CLEC3B

Summary

CLEC3B (C-type lectin domain family 3 member B, HGNC:11891) is a protein-coding gene on chromosome 3p21.31, encoding Tetranectin (P05452). Tetranectin binds to plasminogen and to isolated kringle 4.

Enables calcium ion binding activity; heparin binding activity; and kringle domain binding activity. Involved in bone mineralization. Located in cytoplasm; extracellular space; and granular component. Implicated in osteoarthritis and retinal macular dystrophy 4.

Source: NCBI Gene 7123 — RefSeq curated summary.

At a glance

• Gene–disease (curated): macular dystrophy, retinal, 4 (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 28 total — 1 pathogenic
• Phenotypes (HPO): 7
• MANE Select transcript: NM_003278

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11891
Approved symbol	CLEC3B
Name	C-type lectin domain family 3 member B
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	TN
Ensembl gene	ENSG00000163815
Ensembl biotype	protein_coding
OMIM	187520
Entrez	7123

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000296130, ENST00000428034, ENST00000490386, ENST00000872072

RefSeq mRNA: 2 — MANE Select: NM_003278 NM_001308394, NM_003278

CCDS: CCDS2726, CCDS77730

Canonical transcript exons

ENST00000296130 — 3 exons

Exon	Start	End
ENSE00001281126	45026303	45026471
ENSE00003500005	45030827	45030925
ENSE00003628193	45035524	45036071

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 99.13.

FANTOM5 (CAGE): breadth broad, TPM avg 40.3179 / max 3575.8050, expressed in 638 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36362	25.9327	517
36361	11.8062	572
36363	1.3361	272
36360	0.7011	211
36358	0.2468	108
36359	0.1421	73
36357	0.1217	56
36364	0.0291	3
202739	0.0021	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
subcutaneous adipose tissue	UBERON:0002190	99.13	gold quality
apex of heart	UBERON:0002098	98.65	gold quality
right atrium auricular region	UBERON:0006631	98.61	gold quality
adipose tissue	UBERON:0001013	98.38	gold quality
tibial nerve	UBERON:0001323	98.37	gold quality
right lung	UBERON:0002167	98.36	gold quality
placenta	UBERON:0001987	98.25	gold quality
spleen	UBERON:0002106	98.13	gold quality
right testis	UBERON:0004534	97.64	gold quality
right coronary artery	UBERON:0001625	97.49	gold quality
omental fat pad	UBERON:0010414	97.49	gold quality
upper lobe of left lung	UBERON:0008952	97.28	gold quality
heart left ventricle	UBERON:0002084	97.23	gold quality
left testis	UBERON:0004533	97.14	gold quality
testis	UBERON:0000473	97.11	gold quality
thoracic mammary gland	UBERON:0005200	96.89	gold quality
heart	UBERON:0000948	96.88	gold quality
calcaneal tendon	UBERON:0003701	96.85	gold quality
skin of leg	UBERON:0001511	96.75	gold quality
descending thoracic aorta	UBERON:0002345	96.61	gold quality
metanephros cortex	UBERON:0010533	96.42	gold quality
zone of skin	UBERON:0000014	96.40	gold quality
lung	UBERON:0002048	96.36	gold quality
skin of abdomen	UBERON:0001416	96.27	gold quality
adult mammalian kidney	UBERON:0000082	96.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.42	gold quality
left coronary artery	UBERON:0001626	95.35	gold quality
lower esophagus	UBERON:0013473	95.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	2131.61
E-GEOD-135922	yes	743.48
E-MTAB-10553	yes	56.98
E-CURD-46	yes	27.93
E-HCAD-9	yes	22.73
E-ANND-3	yes	14.24
E-CURD-112	yes	6.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting CLEC3B, 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-548AW	99.99	72.57	3559
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126

Literature-anchored findings (GeneRIF, showing 14)

