHP7-5	4
Q9UHP7-6	5
Q9UHP7-7	6

RefSeq proteins (5): NP_001004419, NP_001184246, NP_001184247, NP_001184248, NP_037401* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR033992	NKR-like_CTLD	Domain
IPR050828	C-type_lectin/matrix_domain	Family

Pfam: PF00059

UniProt features (27 total): strand 8, splice variant 6, topological domain 2, sequence variant 2, helix 2, glycosylation site 2, disulfide bond 2, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4QKH	X-RAY DIFFRACTION	1.8
4QKI	X-RAY DIFFRACTION	1.8
5MGT	X-RAY DIFFRACTION	1.9
4QKG	X-RAY DIFFRACTION	1.95
4WCO	X-RAY DIFFRACTION	2.46
4QKJ	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHP7-F1	86.68	0.71

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): 75–86, 103–184

Glycosylation sites (2): 95, 147

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

MSigDB gene sets: 204 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, ZHAN_MULTIPLE_MYELOMA_CD1_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_ALPHA_BETA_T_CELL_ACTIVATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_B_UP, GOMF_SIGNALING_RECEPTOR_BINDING, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, ZHENG_BOUND_BY_FOXP3, MARSON_BOUND_BY_FOXP3_STIMULATED

GO Biological Process (1): cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (3): transmembrane signaling receptor activity (GO:0004888), carbohydrate binding (GO:0030246), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
signal transduction	1
signaling receptor activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

1060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC2D	KLRB1	Q12918	999
CLEC2D	IFNG	P01579	608
CLEC2D	KLRC1	P26715	597
CLEC2D	CLEC1B	Q9P126	563
CLEC2D	KLRD1	Q13241	561
CLEC2D	CCR6	P51684	557
CLEC2D	LAIR1	Q6GTX8	551
CLEC2D	TIGIT	Q495A1	548
CLEC2D	HAVCR2	Q8TDQ0	538
CLEC2D	CLEC4A	Q9UMR7	519
CLEC2D	CCRL2	O00421	519
CLEC2D	IL22	Q9GZX6	511
CLEC2D	ITGB7	P26010	491
CLEC2D	IL23R	Q5VWK5	485
CLEC2D	KLRG1	Q96E93	484

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CLEC2D	KLRB1	psi-mi:“MI:0407”(direct interaction)	0.440
CLEC2D	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CLEC2D	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	ATP9A	psi-mi:“MI:0914”(association)	0.350

BioGRID (252): DNAJC1 (Affinity Capture-MS), SLC22A23 (Affinity Capture-MS), KIAA1586 (Affinity Capture-MS), FANCL (Affinity Capture-MS), SLC7A3 (Affinity Capture-MS), SUSD1 (Affinity Capture-MS), ATP8B2 (Affinity Capture-MS), FAM69A (Affinity Capture-MS), NXPE3 (Affinity Capture-MS), TMEM120A (Affinity Capture-MS), GPR50 (Affinity Capture-MS), ST6GALNAC3 (Affinity Capture-MS), GLRB (Affinity Capture-MS), LPHN1 (Affinity Capture-MS), ECEL1 (Affinity Capture-MS)

ESM2 similar proteins: A4KWA1, D3W0D1, D4AD02, O54709, O70215, O88713, P20937, P26715, P27471, P27811, P27812, P27814, Q07108, Q0ZUP0, Q0ZUP1, Q12918, Q149M0, Q2HXU8, Q2NL33, Q5NKN2, Q5NKN4, Q5QGZ9, Q60652, Q60654, Q63378, Q64335, Q67EQ0, Q6QLQ4, Q6UXN8, Q80XD9, Q80ZC8, Q8BRU4, Q8BWY2, Q8C1T8, Q8CJC7, Q8MI05, Q8NC01, Q8VD98, Q8VI21, Q95MI5

Diamond homologs: A4KWA5, A4KWA6, A4KWA8, O70156, O89335, P06734, P08290, P0C7M9, P14370, P37217, P49259, P79391, Q07108, Q0H8B9, Q5M9I1, Q5QGZ9, Q60660, Q6QLQ4, Q6UVW9, Q6UXN8, Q80XD9, Q8BWY2, Q8C1T8, Q8N1N0, Q8VI21, Q91V08, Q92478, Q925N7, Q9D676, Q9UBG0, Q9UHP7, Q9WVF9, Q9XTA8, A4KWA1, P02706, P0C7M8, P14371, P24721, P26715, P26717

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1045 predictions. Top by Δscore:

