CLEC18A

Summary

CLEC18A (C-type lectin domain family 18 member A, HGNC:30388) is a protein-coding gene on chromosome 16q22.1, encoding C-type lectin domain family 18 member A (A5D8T8). Binds polysaccharides in a Ca(2+)-independent manner with a preferentially binding to fucoidan, beta-glucans and galactans.

This is one of three closely related paralogous genes on chromosome 16 encoding secreted proteins containing C-type lectin domains. These domains bind to carbohydrates in the presence of calcium, and may be involved in cell adhesion, immune response and apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 348174 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 73 total — 1 pathogenic
• MANE Select transcript: NM_001370523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30388
Approved symbol	CLEC18A
Name	C-type lectin domain family 18 member A
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000157322
Ensembl biotype	protein_coding
OMIM	616571
Entrez	348174

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 retained_intron

ENST00000288040, ENST00000393701, ENST00000449317, ENST00000561889, ENST00000565245, ENST00000565705, ENST00000568102, ENST00000568461, ENST00000615430, ENST00000889824, ENST00000966085

RefSeq mRNA: 4 — MANE Select: NM_001370523 NM_001136214, NM_001271197, NM_001370523, NM_182619

CCDS: CCDS10886

Canonical transcript exons

ENST00000288040 — 12 exons

Exon	Start	End
ENSE00002464478	69960845	69960951
ENSE00002495705	69961988	69962084
ENSE00002508577	69961586	69961715
ENSE00003466305	69960373	69960465
ENSE00003469257	69952035	69952126
ENSE00003489149	69958942	69959039
ENSE00003548144	69954334	69954573
ENSE00003577949	69962976	69963067
ENSE00003609401	69963574	69963986
ENSE00003623466	69959460	69959581
ENSE00003681160	69959739	69959846
ENSE00003733910	69951334	69951490

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 86.15.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult mammalian kidney	UBERON:0000082	86.15	gold quality
kidney	UBERON:0002113	83.14	gold quality
cortex of kidney	UBERON:0001225	81.17	gold quality
descending thoracic aorta	UBERON:0002345	81.09	gold quality
ascending aorta	UBERON:0001496	80.90	gold quality
thoracic aorta	UBERON:0001515	80.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.97	gold quality
right coronary artery	UBERON:0001625	73.93	gold quality
blood	UBERON:0000178	73.26	gold quality
granulocyte	CL:0000094	72.34	gold quality
metanephros cortex	UBERON:0010533	72.25	gold quality
left testis	UBERON:0004533	70.43	gold quality
lower esophagus mucosa	UBERON:0035834	69.73	gold quality
testis	UBERON:0000473	69.54	gold quality
mucosa of transverse colon	UBERON:0004991	68.77	gold quality
right uterine tube	UBERON:0001302	68.53	gold quality
popliteal artery	UBERON:0002250	67.86	gold quality
tibial artery	UBERON:0007610	67.82	gold quality
right testis	UBERON:0004534	67.72	gold quality
right adrenal gland cortex	UBERON:0035827	67.59	gold quality
right adrenal gland	UBERON:0001233	67.00	gold quality
left coronary artery	UBERON:0001626	66.86	gold quality
left adrenal gland cortex	UBERON:0035825	66.29	gold quality
left adrenal gland	UBERON:0001234	65.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.07	gold quality
spleen	UBERON:0002106	64.84	gold quality
cerebellum	UBERON:0002037	64.74	gold quality
cerebellar hemisphere	UBERON:0002245	64.71	gold quality
cerebellar cortex	UBERON:0002129	64.66	gold quality
adrenal gland	UBERON:0002369	64.45	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	26.40
E-GEOD-70580	no	15.92
E-ANND-3	no	2.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting CLEC18A, 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-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-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-6851-3P	95.73	65.11	688
HSA-MIR-3619-3P	95.59	65.99	428
HSA-MIR-328-3P	92.82	64.37	521

Literature-anchored findings (GeneRIF, showing 5)

• The human C-type lectin 18 (clec18) gene cluster, which contains three clec18a, clec18b, and clec18c loci, is located in human chromosome 16q22. (PMID:26170455)
• Plasma CLEC18 levels were correlated with the stage of HBV infection and could predict HBeAg loss and seroconversion in the patients with chronic hepatitis B (CHB) undergoing NUC therapy (PMID:30055605)
• High CLEC18 serum levels were associated with chronic HCV infection in rheumatic diseases. (PMID:30470801)
• Endosomal TLR3 co-receptor CLEC18A enhances host immune response to viral infection. (PMID:33603190)
• Human rs75776403 polymorphism links differential phenotypic and clinical outcomes to a CLEC18A p.T151M-driven multiomics. (PMID:35717171)

