CLEC4A

Summary

CLEC4A (C-type lectin domain family 4 member A, HGNC:13257) is a protein-coding gene on chromosome 12p13.31, encoding C-type lectin domain family 4 member A (Q9UMR7). C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca(2+)-dependent manner.

This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.

Source: NCBI Gene 50856 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_016184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13257
Approved symbol	CLEC4A
Name	C-type lectin domain family 4 member A
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	DCIR, DDB27, CD367, hDCIR
Ensembl gene	ENSG00000111729
Ensembl biotype	protein_coding
OMIM	605306
Entrez	50856

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000229332, ENST00000345999, ENST00000352620, ENST00000360500, ENST00000641376

RefSeq mRNA: 4 — MANE Select: NM_016184 NM_016184, NM_194447, NM_194448, NM_194450

CCDS: CCDS41745, CCDS8590, CCDS8591, CCDS8592

Canonical transcript exons

ENST00000229332 — 6 exons

Exon	Start	End
ENSE00000867815	8125561	8125677
ENSE00000867817	8129264	8129362
ENSE00000936954	8135585	8135736
ENSE00000936956	8138140	8138607
ENSE00001405263	8123617	8123960
ENSE00003652871	8136788	8136903

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 98.25.

FANTOM5 (CAGE): breadth broad, TPM avg 5.6752 / max 331.6875, expressed in 302 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123954	2.7999	225
123952	1.5143	203
123953	0.7267	169
123955	0.2381	58
123950	0.2161	98
123951	0.1299	71
123949	0.0501	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.25	gold quality
leukocyte	CL:0000738	98.13	gold quality
granulocyte	CL:0000094	96.17	gold quality
blood	UBERON:0000178	93.01	gold quality
vermiform appendix	UBERON:0001154	88.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.13	gold quality
spleen	UBERON:0002106	85.14	gold quality
bone marrow	UBERON:0002371	84.62	gold quality
bone marrow cell	CL:0002092	83.43	gold quality
upper lobe of left lung	UBERON:0008952	79.41	gold quality
right lung	UBERON:0002167	78.86	gold quality
lymph node	UBERON:0000029	78.63	gold quality
gall bladder	UBERON:0002110	77.71	gold quality
tibial nerve	UBERON:0001323	76.41	gold quality
lung	UBERON:0002048	76.11	gold quality
rectum	UBERON:0001052	75.93	gold quality
placenta	UBERON:0001987	75.74	gold quality
right ovary	UBERON:0002118	75.72	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.66	gold quality
right lobe of liver	UBERON:0001114	75.47	gold quality
adipose tissue	UBERON:0001013	75.21	gold quality
descending thoracic aorta	UBERON:0002345	75.15	gold quality
right coronary artery	UBERON:0001625	75.14	gold quality
smooth muscle tissue	UBERON:0001135	75.12	gold quality
left ovary	UBERON:0002119	75.11	gold quality
omental fat pad	UBERON:0010414	74.79	gold quality
duodenum	UBERON:0002114	74.75	gold quality
ovary	UBERON:0000992	74.25	gold quality
endocervix	UBERON:0000458	74.04	gold quality
endometrium	UBERON:0001295	73.98	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	24.22
E-MTAB-6678	yes	8.05
E-ANND-3	yes	7.58
E-MTAB-9801	yes	6.48
E-ENAD-17	no	112.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting CLEC4A, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-562	97.66	65.63	698
HSA-MIR-1266-3P	96.23	66.36	778

Literature-anchored findings (GeneRIF, showing 19)

