CLEC4C

Summary

CLEC4C (C-type lectin domain family 4 member C, HGNC:13258) is a protein-coding gene on chromosome 12p13.31, encoding C-type lectin domain family 4 member C (Q8WTT0). Lectin-type cell surface receptor which may play a role in antigen capturing by dendritic cells.

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 dendritic cell function. Two transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 170482 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• MANE Select transcript: NM_001371390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13258
Approved symbol	CLEC4C
Name	C-type lectin domain family 4 member C
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	HECL, DLEC, BDCA2, CD303
Ensembl gene	ENSG00000198178
Ensembl biotype	protein_coding
OMIM	606677
Entrez	170482

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000354629, ENST00000360345, ENST00000537530, ENST00000540085, ENST00000542353, ENST00000543765, ENST00000850847, ENST00000850852

RefSeq mRNA: 4 — MANE Select: NM_001371390 NM_001371390, NM_001371391, NM_130441, NM_203503

CCDS: CCDS8583, CCDS8584

Canonical transcript exons

ENST00000360345 — 6 exons

Exon	Start	End
ENSE00001162060	7737429	7737574
ENSE00001162068	7741421	7741531
ENSE00001432328	7747318	7747375
ENSE00001722633	7730797	7730912
ENSE00003906694	7729383	7729740
ENSE00004282503	7746331	7746423

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 82.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6124 / max 321.1429, expressed in 69 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129284	0.4387	38
129286	0.0761	28
129283	0.0759	11
129285	0.0216	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	82.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.33	gold quality
buccal mucosa cell	CL:0002336	79.82	gold quality
leukocyte	CL:0000738	78.95	gold quality
monocyte	CL:0000576	78.89	gold quality
granulocyte	CL:0000094	75.54	gold quality
oocyte	CL:0000023	74.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.82	gold quality
blood	UBERON:0000178	65.86	gold quality
bone marrow cell	CL:0002092	65.70	gold quality
vermiform appendix	UBERON:0001154	63.72	gold quality
lymph node	UBERON:0000029	63.48	gold quality
bone marrow	UBERON:0002371	61.56	gold quality
sperm	CL:0000019	60.98	silver quality
caecum	UBERON:0001153	58.60	gold quality
gall bladder	UBERON:0002110	58.03	gold quality
tonsil	UBERON:0002372	46.52	gold quality
smooth muscle tissue	UBERON:0001135	45.94	gold quality
palpebral conjunctiva	UBERON:0001812	45.42	silver quality
lateral nuclear group of thalamus	UBERON:0002736	45.36	gold quality
testis	UBERON:0000473	45.16	gold quality
substantia nigra pars reticulata	UBERON:0001966	44.53	gold quality
right testis	UBERON:0004534	44.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
amniotic fluid	UBERON:0000173	42.98	gold quality
spleen	UBERON:0002106	42.98	gold quality
adult organism	UBERON:0007023	42.39	gold quality
trabecular bone tissue	UBERON:0002483	42.21	silver quality
rectum	UBERON:0001052	42.09	gold quality
left testis	UBERON:0004533	41.97	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	332.79
E-CURD-122	yes	15.28
E-MTAB-8498	yes	14.29
E-CURD-112	yes	13.46
E-MTAB-6075	yes	12.79
E-HCAD-10	yes	8.84
E-ANND-3	yes	2.60
E-MTAB-6386	no	1.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TCF4

miRNA regulators (miRDB)

19 targeting CLEC4C, 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-3646	100.00	73.56	5283
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-595	98.25	67.44	699
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-5189-3P	97.52	66.33	487
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-6789-5P	94.05	66.19	285

Literature-anchored findings (GeneRIF, showing 19)