• analyze the immunohistochemical localization of tetranectin in gastric adenocarcinomas and the adjacent tissues of the wall of the stomach (PMID:11962752)
• Tetranectin may play an important role in the survival of islets in the liver after islet transplantation. (PMID:15848710)
• results predict that a positive TN expression of both tumour tissue and serum points to a more favourable outcome for ovarian cancer patients (PMID:25846370)
• study suggests that increased serum TN level is associated with the presence and severity of diseased coronary arteries in patients with stable CAD. (PMID:26621497)
• The present study identified the CLEC3B p.S106G as a novel longevity-associated variant, raising the novel hypothesis that tetranectin, encoded by CLEC3B, plays a role in human longevity and aging (PMID:27154906)
• TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients’ outcomes and survival (PMID:28718365)
• Integrative epigenomics, transcriptomics and proteomics of patients chondrocytes from hip or knee osteoarthritis (OA) identified AQP1, COL1A1 and CLEC3B as significantly and differentially regulated suggesting they play an important role in OA pathogenesis. (PMID:28827734)
• Low CLEC3B expression is associated with clear cell renal cell carcinoma. (PMID:30066941)
• The In Vitro Biotransformation of the Fusion Protein Tetranectin-Apolipoprotein A1. (PMID:30858459)
• CLEC3B acts as a novel independent prognostic factor (PMID:31477130)
• CLEC3B p.S106G Mutant in a Caucasian Population of Successful Neurological Aging. (PMID:31570938)
• CLEC3B alleviated the injury of hypoxic H9c2 cardiomyocytes via the PI3K/Akt pathway (PMID:32696821)
• Down-regulation of CLEC3B facilitates epithelial-mesenchymal transition, migration and invasion of lung adenocarcinoma cells. (PMID:35500520)
• Tetranectin as a potential novel prognostic biomarker in anthracycline-related cardiac dysfunction. (PMID:37310463)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	clec3ba	ENSDARG00000076541
danio_rerio	clec3bb	ENSDARG00000099500
mus_musculus	Clec3b	ENSMUSG00000025784

Paralogs (2): CLEC11A (ENSG00000105472), CLEC3A (ENSG00000166509)

Protein

Protein identifiers

Tetranectin — P05452 (reviewed: P05452)

Alternative names: C-type lectin domain family 3 member B, Plasminogen kringle 4-binding protein

All UniProt accessions (2): E9PHK0, P05452

UniProt curated annotations — full annotation on UniProt →

Function. Tetranectin binds to plasminogen and to isolated kringle 4. May be involved in the packaging of molecules destined for exocytosis. Plays a role in retinal function.

Subunit / interactions. Homotrimer.

Subcellular location. Secreted.

Tissue specificity. Found in plasma.

Disease relevance. Macular dystrophy, retinal, 4 (MCDR4) [MIM:619977] An autosomal dominant retinal disease characterized by late-onset macular degeneration, with multiple drusen-like deposits, macular geographic atrophy, and choroidal neovascularization. Patients also exhibit extensive retinal dysfunction with impaired rod function. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001295323, NP_003269* (*=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
IPR051663	CLec_Tetranectin-domain	Family

Pfam: PF00059

UniProt features (27 total): strand 11, sequence variant 4, helix 3, disulfide bond 3, turn 2, signal peptide 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1TN3	X-RAY DIFFRACTION	2
3L9J	X-RAY DIFFRACTION	2.1
1HTN	X-RAY DIFFRACTION	2.8
1RJH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05452-F1	87.85	0.77

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 (3): 71–81, 98–197, 173–189

Glycosylation sites (1): 25

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 181 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, MODULE_66, GOBP_PROTEIN_MATURATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_BONE_MINERALIZATION, INGRAM_SHH_TARGETS_UP, MODULE_410, ONDER_CDH1_TARGETS_2_UP, GOBP_REGULATION_OF_PROTEIN_MATURATION

GO Biological Process (3): ossification (GO:0001503), positive regulation of plasminogen activation (GO:0010756), bone mineralization (GO:0030282)

GO Molecular Function (4): calcium ion binding (GO:0005509), heparin binding (GO:0008201), carbohydrate binding (GO:0030246), kringle domain binding (GO:0036143)

GO Cellular Component (7): granular component (GO:0001652), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular matrix (GO:0031012), platelet dense granule lumen (GO:0031089), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
multicellular organismal process	1
regulation of plasminogen activation	1
positive regulation of protein processing	1
plasminogen activation	1
ossification	1
biomineral tissue development	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1
protein domain specific binding	1
nucleolus	1
intracellular anatomical structure	1
external encapsulating structure	1
secretory granule lumen	1
platelet dense granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

1324 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC3B	PLG	P00747	997
CLEC3B	ENO1	P06733	762
CLEC3B	PLAT	P00750	559
CLEC3B	THBS1	P07996	557
CLEC3B	ALB	P02768	541
CLEC3B	SELENOP	P49908	536
CLEC3B	FCN3	O75636	534
CLEC3B	FN1	P02751	522
CLEC3B	PON1	P27169	509
CLEC3B	A2M	P01023	503
CLEC3B	ORM1	P02763	500
CLEC3B	HGF	P14210	475
CLEC3B	SMOC1	Q9H4F8	474
CLEC3B	CCBE1	Q6UXH8	459
CLEC3B	LAMA1	P25391	458