• CLECSF6 is involved in the control of inflammation in neutrophils (PMID:14550269)
• The phosphorylation of SHP-2 by GM-CSF promotes the binding of SHP-2 to the GM-CSF receptor to the disadvantage of CLECSF6. (PMID:16360206)
• Human APLEC and DCIR may be associated with susceptibility to anti-CCP-negative rheumatoid arthritis. (PMID:17665455)
• The data show that targeting of DCIR can modulate human plasmacytoid dendritic cell function and may be applied in disease prevention and treatment. (PMID:18258799)
• The mRNA expression from the four known transcripts of DCIR in IFN-gamma-treated human leukocytes together with fine mapping across the locus was analyzed. (PMID:18480830)
• can participate in the capture of HIV-1 and promote infection in trans and in cis of autologous CD4(+) T cells from human immature monocyte-derived DCs. (PMID:18541725)
• DCIR as an antigen presenting cell receptor that is endocytosed efficiently in a clathrin-dependent manner and negatively affects TLR8-mediated cytokine production. (PMID:19028959)
• Data show that antigen targeting via the DCIR receptor allows activation of specific CD8(+) T-cell immunity. (PMID:20530286)
• An involvement of ITIM domain in HIV-1-mediated signaling events and a relationship between phosphorylation events and DCIR function with respect to HIV-1 biology. (PMID:21536857)
• No association was found between our inflammatory bowel disease cohort and the candidate single nucleotide polymorphisms for DCIR (CD/HC: P=0.22 and UC/HC: P=0.41) (PMID:22664939)
• Data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA. (PMID:22829930)
• this study shows that sulfo-Lewis(a) is a high affinity ligand for DCIR and that DCIR interacts with ligands from both pathogenic and endogenous origin of which most are shared by DC-SIGN. (PMID:24239607)
• DCIR SNP rs2377422 is a novel genetic susceptibility factor for both SLE and primary SS. (PMID:26429306)
• Authors have determined the structure, tissue distribution, and molecular function of the cartilage-specific lectin CLEC3A and show that CLEC3A binds to plasminogen and participates in tPA-mediated plasminogen activation. (PMID:29146595)
• Pivotal role of the carbohydrate recognition domain in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory function in murine conventional dendritic cells in vitro. (PMID:32415968)
• DCIR and its ligand asialo-biantennary N-glycan regulate DC function and osteoclastogenesis. (PMID:34817551)
• Differential expression of immune-regulatory proteins C5AR1, CLEC4A and NLRP3 on peripheral blood mononuclear cells in early-stage non-small cell lung cancer patients. (PMID:36323738)
• DCIR suppresses osteoclastic proliferation and resorption by downregulating M-CSF and RANKL signaling. (PMID:37266426)
• The C-type lectin DCIR contributes to the immune response and pathogenesis of colorectal cancer. (PMID:38532110)

Cross-species orthologs

22 orthologs

Organism	Symbol	Gene ID
danio_rerio	asgr1c.2	ENSDARG00000046092
danio_rerio	asgrl1	ENSDARG00000046142
danio_rerio	si:dkey-61f9.1	ENSDARG00000070414
danio_rerio	asgr1a	ENSDARG00000095963
danio_rerio	si:cabz01007816.2	ENSDARG00000102537
danio_rerio	asgr1b	ENSDARG00000103480
danio_rerio	si:ch211-283g2.5	ENSDARG00000108953
danio_rerio		ENSDARG00000111755
danio_rerio		ENSDARG00000112842
mus_musculus	Clec4a1	ENSMUSG00000049037
rattus_norvegicus	Clec4a1	ENSRNOG00000042139
drosophila_melanogaster	tfc	FBGN0035199
drosophila_melanogaster	CG14866	FBGN0038315
drosophila_melanogaster	lectin-46Cb	FBGN0040092
drosophila_melanogaster	lectin-46Ca	FBGN0040093
drosophila_melanogaster	lectin-33A	FBGN0040096
drosophila_melanogaster	CG34033	FBGN0054033
caenorhabditis_elegans	clec-87	WBGENE00007709
caenorhabditis_elegans	clec-91	WBGENE00014117
caenorhabditis_elegans		WBGENE00016088
caenorhabditis_elegans		WBGENE00018692
caenorhabditis_elegans		WBGENE00019606

Paralogs (14): CD209 (ENSG00000090659), FCER2 (ENSG00000104921), CLEC4M (ENSG00000104938), CD207 (ENSG00000116031), CLEC10A (ENSG00000132514), ASGR1 (ENSG00000141505), CLEC4F (ENSG00000152672), ASGR2 (ENSG00000161944), CLEC4E (ENSG00000166523), CLEC4D (ENSG00000166527), CLEC4G (ENSG00000182566), CLEC17A (ENSG00000187912), CLEC4C (ENSG00000198178), CLEC6A (ENSG00000205846)