• Data suggest that by associating with Fc epsilon RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of plasmacytoid dendritic cells. (PMID:17850179)
• Triggering CD303 leads to tyrosine phosphorylation of Syk, Slp65, PLCgamma2 and cytoskeletal proteins. CD303 signaling is linked with internalization by clathrin-mediated endocytosis. (PMID:18022864)
• results suggest that downregulation of BDCA2 expression on plasmacytoid dendritic cells (pDCs) may reflect the activation of pDCs accumulated in systemic lupus erythematosus patients & may be one marker for indication of disease activity of SLE patients (PMID:18684674)
• Engagement of BDCA-2 blocks TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells. (PMID:19577819)
• Indoleamine 2,3-deoxigenase positive plasmacytoid dentritic cells are the classical BDCA2 positive cells in melanoma lymph nodes (PMID:19829303)
• Expression of dendritic cell markers CD11c/BDCA-1 and CD123/BDCA-2 in coronary artery disease upon activation in whole blood. (PMID:20888334)
• Accumulation of BDCA-1 and BDCA-2 around neovessels showed that mDCs and pDCs are recruited to advanced arteriosclerotic plaques. (PMID:21436634)
• Human C-type lectin domain family 4, member C (CLEC4C/BDCA-2/CD303) is a receptor for asialo-galactosyl-oligosaccharides. (PMID:21880719)
• Data show that HCV envelope glycoprotein E2 is a novel ligand of blood dendritic cells antigen 2 (BDCA-2). (PMID:23053572)
• We show the crystal structures of a carbohydrate recognition domain (CRD) of human C-type lectin receptor blood dendritic cell antigen-2 (BDCA2). (PMID:24425442)
• Reduction in Treg numbers following Ag delivery to BDCA2 restored both CD4(+) T cell activation and Ab responses, demonstrating that Tregs were required for the observed tolerance. (PMID:24829416)
• Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset. (PMID:25779340)
• BDCA-2 binds selectively to glycans containing the epitope Galbeta1-3/4GlcNAcbeta1-2Man. (PMID:25995448)
• decrease in the surface expression of CLEC4C and the endoplasmic reticulum localization of the mutant construct were observed (PMID:26943047)
• Identification of serum glycoprotein ligands for the immunomodulatory receptor blood dendritic cell antigen 2. (PMID:29796630)
• 24F4A (BIIB059) is an antibody targeting BDCA2. (PMID:30846987)
• Re-evaluation of human BDCA-2+ DC during acute sterile skin inflammation. (PMID:31845972)
• Zika Virus Inhibits IFN-alpha Response by Human Plasmacytoid Dendritic Cells and Induces NS1-Dependent Triggering of CD303 (BDCA-2) Signaling. (PMID:33193389)
• The differentiation of new human CD303(+) Plasmacytoid dendritic cell subpopulations expressing CD205 and/or CD103 regulated by Non-Small-Cell lung cancer cells. (PMID:34298400)

Cross-species orthologs

28 orthologs

Organism	Symbol	Gene ID
danio_rerio	asgr1c.2	ENSDARG00000046092
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	Clec4b1	ENSMUSG00000030147
mus_musculus	Clec4a2	ENSMUSG00000030148
mus_musculus	Clec4a3	ENSMUSG00000043832
mus_musculus	Clec4a4	ENSMUSG00000059639
mus_musculus	Clec4b2	ENSMUSG00000067767
rattus_norvegicus	Clec4a3	ENSRNOG00000010018
rattus_norvegicus	Clec4a	ENSRNOG00000010045
rattus_norvegicus	Clec4b2	ENSRNOG00000027655
rattus_norvegicus	Clec4a2	ENSRNOG00000030012
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), CLEC4A (ENSG00000111729), CD207 (ENSG00000116031), CLEC10A (ENSG00000132514), ASGR1 (ENSG00000141505), CLEC4F (ENSG00000152672), ASGR2 (ENSG00000161944), CLEC4E (ENSG00000166523), CLEC4D (ENSG00000166527), CLEC4G (ENSG00000182566), CLEC17A (ENSG00000187912), CLEC6A (ENSG00000205846)

Protein

Protein identifiers

C-type lectin domain family 4 member C — Q8WTT0 (reviewed: Q8WTT0)

Alternative names: Blood dendritic cell antigen 2, C-type lectin superfamily member 7, Dendritic lectin