IntAct

24 interactions, top by confidence:

A	B	Type	Score
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
	LECT2	psi-mi:“MI:0915”(physical association)	0.400
CLEC3B	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
CLEC3B	CDKN1A	psi-mi:“MI:0915”(physical association)	0.370
GADD45A	CLEC3B	psi-mi:“MI:0915”(physical association)	0.370
GSK3B	CLEC3B	psi-mi:“MI:0915”(physical association)	0.370
CLEC3B	RPS6KA6	psi-mi:“MI:0915”(physical association)	0.370
CLEC3B	RPS6KB1	psi-mi:“MI:0915”(physical association)	0.370
CLEC3B	SH3GL2	psi-mi:“MI:0915”(physical association)	0.370
TK1	CLEC3B	psi-mi:“MI:0915”(physical association)	0.370
STAT3	IDH3B	psi-mi:“MI:0914”(association)	0.350
ATF2	ABLIM1	psi-mi:“MI:0914”(association)	0.350
MYB	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
STAT3	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
CEBPA	HAX1	psi-mi:“MI:0914”(association)	0.350
STAT3	HAX1	psi-mi:“MI:0914”(association)	0.350
CLEC3B	OSTF1	psi-mi:“MI:0915”(physical association)	0.000
FGF13	CLEC3B	psi-mi:“MI:0915”(physical association)	0.000
OTUD4	CLEC3B	psi-mi:“MI:0915”(physical association)	0.000
CLEC3B	THRAP3	psi-mi:“MI:0915”(physical association)	0.000
CLEC3B	KRT18	psi-mi:“MI:0915”(physical association)	0.000
FMR1	CLEC3B	psi-mi:“MI:0915”(physical association)	0.000
DISC1	CLEC3B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): OSTF1 (Affinity Capture-MS), KRT18 (Affinity Capture-MS), OTUD4 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), PLAT (Reconstituted Complex), HGF (Reconstituted Complex), CLEC3B (Negative Genetic), CLEC3B (Affinity Capture-MS), CLEC3B (Affinity Capture-MS), CLEC3B (Two-hybrid), CLEC3B (Two-hybrid), CLEC3B (Two-hybrid), CLEC3B (Two-hybrid), CLEC3B (Two-hybrid), CLEC3B (Two-hybrid)

ESM2 similar proteins: A0A1D5PUP4, O60242, O75882, O95970, P05452, P07306, P09858, P0C7M9, P15209, P21214, P24786, P25291, P27090, P37173, P43025, P51641, P61811, P61812, P78539, Q0ZCA7, Q1EGL2, Q2KIS7, Q2LK94, Q38L25, Q3SXB8, Q4TU93, Q5R7T2, Q5R945, Q5RBQ8, Q5RKH0, Q5VV63, Q62312, Q63604, Q63769, Q64449, Q6A051, Q6UXF7, Q6UXS0, Q80ZF8, Q8N475

Diamond homologs: O02659, O75596, O88201, P05452, P11226, P19999, P23805, P26258, P35247, P35248, P41317, P43025, P50404, P60883, P82596, P86854, P98106, P98109, Q01102, Q1PBC5, Q28008, Q2KIS7, Q5MIZ0, Q5U3G1, Q5U9S1, Q61830, Q66KU1, Q66S37, Q66S41, Q66S45, Q66S50, Q66S54, Q66S58, Q66S60, Q66S61, Q66S62, Q66S63, Q66S64, Q66S65, Q6ZS10

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of gene expression	5	13.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1698394	NM_003278.3(CLEC3B):c.539C>A (p.Ala180Asp)	Pathogenic

SpliceAI

968 predictions. Top by Δscore:

Variant	Effect	Δscore
3:45007504:G:GT	donor_gain	1.0000
3:45007525:A:T	donor_gain	1.0000
3:45007575:GGTGA:G	donor_loss	1.0000
3:45007576:GTGA:G	donor_loss	1.0000
3:45007577:T:G	donor_loss	1.0000
3:45026467:GAAAG:G	donor_gain	1.0000
3:45026469:AAGG:A	donor_loss	1.0000
3:45026471:GGTA:G	donor_loss	1.0000
3:45026472:G:C	donor_loss	1.0000
3:45035522:A:AG	acceptor_gain	1.0000
3:45035523:G:GA	acceptor_gain	1.0000
3:45035523:GTCT:G	acceptor_gain	1.0000
3:45001605:CAAGG:C	donor_loss	0.9900
3:45001607:AGG:A	donor_loss	0.9900
3:45001609:G:GG	donor_gain	0.9900
3:45001609:GTAA:G	donor_loss	0.9900
3:45001610:TAA:T	donor_loss	0.9900
3:45005286:TCCA:T	acceptor_loss	0.9900
3:45005289:A:AC	acceptor_loss	0.9900
3:45005289:A:AG	acceptor_gain	0.9900
3:45005289:AG:A	acceptor_gain	0.9900
3:45005290:G:GA	acceptor_gain	0.9900
3:45005290:GG:G	acceptor_gain	0.9900
3:45005411:CAAG:C	donor_gain	0.9900
3:45005411:CAAGG:C	donor_loss	0.9900
3:45005412:AAGG:A	donor_loss	0.9900
3:45005413:AGG:A	donor_loss	0.9900
3:45005415:GTAT:G	donor_loss	0.9900
3:45005416:T:G	donor_loss	0.9900
3:45007418:A:AG	acceptor_gain	0.9900

AlphaMissense

1321 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:45035608:G:A	C98Y	0.999
3:45035609:C:G	C98W	0.999
3:45035786:G:C	W157C	0.999
3:45035786:G:T	W157C	0.999
3:45035556:T:A	C81S	0.998
3:45035556:T:C	C81R	0.998
3:45035557:G:C	C81S	0.998
3:45035595:G:C	A94P	0.998
3:45035784:T:A	W157R	0.998
3:45035784:T:C	W157R	0.998
3:45035865:T:A	W184R	0.998
3:45035865:T:C	W184R	0.998
3:45035867:G:C	W184C	0.998
3:45035867:G:T	W184C	0.998
3:45035526:T:A	C71S	0.997
3:45035526:T:C	C71R	0.997
3:45035527:G:C	C71S	0.997
3:45035558:C:G	C81W	0.997
3:45035607:T:A	C98S	0.997
3:45035607:T:C	C98R	0.997
3:45035608:G:C	C98S	0.997
3:45035608:G:T	C98F	0.997
3:45035747:G:C	W144C	0.997
3:45035747:G:T	W144C	0.997
3:45035832:T:A	C173S	0.997
3:45035832:T:C	C173R	0.997
3:45035833:G:C	C173S	0.997
3:45035834:C:G	C173W	0.997
3:45035904:T:A	C197S	0.997
3:45035905:G:A	C197Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000253223 (3:45030280 T>G), RS1000261759 (3:45025497 C>G,T), RS1000542915 (3:45031757 G>A,T), RS1000699496 (3:45025209 G>A), RS1001151025 (3:45030152 T>A), RS1001621755 (3:45030481 C>A,T), RS1001999330 (3:45035539 C>T), RS1002050223 (3:45031015 G>A), RS1002557542 (3:45028515 C>T), RS1003005980 (3:45033994 G>A), RS1004007787 (3:45034459 C>T), RS1004237690 (3:45025842 A>C,G), RS1004451906 (3:45032715 G>A), RS1004877 (3:45025925 G>A,C,T), RS1005010479 (3:45031246 G>A)

Disease associations

OMIM: gene MIM:187520 | disease phenotypes: MIM:619977

GenCC curated gene-disease

Disease	Classification	Inheritance
macular dystrophy, retinal, 4	Strong	Autosomal dominant

Mondo (1): macular dystrophy, retinal, 4 (MONDO:0859568)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000662	Nyctalopia
HP:0003584	Late onset
HP:0003596	Middle age onset
HP:0007663	Reduced visual acuity
HP:0011506	Choroidal neovascularization
HP:0030619	Reduced OCT-measured foveal thickness

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002481_7	Acne (severe)	3.000000e-06
GCST006585_1312	Blood protein levels	3.000000e-18
GCST012214_2	Alzheimer’s disease	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	3
Arsenic	decreases methylation, affects methylation	2
Calcitriol	decreases expression, decreases reaction, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
versicolorin A	increases expression	1
corosolic acid	increases expression	1
clothianidin	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Calcium Chloride	increases expression	1
Copper	affects binding	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Nickel	decreases expression	1
Oxygen	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Testosterone	affects cotreatment, decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cyclosporine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9WB	Ubigene HMC3 CLEC3B KO	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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