Protein

Protein identifiers

C-type lectin domain family 4 member A — Q9UMR7 (reviewed: Q9UMR7)

Alternative names: C-type lectin DDB27, C-type lectin superfamily member 6, Dendritic cell immunoreceptor, Lectin-like immunoreceptor

All UniProt accessions (2): Q9UMR7, A0A286YF15

UniProt curated annotations — full annotation on UniProt →

Function. C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca(2+)-dependent manner. Involved in regulating immune reactivity. Once triggered by antigen, it is internalized by clathrin-dependent endocytosis and delivers its antigenic cargo into the antigen presentation pathway resulting in cross-priming of CD8(+) T cells. This cross-presentation and cross-priming are enhanced by TLR7 and TLR8 agonists with increased expansion of the CD8(+) T cells, high production of IFNG and TNF with reduced levels of IL4, IL5 and IL13. In plasmacytoid dendritic cells, inhibits TLR9-mediated IFNA and TNF production. May be involved via its ITIM motif (immunoreceptor tyrosine-based inhibitory motifs) in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation. (Microbial infection) Involved in the interaction between HIV-1 virus and dendritic cells. Enhances HIV-1 binding/entry and virus infection. Requires ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases.

Subunit / interactions. May interact with PTPN6 via its ITIM motif.

Subcellular location. Cell membrane.

Tissue specificity. Expressed preferentially in hematopoietic tissues. Expressed in all circulating Ag-presenting cells such as dendritic cells, myeloid cells, monocytes, macrophages, B-cells and epidermal Langerhans cells (at protein level). Expressed in peripheral blood leukocytes, neutrophils, moderate quantities in spleen, lymph node, and bone marrow, and at very low levels in thymus.

Domain organisation. Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. Involved in the interaction between HIV-1 virus and dendritic cells. Enhances HIV-1 binding/entry and virus infection. Requires ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases. ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases is required for HIV-1 binding/entry and virus infection.

Induction. TNF alpha, IL-1 alpha, and LPS, down-regulated expression at the surface of neutrophils (at protein level). Expression is decreased in dendritic cells by signals inducing their maturation (e.g. CD40 ligand, TLR9 ligands, LPS, and TNF alpha). Isoform 2: mRNA expression is up-regulated by agonists of neutrophils CSF2/GM-CSF, IL3/interleukin-3, IL4/interleukin-4 and IL13/interleukin-13.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UMR7-1	1	yes
Q9UMR7-2	2
Q9UMR7-3	3, llirV1
Q9UMR7-4	4, llirV2

RefSeq proteins (4): NP_057268, NP_919429, NP_919430, NP_919432 (=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
IPR018378	C-type_lectin_CS	Conserved_site
IPR033989	CD209-like_CTLD	Domain
IPR051379	C-type_Lectin_Receptor_IMM	Family

Pfam: PF00059

UniProt features (41 total): binding site 12, strand 8, disulfide bond 3, splice variant 3, helix 3, topological domain 2, mutagenesis site 2, chain 1, glycosylation site 1, transmembrane region 1, sequence variant 1, sequence conflict 1, turn 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5B1X	X-RAY DIFFRACTION	2.9
5B1W	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMR7-F1	84.95	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (12): 195; 197; 201; 201; 207–209; 218; 219; 231; 143; 145; 149; 195–197

Disulfide bonds (3): 106–117, 134–230, 203–222

Glycosylation sites (1): 185

Mutagenesis-validated functional residues (2):

Position	Phenotype
6	decreases hiv-1 binding/entry in cells as well as virus replication.
7	decreases hiv-1 binding/entry in cells as well as virus replication.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5621480	Dectin-2 family

MSigDB gene sets: 190 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GOCC_CELL_SURFACE, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GNF2_MCL1, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GNF2_CD1D, RAMALHO_STEMNESS_DN, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, BRN2_01, GNF2_S100A4, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN_VIA_MHC_CLASS_I