All UniProt accessions (3): Q8WTT0, H0YFH6, H0YGB2

UniProt curated annotations — full annotation on UniProt →

Function. Lectin-type cell surface receptor which may play a role in antigen capturing by dendritic cells. Specifically recognizes non-sialylated galactose-terminated biantennary glycans containing the trisaccharide epitope Gal(beta1-3/4)GlcNAc(beta1-2)Man. Binds to serum IgG. Efficiently targets ligand into antigen-processing and peptide-loading compartments for presentation to T-cells. May mediate potent inhibition of induction of IFN-alpha/beta expression in plasmacytoid dendritic cells. May act as a signaling receptor that activates protein-tyrosine kinases and mobilizes intracellular calcium.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in plasmacytoid dendritic cells (PDCs). Constitutively expressed in immature monocyte-derived dendritic cells (iMDDC) and is significantly down-regulated upon maturation with LPS but not with TNF.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WTT0-1	1	yes
Q8WTT0-2	2

RefSeq proteins (4): NP_001358319, NP_001358320, NP_569708, NP_987099 (=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
IPR050111	C-type_lectin/snaclec_domain	Family

Pfam: PF00059

UniProt features (46 total): binding site 11, strand 11, mutagenesis site 5, disulfide bond 4, helix 4, glycosylation site 3, topological domain 2, chain 1, transmembrane region 1, splice variant 1, sequence conflict 1, domain 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4ZES	X-RAY DIFFRACTION	1.65
3WBP	X-RAY DIFFRACTION	1.8
3WBR	X-RAY DIFFRACTION	2.2
3WBQ	X-RAY DIFFRACTION	2.3
4ZET	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WTT0-F1	91.84	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.

Ligand- & substrate-binding residues (11): 184–186; 194–195; 194; 194; 195; 202; 139; 172; 174; 178; 178

Disulfide bonds (4): 70–82, 83–94, 111–206, 180–198

Glycosylation sites (3): 110, 137, 164

Mutagenesis-validated functional residues (5):

Position	Phenotype
139	significantly impairs carbohydrate binding for the trisaccharide gal(beta1-3/4)glcnac(beta1-2)man.
184	abolishes carbohydrate binding for the trisaccharide gal(beta1-3/4)glcnac(beta1-2)man.
186	significantly impairs carbohydrate binding for the trisaccharide gal(beta1-3/4)glcnac(beta1-2)man.
200	significantly impairs carbohydrate binding for the trisaccharide gal(beta1-3/4)glcnac(beta1-2)man.
202	significantly impairs carbohydrate binding for the trisaccharide gal(beta1-3/4)glcnac(beta1-2)man.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5621480	Dectin-2 family
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 57 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOCC_CELL_SURFACE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_ADAPTIVE_IMMUNE_RESPONSE, BROWN_MYELOID_CELL_DEVELOPMENT_UP, GOBP_RESPONSE_TO_FUNGUS, GOCC_SECRETORY_VESICLE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_SIDE_OF_MEMBRANE, CAMPS_COLON_CANCER_COPY_NUMBER_DN, GOCC_EXTERNAL_SIDE_OF_PLASMA_MEMBRANE, GOBP_ANTIFUNGAL_INNATE_IMMUNE_RESPONSE, GOCC_TERTIARY_GRANULE

GO Biological Process (4): adaptive immune response (GO:0002250), antifungal innate immune response (GO:0061760), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (4): carbohydrate binding (GO:0030246), pattern recognition receptor activity (GO:0038187), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), secretory granule membrane (GO:0030667), tertiary granule membrane (GO:0070821), ficolin-1-rich granule membrane (GO:0101003), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
C-type lectin receptors (CLRs)	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	2
binding	2
secretory granule membrane	2
tertiary granule	2
innate immune response	1
defense response to fungus	1
biological_process	1
defense response to symbiont	1
signaling receptor activity	1
cation binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
ficolin-1-rich granule	1
cellular anatomical structure	1