Cross-species orthologs

46 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clec18a	ENSMUSG00000033633
rattus_norvegicus	Clec18a	ENSRNOG00000022721
drosophila_melanogaster	Ag5r	FBGN0015010
drosophila_melanogaster	Ag5r2	FBGN0020508
drosophila_melanogaster	CG9400	FBGN0030562
drosophila_melanogaster	CG10651	FBGN0032853
drosophila_melanogaster	CG9822	FBGN0034623
drosophila_melanogaster	CG17974	FBGN0034624
drosophila_melanogaster	CG3640	FBGN0035042
drosophila_melanogaster	CG8072	FBGN0036070
drosophila_melanogaster	CG6628	FBGN0036072
drosophila_melanogaster	scpr-C	FBGN0037879
drosophila_melanogaster	scpr-B	FBGN0037888
drosophila_melanogaster	scpr-A	FBGN0037889
drosophila_melanogaster	CG8483	FBGN0038126
drosophila_melanogaster	CG30486	FBGN0050486
drosophila_melanogaster	antr	FBGN0050488
drosophila_melanogaster	CG31286	FBGN0051286
drosophila_melanogaster	CG32313	FBGN0052313
drosophila_melanogaster	CG32679	FBGN0052679
drosophila_melanogaster	CG34002	FBGN0054002
drosophila_melanogaster	CG17575	FBGN0250842
drosophila_melanogaster	CG42564	FBGN0260766
drosophila_melanogaster	CG42780	FBGN0261848
drosophila_melanogaster	CG43775	FBGN0264297
drosophila_melanogaster	CG43776	FBGN0264298
drosophila_melanogaster	CG43777	FBGN0264299
caenorhabditis_elegans		WBGENE00004742
caenorhabditis_elegans		WBGENE00007397
caenorhabditis_elegans		WBGENE00008027
caenorhabditis_elegans		WBGENE00008028
caenorhabditis_elegans		WBGENE00008029
caenorhabditis_elegans		WBGENE00008030
caenorhabditis_elegans		WBGENE00008625
caenorhabditis_elegans		WBGENE00009891
caenorhabditis_elegans		WBGENE00009895
caenorhabditis_elegans		WBGENE00009896
caenorhabditis_elegans		WBGENE00012816
caenorhabditis_elegans		WBGENE00013971
caenorhabditis_elegans		WBGENE00013972
caenorhabditis_elegans		WBGENE00015246
caenorhabditis_elegans		WBGENE00017055
caenorhabditis_elegans		WBGENE00017183
caenorhabditis_elegans		WBGENE00019178
caenorhabditis_elegans		WBGENE00019179
caenorhabditis_elegans		WBGENE00021780

Paralogs (13): CRISP3 (ENSG00000096006), R3HDML (ENSG00000101074), CRISPLD2 (ENSG00000103196), CRISPLD1 (ENSG00000121005), GLIPR2 (ENSG00000122694), CRISP2 (ENSG00000124490), CRISP1 (ENSG00000124812), PI15 (ENSG00000137558), GLIPR1 (ENSG00000139278), CLEC18B (ENSG00000140839), CLEC18C (ENSG00000157335), GLIPR1L1 (ENSG00000173401), GLIPR1L2 (ENSG00000180481)

Protein

Protein identifiers

C-type lectin domain family 18 member A — A5D8T8 (reviewed: A5D8T8)

Alternative names: Mannose receptor-like protein 2

All UniProt accessions (3): A5D8T8, F8W692, H3BNR9

UniProt curated annotations — full annotation on UniProt →

Function. Binds polysaccharides in a Ca(2+)-independent manner with a preferentially binding to fucoidan, beta-glucans and galactans.

Subcellular location. Secreted. Endoplasmic reticulum. Golgi apparatus. Endosome.

Tissue specificity. Dectected in all cell lines tested and in peripheral blood cells.

Post-translational modifications. N-glycosylated.