GO Biological Process (11): negative regulation of cytokine production (GO:0001818), adaptive immune response (GO:0002250), plasmacytoid dendritic cell antigen processing and presentation (GO:0002470), cell adhesion (GO:0007155), cell surface receptor signaling pathway (GO:0007166), negative regulation of tumor necrosis factor production (GO:0032720), CD8-positive, alpha-beta T cell activation (GO:0036037), antigen processing and presentation of exogenous peptide antigen via MHC class I (GO:0042590), antifungal innate immune response (GO:0061760), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (6): transmembrane signaling receptor activity (GO:0004888), calcium ion binding (GO:0005509), D-mannose binding (GO:0005537), carbohydrate binding (GO:0030246), pattern recognition receptor activity (GO:0038187), metal ion binding (GO:0046872)

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
C-type lectin receptors (CLRs)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	2
signaling receptor activity	2
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
dendritic cell antigen processing and presentation	1
cellular process	1
signal transduction	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
alpha-beta T cell activation	1
antigen processing and presentation of peptide antigen via MHC class I	1
antigen processing and presentation of exogenous peptide antigen	1
innate immune response	1
defense response to fungus	1
biological_process	1
defense response to symbiont	1
metal ion binding	1
monosaccharide binding	1
binding	1
cation binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC4A	LY75	O60449	864
CLEC4A	PTPN11	Q06124	732
CLEC4A	SLC2A3	P11169	668
CLEC4A	ITIH4	Q14624	632
CLEC4A	IL3RA	P26951	615
CLEC4A	TLR2	O60603	591
CLEC4A	APOBEC1	P41238	548
CLEC4A	SIGLEC1	Q9BZZ2	545
CLEC4A	CCR5	P51681	537
CLEC4A	CLEC7A	Q9BXN2	532
CLEC4A	CLEC2D	Q9UHP7	519
CLEC4A	FAM90A1	Q86YD7	518
CLEC4A	ICAM3	P32942	506
CLEC4A	NR0B2	Q15466	489
CLEC4A	PDCD1LG2	Q9BQ51	486

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
PSG7	CLEC4A	psi-mi:“MI:0915”(physical association)	0.400
SDK2	CLEC4A	psi-mi:“MI:0915”(physical association)	0.400
CLEC4A	RBFOX3	psi-mi:“MI:0914”(association)	0.350
CLEC4A		psi-mi:“MI:0914”(association)	0.350

BioGRID (101): CLEC4A (Two-hybrid), CLEC4A (Affinity Capture-RNA), ALCAM (Affinity Capture-MS), ND6 (Affinity Capture-MS), PXDN (Affinity Capture-MS), PCDHGC3 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), IGSF8 (Affinity Capture-MS), IGDCC3 (Affinity Capture-MS), MPZL1 (Affinity Capture-MS), FLT4 (Affinity Capture-MS), IPPK (Affinity Capture-MS), EIF2B5 (Affinity Capture-MS), ROR1 (Affinity Capture-MS), RBM14-RBM4 (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: A4KWA1, A4KWA6, P20693, P20937, P21063, P24765, P27471, P27811, P27812, P27814, P79391, Q0ZUP0, Q0ZUP1, Q12918, Q49BZ4, Q5NKN2, Q5NKN4, Q60651, Q60654, Q61830, Q63378, Q67EQ1, Q8HY06, Q8HY10, Q8HY11, Q8HY12, Q8HYC0, Q8VD98, Q8WTT0, Q90WJ8, Q91ZW8, Q925N7, Q95LG1, Q99JB4, Q9GLF3, Q9GME8, Q9H2X3, Q9JKF4, Q9NY25, Q9QZ15

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

988 predictions. Top by Δscore:

Variant	Effect	Δscore
12:8136785:CA:C	acceptor_loss	1.0000
12:8136786:AG:A	acceptor_gain	1.0000
12:8136787:GG:G	acceptor_gain	1.0000
12:8136904:G:GG	donor_gain	1.0000
12:8129262:A:AG	acceptor_gain	0.9900
12:8129263:G:GG	acceptor_gain	0.9900
12:8136786:A:AG	acceptor_gain	0.9900
12:8136787:G:GG	acceptor_gain	0.9900
12:8136787:GGA:G	acceptor_gain	0.9900
12:8136787:GGAT:G	acceptor_gain	0.9900
12:8136894:A:T	donor_gain	0.9900
12:8136898:TTCC:T	donor_gain	0.9900
12:8136899:TCCAC:T	donor_gain	0.9900
12:8136902:AC:A	donor_gain	0.9900
12:8136903:CGTGA:C	donor_loss	0.9900
12:8136904:GT:G	donor_loss	0.9900
12:8136905:T:A	donor_loss	0.9900
12:8136906:G:GA	donor_loss	0.9900
12:8136907:A:AA	donor_loss	0.9900
12:8136908:G:C	donor_loss	0.9900
12:8123956:TGCAG:T	donor_loss	0.9800
12:8123957:GCAGG:G	donor_loss	0.9800
12:8123958:CAG:C	donor_loss	0.9800
12:8123959:AG:A	donor_loss	0.9800
12:8123960:GG:G	donor_loss	0.9800
12:8123962:T:G	donor_loss	0.9800
12:8136783:CTCAG:C	acceptor_gain	0.9800
12:8136784:TCAGG:T	acceptor_gain	0.9800
12:8136785:CAGG:C	acceptor_gain	0.9800
12:8136786:AGG:A	acceptor_gain	0.9800

AlphaMissense

1575 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:8136871:G:C	W178C	0.994
12:8136871:G:T	W178C	0.994
12:8138146:G:C	W191C	0.993
12:8138146:G:T	W191C	0.993
12:8135616:G:C	W110C	0.991
12:8135616:G:T	W110C	0.991
12:8136865:G:C	W176C	0.991
12:8136865:G:T	W176C	0.991
12:8138224:G:C	W217C	0.988
12:8138224:G:T	W217C	0.988
12:8136869:T:A	W178R	0.987
12:8136869:T:C	W178R	0.987
12:8138218:G:C	W215C	0.986
12:8138218:G:T	W215C	0.986
12:8135667:G:C	W127C	0.985
12:8135667:G:T	W127C	0.985
12:8138222:T:A	W217R	0.984
12:8138222:T:C	W217R	0.984
12:8138261:T:A	C230S	0.983
12:8138262:G:C	C230S	0.983
12:8138180:T:A	C203S	0.981
12:8138181:G:C	C203S	0.981
12:8135688:T:G	C134W	0.980
12:8135701:G:C	A139P	0.980
12:8135687:G:A	C134Y	0.978
12:8135635:T:A	C117S	0.977
12:8135636:G:C	C117S	0.977
12:8135686:T:A	C134S	0.977
12:8135687:G:C	C134S	0.977
12:8135614:T:A	W110R	0.975

dbSNP variants (sampled 300 via entrez): RS1000027759 (12:8108370 A>G), RS1000075788 (12:8124926 T>C), RS1000082410 (12:8114345 C>A,G,T), RS1000215200 (12:8105421 C>T), RS1000287176 (12:8132462 T>G), RS1000383550 (12:8112584 T>C), RS1000478283 (12:8112940 A>G), RS1000559858 (12:8136487 C>T), RS1000615281 (12:8136797 T>C), RS1000623647 (12:8129803 G>T), RS1000718823 (12:8125405 A>T), RS1000946169 (12:8117167 C>T), RS1001006416 (12:8130037 T>C), RS1001059801 (12:8106284 A>G), RS1001080444 (12:8123352 T>A,C)

Disease associations

OMIM: gene MIM:605306 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: other protein — C-type lectin-like receptors (CLRs)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	decreases expression, decreases methylation, affects cotreatment	2
Nickel	decreases expression, increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
cinnamaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Pioglitazone	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Fonofos	increases methylation	1
Eugenol	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Parathion	increases methylation	1
Tobacco Smoke Pollution	increases methylation	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1CU	Ubigene THP-1 CLEC4A KO	Cancer cell line	Male

Clinical trials (associated diseases)

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