Protein interactions and networks

STRING

997 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC4C	IL3RA	P26951	940
CLEC4C	CD1C	P29017	914
CLEC4C	THBD	P07204	898
CLEC4C	NRP1	O14786	889
CLEC4C	ITGAX	P20702	856
CLEC4C	ITIH4	Q14624	802
CLEC4C	LILRA4	P59901	778
CLEC4C	CD2	P06729	707
CLEC4C	FCER1A	P12319	678
CLEC4C	CD19	P15391	673
CLEC4C	TLR7	Q9NYK1	668
CLEC4C	NCAM1	P13591	667
CLEC4C	IFNA13	P01562	664
CLEC4C	TLR9	Q9NR96	651
CLEC4C	CD4	P01730	643

IntAct

16 interactions, top by confidence:

A	B	Type	Score
MAL	CLEC4C	psi-mi:“MI:0915”(physical association)	0.600
CLDN22	CLEC4C	psi-mi:“MI:0915”(physical association)	0.560
KTN1	CLEC4C	psi-mi:“MI:0915”(physical association)	0.560
CLEC4C	FCER1G	psi-mi:“MI:0915”(physical association)	0.400
CLEC4C	SLC25A6	psi-mi:“MI:0914”(association)	0.350
CLEC4C	CLGN	psi-mi:“MI:0914”(association)	0.350
CLEC4C	ENTPD6	psi-mi:“MI:0914”(association)	0.350
MAL	CLEC4C	psi-mi:“MI:0915”(physical association)	0.000
CLDN22	CLEC4C	psi-mi:“MI:0915”(physical association)	0.000
KTN1	CLEC4C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): CLEC4C (Two-hybrid), CLEC4C (Two-hybrid), CLEC4C (Two-hybrid), NEK2 (Two-hybrid), NEK2 (Affinity Capture-Western), CLEC4C (Affinity Capture-Western), TUBA1B (Affinity Capture-MS), SLC25A6 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), ATP8B2 (Affinity Capture-MS), SLC25A30 (Affinity Capture-MS), INTS7 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), BRF1 (Affinity Capture-MS)

ESM2 similar proteins: A4KWA1, D3W0D1, D4AD02, O54709, O70215, O88713, P20937, P26715, P26717, P26718, P27471, P27811, P27812, P27814, Q07108, Q0ZUP0, Q0ZUP1, Q12918, Q149M0, Q2HXU8, Q2NL33, Q5NKN2, Q5NKN4, Q5QGZ9, Q60651, Q60652, Q63378, Q67EQ0, Q6QLQ4, Q6UXN8, Q80XD9, Q80ZC8, Q8BRU4, Q8CJC7, Q8MI05, Q8MJH1, Q8VD98, Q8VI21, Q8WTT0, 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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

791 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7730795:A:AC	donor_gain	1.0000
12:7730796:C:CC	donor_gain	1.0000
12:7730796:CGTGA:C	donor_gain	1.0000
12:7730868:C:CT	acceptor_gain	1.0000
12:7730868:C:T	acceptor_gain	1.0000
12:7730869:A:T	acceptor_gain	1.0000
12:7737579:CCAAA:C	acceptor_gain	1.0000
12:7737580:C:T	acceptor_gain	1.0000
12:7737580:CAAA:C	acceptor_gain	1.0000
12:7737581:A:T	acceptor_gain	1.0000
12:7737583:A:AC	acceptor_gain	1.0000
12:7737587:G:GC	acceptor_gain	1.0000
12:7737589:A:AC	acceptor_gain	1.0000
12:7737589:A:C	acceptor_gain	1.0000
12:7741532:C:CC	acceptor_gain	1.0000
12:7747485:T:C	acceptor_gain	1.0000
12:7729739:ATC:A	acceptor_loss	0.9900
12:7729740:TC:T	acceptor_loss	0.9900
12:7729741:C:CC	acceptor_gain	0.9900
12:7729741:CTGA:C	acceptor_loss	0.9900
12:7729742:T:G	acceptor_loss	0.9900
12:7730789:ATAC:A	donor_loss	0.9900
12:7730791:ACT:A	donor_loss	0.9900
12:7730792:CT:C	donor_loss	0.9900
12:7730793:TCA:T	donor_loss	0.9900
12:7730794:CAC:C	donor_loss	0.9900
12:7730795:AC:A	donor_loss	0.9900
12:7730910:ATCC:A	acceptor_loss	0.9900
12:7730911:TC:T	acceptor_gain	0.9900
12:7730911:TCC:T	acceptor_loss	0.9900