Isoforms (2)

UniProt ID	Names	Canonical?
A5D8T8-1	1	yes
A5D8T8-2	2

RefSeq proteins (4): NP_001129686, NP_001258126, NP_001357452, NP_872425 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR001283	CRISP-related	Family
IPR001304	C-type_lectin-like	Domain
IPR014044	CAP_dom	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR018378	C-type_lectin_CS	Conserved_site
IPR035940	CAP_sf	Homologous_superfamily

Pfam: PF00059, PF00188

UniProt features (19 total): disulfide bond 4, sequence variant 3, sequence conflict 3, domain 3, splice variant 2, signal peptide 1, chain 1, mutagenesis site 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5D8T8-F1	79.11	0.40

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 (4): 236–249, 251–260, 327–432, 408–424

Glycosylation sites (1): 144

Mutagenesis-validated functional residues (1):

Position	Phenotype
421	has a mild effect on polysaccharides binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 19 (showing top): chr16q22, GOMF_POLYSACCHARIDE_BINDING, MIR1827, GSE11864_UNTREATED_VS_CSF1_IFNG_PAM3CYS_IN_MAC_DN, GSE14026_TH1_VS_TH17_UP, GSE10147_IL3_AND_HIVP17_VS_IL3_AND_CPG_STIM_PDC_UP, ZHANG_FH_DEFICIENT_RCC_TUMOR_VS_NORMAL_DN, GOCC_ENDOSOME, NABA_ECM_AFFILIATED, NABA_MATRISOME_ASSOCIATED, NABA_MATRISOME, GSE2935_UV_INACTIVATED_VS_LIVE_SENDAI_VIRUS_INF_MACROPHAGE_UP, GSE3565_DUSP1_VS_WT_SPLENOCYTES_POST_LPS_INJECTION_DN, GSE4984_GALECTIN1_VS_VEHICLE_CTRL_TREATED_DC_DN, GSE21546_UNSTIM_VS_ANTI_CD3_STIM_ELK1_KO_DP_THYMOCYTES_UP

GO Biological Process (0):

GO Molecular Function (3): polysaccharide binding (GO:0030247), protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (5): obsolete extracellular space (GO:0005615), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
binding	2
cytoplasm	2
intracellular membrane-bounded organelle	2
carbohydrate binding	1
cytoplasmic vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC18A	LMNTD2	Q8IXW0	390
CLEC18A	ZSCAN25	Q6NSZ9	355
CLEC18A	SSC4D	Q8WTU2	342
CLEC18A	DPY19L4	Q7Z388	326
CLEC18A	LRRC37B	Q96QE4	322
CLEC18A	ZFAND1	Q8TCF1	311
CLEC18A	SP5	Q6BEB4	305
CLEC18A	MAST2	Q6P0Q8	284
CLEC18A	NPIPB11	E5RHQ5	271
CLEC18A	SPAG8	Q99932	269
CLEC18A	GPR137	Q96N19	263
CLEC18A	PLEKHG6	Q3KR16	262
CLEC18A	TTC39C	Q8N584	258
CLEC18A	ZMAT1	Q5H9K5	249
CLEC18A	OLFML2A	Q68BL7	248

IntAct

25 interactions, top by confidence:

A	B	Type	Score
CLEC18A	KRT40	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	CLEC18A	psi-mi:“MI:0915”(physical association)	0.560
CLEC18A	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
CLEC18A	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
CLEC18A	CYSRT1	psi-mi:“MI:0915”(physical association)	0.560
CLEC18A	KRT34	psi-mi:“MI:0915”(physical association)	0.560
CLEC18A	KRT31	psi-mi:“MI:0915”(physical association)	0.560
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
CLEC18A	HSPA5	psi-mi:“MI:0914”(association)	0.530
CLEC18A	APLP2	psi-mi:“MI:0915”(physical association)	0.400
CLEC18A	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
CLEC18A	KRT34	psi-mi:“MI:0915”(physical association)	0.000
CLEC18A	KRT31	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): CLEC18A (Two-hybrid), CLEC18A (Two-hybrid), NOTCH2NL (Two-hybrid), CLEC18A (Affinity Capture-MS), DNAJC3 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), SCRIB (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), MANBA (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), PDP1 (Affinity Capture-MS), CLEC18A (Affinity Capture-MS), SCRIB (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS)

ESM2 similar proteins: A5D8T8, O35217, O75078, O75882, O75900, O88272, O88507, O88676, O95633, P08887, P0C7M8, P0C7M9, P26992, P78539, Q00961, Q01098, Q08406, Q0ZCA7, Q14957, Q1LZB9, Q2TBM7, Q4V7F2, Q5EA46, Q5VV63, Q63769, Q642A6, Q6A051, Q6IA17, Q6P1D5, Q6PCB0, Q6UXF7, Q71DR4, Q7TNS7, Q7TSQ1, Q8NCF0, Q8R2Z5, Q8R366, Q91XD7, Q96FT7, Q96HD1

Diamond homologs: A0A218QX58, A1BQQ5, A5D8T8, A6YPK1, A8S6B6, B0VXV6, B2MVK7, B7FDI0, B7FDI1, C0ITL3, D4P2Y4, D8VNS1, F7C0L1, F8J2D4, G3CJR9, O19010, P0DMB9, P0DMT4, P0DPU0, P0DSI3, P10736, P10737, P11670, P16562, P16563, P35759, P35778, P35779, P35780, P35781, P35782, P35783, P35785, P35786, P35787, P36110, P47032, P54108, P60623, P79845

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	66
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2685575	GRCh37/hg19 16q22.1-22.3(chr16:69709450-73535741)x1	Pathogenic

SpliceAI

2228 predictions. Top by Δscore:

Variant	Effect	Δscore
16:69952032:CA:C	acceptor_loss	1.0000
16:69952033:A:AG	acceptor_gain	1.0000
16:69952034:G:GG	acceptor_gain	1.0000
16:69952122:GGCTG:G	donor_gain	1.0000
16:69952123:GCTG:G	donor_gain	1.0000
16:69952123:GCTGG:G	donor_gain	1.0000
16:69952125:TGGTG:T	donor_loss	1.0000
16:69952126:GGT:G	donor_loss	1.0000
16:69952127:G:GC	donor_loss	1.0000
16:69952127:G:GG	donor_gain	1.0000
16:69952128:TGA:T	donor_loss	1.0000
16:69952129:GA:G	donor_loss	1.0000
16:69952130:AGTA:A	donor_loss	1.0000
16:69961650:T:TA	acceptor_gain	1.0000
16:69961980:C:CA	acceptor_gain	1.0000
16:69962082:CGG:C	donor_gain	1.0000
16:69962083:GG:G	donor_gain	1.0000
16:69962083:GGG:G	donor_gain	1.0000
16:69962083:GGGTA:G	donor_loss	1.0000
16:69962084:GG:G	donor_gain	1.0000
16:69962084:GGT:G	donor_loss	1.0000
16:69962085:GT:G	donor_loss	1.0000
16:69962086:T:A	donor_loss	1.0000
16:69962952:T:TA	acceptor_gain	1.0000
16:69962962:ACCAT:A	acceptor_gain	1.0000
16:69962965:AT:A	acceptor_gain	1.0000
16:69962965:ATG:A	acceptor_gain	1.0000
16:69962966:T:G	acceptor_gain	1.0000
16:69962973:CAG:C	acceptor_loss	1.0000
16:69962974:AGGT:A	acceptor_loss	1.0000

AlphaMissense

2923 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:69963021:G:C	W419C	0.982
16:69963021:G:T	W419C	0.982
16:69962056:T:C	F395L	0.974
16:69962058:T:A	F395L	0.974
16:69962058:T:G	F395L	0.974
16:69963034:T:A	C424S	0.969
16:69963035:G:C	C424S	0.969
16:69962986:T:A	C408S	0.963
16:69962987:G:C	C408S	0.963
16:69963019:T:A	W419R	0.963
16:69963019:T:C	W419R	0.963
16:69961711:G:C	W370C	0.962
16:69961711:G:T	W370C	0.962
16:69962025:G:C	W384C	0.960
16:69962025:G:T	W384C	0.960
16:69962017:T:C	F382L	0.959
16:69962019:C:A	F382L	0.959
16:69962019:C:G	F382L	0.959
16:69960946:T:A	C327S	0.958
16:69960947:G:C	C327S	0.958
16:69962977:T:C	F405L	0.958
16:69962979:T:A	F405L	0.958
16:69962979:T:G	F405L	0.958
16:69962047:T:C	F392L	0.956
16:69962049:C:A	F392L	0.956
16:69962049:C:G	F392L	0.956
16:69963064:T:C	F434L	0.956
16:69963066:T:A	F434L	0.956
16:69963066:T:G	F434L	0.956
16:69962987:G:A	C408Y	0.955

dbSNP variants (sampled 300 via entrez): RS1000179532 (16:69943177 TCCTC>T), RS1000570275 (16:69952801 C>T), RS1001195522 (16:69965350 T>C,G), RS1001995751 (16:69966531 C>T), RS1002009958 (16:69950434 G>A), RS1002119415 (16:69952361 G>A,T), RS1002145680 (16:69951451 T>A,C), RS1002451166 (16:69966998 T>C,G), RS1002749333 (16:69942556 G>A,C), RS1003048671 (16:69964645 G>A,C), RS1003121054 (16:69948516 C>A), RS1003147585 (16:69947458 C>T), RS1003404804 (16:69964353 A>G), RS1004361658 (16:69962635 G>A,T), RS1004500500 (16:69963766 G>A)

Disease associations

OMIM: gene MIM:616571 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005951_13	Body mass index	5.000000e-11
GCST010703_100	Brain morphology (MOSTest)	2.000000e-40

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression, increases methylation	6
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
perfluorooctanoic acid	decreases expression, affects cotreatment	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	increases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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