Variant	Effect	Δscore
12:9669792:CCAG:C	donor_loss	1.0000
12:9669795:GG:G	donor_loss	1.0000
12:9669796:G:C	donor_loss	1.0000
12:9687897:TTCA:T	acceptor_loss	1.0000
12:9687898:TCA:T	acceptor_loss	1.0000
12:9687899:CA:C	acceptor_loss	1.0000
12:9687900:A:AG	acceptor_gain	1.0000
12:9687900:A:AT	acceptor_loss	1.0000
12:9687901:G:GA	acceptor_gain	1.0000
12:9687901:GC:G	acceptor_gain	1.0000
12:9687901:GCA:G	acceptor_gain	1.0000
12:9694838:G:GT	donor_gain	1.0000
12:9669795:GGT:G	donor_gain	0.9900
12:9669796:GT:G	donor_gain	0.9900
12:9681031:GCG:G	donor_gain	0.9900
12:9681034:G:GG	donor_gain	0.9900
12:9687890:T:G	acceptor_gain	0.9900
12:9687894:A:AG	acceptor_gain	0.9900
12:9687895:T:G	acceptor_gain	0.9900
12:9687901:GCAA:G	acceptor_gain	0.9900
12:9687901:GCAAT:G	acceptor_gain	0.9900
12:9687981:A:T	donor_gain	0.9900
12:9688067:TTGA:T	donor_gain	0.9900
12:9692822:T:TA	acceptor_gain	0.9900
12:9692826:A:AG	acceptor_gain	0.9900
12:9692827:G:GG	acceptor_gain	0.9900
12:9694838:G:T	donor_gain	0.9900
12:9669792:CCAGG:C	donor_gain	0.9800
12:9669793:CAGGT:C	donor_gain	0.9800
12:9669794:AGGT:A	donor_gain	0.9800

AlphaMissense

1273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:9692866:G:C	W132C	0.998
12:9692866:G:T	W132C	0.998
12:9688036:T:A	C103S	0.996
12:9688037:G:A	C103Y	0.996
12:9688037:G:C	C103S	0.996
12:9692864:T:A	W132R	0.996
12:9692864:T:C	W132R	0.996
12:9692899:G:C	W143C	0.996
12:9692899:G:T	W143C	0.996
12:9694795:T:C	L166S	0.995
12:9694815:A:C	S173R	0.995
12:9694817:T:A	S173R	0.995
12:9694817:T:G	S173R	0.995
12:9694838:G:C	R180S	0.995
12:9694838:G:T	R180S	0.995
12:9688024:A:C	S99R	0.994
12:9688026:T:A	S99R	0.994
12:9688026:T:G	S99R	0.994
12:9692848:A:C	K126N	0.994
12:9692848:A:T	K126N	0.994
12:9692897:T:A	W143R	0.994
12:9692897:T:C	W143R	0.994
12:9694842:T:A	W182R	0.994
12:9694842:T:C	W182R	0.994
12:9694848:T:A	C184S	0.994
12:9694849:G:C	C184S	0.994
12:9687994:T:C	F89L	0.993
12:9687996:T:A	F89L	0.993
12:9687996:T:G	F89L	0.993
12:9692905:G:C	W145C	0.993

dbSNP variants (sampled 300 via entrez): RS1000059644 (12:9699830 C>T), RS1000113739 (12:9699570 CTT>C), RS1000162318 (12:9671301 G>A), RS1000364152 (12:9677799 A>C,G), RS1000401303 (12:9686413 A>G), RS1000530015 (12:9680696 A>G,T), RS1000545837 (12:9673405 A>G), RS1000575628 (12:9692995 G>A), RS1000750811 (12:9690004 C>T), RS1000775218 (12:9667962 C>G), RS1000818150 (12:9680544 T>C), RS1001018916 (12:9698278 A>G), RS1001205856 (12:9689617 A>G,T), RS1001470836 (12:9687232 A>C,G), RS1001585625 (12:9687551 C>T)

Disease associations

OMIM: gene MIM:605659 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST009361_1	HDL cholesterol levels x short total sleep time interaction (1df test)	7.000000e-08
GCST009367_10	HDL cholesterol levels x short total sleep time interaction (2df test)	3.000000e-06
GCST009367_6	HDL cholesterol levels x short total sleep time interaction (2df test)	5.000000e-12
GCST009597_273	Multiple sclerosis	5.000000e-24
GCST010571_55	Autoimmune thyroid disease	2.000000e-24
GCST010571_98	Autoimmune thyroid disease	9.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

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
rs1560011	CLEC2D		0.00	0

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Calcitriol	decreases expression, increases expression	2
Nickel	increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
tebuconazole	decreases expression	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Troglitazone	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Demecolcine	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Diuron	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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