AlphaMissense

1421 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7729734:C:A	W168C	0.996
12:7729734:C:G	W168C	0.996
12:7730829:C:A	W155C	0.996
12:7730829:C:G	W155C	0.996
12:7730835:C:A	W153C	0.994
12:7730835:C:G	W153C	0.994
12:7729621:C:G	C206S	0.992
12:7729622:A:T	C206S	0.992
12:7729659:C:A	W193C	0.990
12:7729659:C:G	W193C	0.990
12:7729661:A:G	W193R	0.990
12:7729661:A:T	W193R	0.990
12:7730831:A:G	W155R	0.990
12:7730831:A:T	W155R	0.990
12:7737498:C:A	W104C	0.990
12:7737498:C:G	W104C	0.990
12:7737549:C:A	W87C	0.990
12:7737549:C:G	W87C	0.990
12:7729699:C:G	C180S	0.989
12:7729700:A:T	C180S	0.989
12:7737478:C:G	C111S	0.988
12:7737479:A:T	C111S	0.988
12:7729665:C:A	W191C	0.987
12:7729665:C:G	W191C	0.987
12:7737477:A:C	C111W	0.986
12:7729736:A:G	W168R	0.982
12:7729736:A:T	W168R	0.982
12:7737478:C:T	C111Y	0.982
12:7737529:C:G	C94S	0.981
12:7737530:A:T	C94S	0.981

dbSNP variants (sampled 300 via entrez): RS1000275741 (12:7736738 C>T), RS1000513576 (12:7745208 G>C,T), RS1000529117 (12:7729010 C>T), RS1000689936 (12:7736982 A>G), RS1000770035 (12:7730610 A>C), RS1000799142 (12:7739911 C>T), RS1000999199 (12:7734121 T>C), RS1001159707 (12:7745251 C>T), RS1001253434 (12:7746048 T>C), RS1001275796 (12:7745537 A>G), RS1001607843 (12:7730736 G>A), RS1001775526 (12:7740557 C>T), RS1002034197 (12:7731193 C>G), RS1002137886 (12:7749774 C>A,T), RS1002174200 (12:7734967 G>A,T)

Disease associations

OMIM: gene MIM:606677 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	Autosomal dominant

Mondo (2): primary ovarian failure (MONDO:0005387), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_468	Blood protein levels	0.000000e+00

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2176855 (SINGLE PROTEIN)

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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
kojic acid	decreases expression	1
bisphenol S	increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Formaldehyde	decreases expression	1
Nickel	increases expression	1
Silicon Dioxide	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2185430	Binding	Displacement of biotinylated-TM PAA from human DLEC at 50 mM after 3 hrs by colorimetry	Target Selectivity of FimH Antagonists. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 spontaneously immortalized cell line, 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E4J6	Genomeditech Jurkat H_CLEC4C(BDCA2) Reporter	Cancer cell line	Male
CVCL_E5IE	CHO-K1/BDCA2	Spontaneously immortalized cell line	Female
CVCL_E5IG	CHO-K1/BDCA2 and FcER1G	Spontaneously immortalized cell line	Female
CVCL_E6Q2	Genomeditech CHO-K1 H_CLEC4C(BDCA2)+FCER1G	Spontaneously immortalized cell line	Female
CVCL_E6TS	Genomeditech HEK-293 H_CLEC4C(BDCA2)+FCER1G	Transformed cell line	Female
CVCL_E6VR	Genomeditech Jurkat H_CLEC4C(BDCA2)+FCER1G	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease