CLEC14A

Summary

CLEC14A (C-type lectin domain containing 14A, HGNC:19832) is a protein-coding gene on chromosome 14q21.1, encoding C-type lectin domain family 14 member A (Q86T13).

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. This family member plays a role in cell-cell adhesion and angiogenesis. It functions in filopodia formation, cell migration and tube formation. Due to its presence at higher levels in tumor endothelium than in normal tissue endothelium, it is considered to be a candidate for tumor vascular targeting.

Source: NCBI Gene 161198 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 89 total — 3 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_175060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19832
Approved symbol	CLEC14A
Name	C-type lectin domain containing 14A
Location	14q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176435
Ensembl biotype	protein_coding
OMIM	616845
Entrez	161198

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000342213

RefSeq mRNA: 1 — MANE Select: NM_175060 NM_175060

CCDS: CCDS9667

Canonical transcript exons

ENST00000342213 — 1 exons

Exon	Start	End
ENSE00001374284	38254000	38256093

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 95.76.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3094 / max 239.6599, expressed in 383 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142998	2.5414	317
142997	1.6640	288
143000	0.5501	203
143001	0.3301	126
142995	0.0989	44
142996	0.0720	34
142999	0.0528	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.76	gold quality
right lung	UBERON:0002167	95.68	gold quality
vena cava	UBERON:0004087	95.40	gold quality
upper lobe of left lung	UBERON:0008952	94.83	gold quality
upper lobe of lung	UBERON:0008948	94.78	gold quality
upper arm skin	UBERON:0004263	94.69	gold quality
pericardium	UBERON:0002407	94.62	gold quality
urethra	UBERON:0000057	94.35	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.32	gold quality
lung	UBERON:0002048	93.16	gold quality
omental fat pad	UBERON:0010414	93.05	gold quality
left ventricle myocardium	UBERON:0006566	93.03	gold quality
peritoneum	UBERON:0002358	93.02	gold quality
tendon of biceps brachii	UBERON:0008188	92.77	gold quality
heart left ventricle	UBERON:0002084	92.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.70	gold quality
cardiac ventricle	UBERON:0002082	92.68	gold quality
lower lobe of lung	UBERON:0008949	92.40	gold quality
cardiac atrium	UBERON:0002081	92.10	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.09	gold quality
right atrium auricular region	UBERON:0006631	92.02	gold quality
cardia of stomach	UBERON:0001162	91.70	gold quality
adipose tissue	UBERON:0001013	91.56	gold quality
myocardium	UBERON:0002349	91.32	gold quality
heart	UBERON:0000948	91.19	gold quality
body of tongue	UBERON:0011876	90.37	gold quality
right lobe of thyroid gland	UBERON:0001119	90.32	gold quality
left uterine tube	UBERON:0001303	90.14	gold quality
body of uterus	UBERON:0009853	89.92	gold quality
kidney epithelium	UBERON:0004819	89.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	1747.73
E-MTAB-10553	yes	1042.74
E-MTAB-8381	yes	960.14
E-GEOD-135922	yes	780.32
E-MTAB-10287	yes	635.51
E-HCAD-1	yes	59.04
E-GEOD-134144	yes	55.80
E-HCAD-11	yes	51.01
E-MTAB-8410	yes	39.84
E-HCAD-10	yes	39.68
E-MTAB-6701	yes	36.91
E-CURD-46	yes	31.83
E-HCAD-9	yes	23.20
E-MTAB-6678	yes	14.10
E-CURD-112	yes	9.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting CLEC14A, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4731-3P	98.56	68.60	1860

Literature-anchored findings (GeneRIF, showing 12)

• In this study, they identify and characterize a novel tumor endothelial marker, CLEC14A, which has properties that suggest it is a candidate for tumor vascular targeting and anti-angiogenic approaches. (PMID:21706054)
• clec14a-CTLD may be a key domain in angiogenesis (PMID:23644659)
• CLEC14A is a matrix component which binds to MMRN2 in the process of endothelial cells transformation in tumor angiogenesis. (PMID:23979707)
• Results suggest that CLEC14A-MMRN2 binding has a role in inducing sprouting angiogenesis during tumor growth, which has the potential to be manipulated in future antiangiogenic therapy design. (PMID:25745997)
• The CLEC14A-MMRN2 interaction is involved in sprouting angiogenesis. Disrupting this interaction with monoclonal antibodies directed against CLEC14A show anti-angiogenic and anti-tumor effects. (PMID:25745997)
• These findings identify novel protein interactions involving CLEC14A, CD93 and CD248 with MMRN2 as targetable components of vessel formation (PMID:28671670)
• Activin receptor-like kinase 1 is associated with immune cell infiltration and regulates CLEC14A transcription in cancer. (PMID:30132150)
• CLEC14A acts as an antitumor role in lung adenocarcinoma (LUAD) by suppressing cell proliferation, migration, invasion, promoting cell apoptosis, and reducing tumorigenicity in nude mice. Thus, the inhibition of CLEC14A methylation is a novel strategy for the clinic treatment of LUAD (PMID:30191970)
• Study identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5 and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration. (PMID:31852888)
• Proteomics-based screening of the endothelial heparan sulfate interactome reveals that C-type lectin 14a (CLEC14A) is a heparin-binding protein. (PMID:31964714)
• An evaluation of the tumour endothelial marker CLEC14A as a therapeutic target in solid tumours. (PMID:32696621)
• CLEC14A was up-regulated in hepatocellular carcinoma and may function as a potential diagnostic biomarker. (PMID:35576868)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clec14a	ENSMUSG00000045930
rattus_norvegicus	Clec14a	ENSRNOG00000022697
caenorhabditis_elegans		WBGENE00000168
caenorhabditis_elegans		WBGENE00012018
caenorhabditis_elegans		WBGENE00013480
caenorhabditis_elegans		WBGENE00013486
caenorhabditis_elegans		WBGENE00013487
caenorhabditis_elegans		WBGENE00018906
caenorhabditis_elegans		WBGENE00019901
caenorhabditis_elegans		WBGENE00022858

Paralogs (8): DLL3 (ENSG00000090932), CD93 (ENSG00000125810), FBLN7 (ENSG00000144152), WIF1 (ENSG00000156076), CRELD1 (ENSG00000163703), DLK2 (ENSG00000171462), CD248 (ENSG00000174807), CRELD2 (ENSG00000184164)

Protein

Protein identifiers

C-type lectin domain family 14 member A — Q86T13 (reviewed: Q86T13)

Alternative names: Epidermal growth factor receptor 5

All UniProt accessions (1): Q86T13

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_778230* (*=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
IPR051505	C-type_lectin_domain	Family

UniProt features (15 total): glycosylation site 2, sequence conflict 2, topological domain 2, domain 2, region of interest 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86T13-F1	69.00	0.44

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 (1): 143–162

Glycosylation sites (2): 189, 381

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, AP4_Q6, CAGCTG_AP4_Q5, GOBP_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_SPROUTING_ANGIOGENESIS, MYOD_01, GOBP_BLOOD_VESSEL_MORPHOGENESIS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_LYMPH_VESSEL_MORPHOGENESIS, RYTTCCTG_ETS2_B, CUI_TCF21_TARGETS_2_DN

GO Biological Process (6): lymphangiogenesis (GO:0001946), cell migration involved in sprouting angiogenesis (GO:0002042), cell migration (GO:0016477), vascular endothelial growth factor receptor-2 signaling pathway (GO:0036324), vascular endothelial growth factor receptor-3 signaling pathway (GO:0036325), sprouting angiogenesis (GO:0002040)

GO Molecular Function (4): carbohydrate binding (GO:0030246), extracellular matrix binding (GO:0050840), extracellular matrix protein binding (GO:1990430), protein binding (GO:0005515)

GO Cellular Component (3): external side of plasma membrane (GO:0009897), extracellular matrix (GO:0031012), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
vascular endothelial growth factor receptor signaling pathway	2
anatomical structure morphogenesis	1
lymph vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
cell motility	1
angiogenesis	1
protein binding	1
plasma membrane	1
cell surface	1
side of membrane	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC14A	RNGTT	O60942	928
CLEC14A	MMRN2	Q9H8L6	864
CLEC14A	RNMT	O43148	813
CLEC14A	CES1	P23141	776
CLEC14A	FLT4	P35916	545
CLEC14A	ETV2	O00321	500
CLEC14A	EGF	P01133	474
CLEC14A	RHBDL2	Q9NX52	455
CLEC14A	PCNX1	Q96RV3	426
CLEC14A	MLF2	Q15773	422
CLEC14A	ROBO4	Q8WZ75	421
CLEC14A	RHBDL1	O75783	415
CLEC14A	ALLC	Q8N6M5	393
CLEC14A	POLR2A	P24928	387
CLEC14A	PREB	Q9HCU5	377

IntAct

56 interactions, top by confidence:

A	B	Type	Score
	CLEC14A	psi-mi:“MI:0407”(direct interaction)	0.690
TSPAN2	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
EMD	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0C	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
CYB561D2	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
CLEC14A	CLDN19	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
CLEC14A	MGST2	psi-mi:“MI:0915”(physical association)	0.560
MALL	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
PMP22	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
CLEC14A	TMEM243	psi-mi:“MI:0915”(physical association)	0.560
MS4A1	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
CLEC14A	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
CLDN4	CLEC14A	psi-mi:“MI:0915”(physical association)	0.560
	CLEC14A	psi-mi:“MI:0407”(direct interaction)	0.560
	CLEC14A	psi-mi:“MI:0407”(direct interaction)	0.440
CLEC14A	CLEC14A	psi-mi:“MI:0407”(direct interaction)	0.440
CLEC14A	PXK	psi-mi:“MI:0914”(association)	0.350
	CCN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (90): TMEM159 (Affinity Capture-MS), PXK (Affinity Capture-MS), INTS7 (Affinity Capture-MS), PTCD2 (Affinity Capture-MS), FAM115A (Affinity Capture-MS), MMRN2 (Affinity Capture-MS), LAMA4 (Affinity Capture-MS), PRRC2A (Affinity Capture-MS), FMR1 (Affinity Capture-MS), FXR2 (Affinity Capture-MS), FXR1 (Affinity Capture-MS), TBK1 (Affinity Capture-MS), IGF2BP1 (Affinity Capture-MS), IGF2BP3 (Affinity Capture-MS), PABPC4 (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, A6QNY1, D3YZF7, O95428, P28698, P30203, P55068, P55106, P59222, P98162, Q04756, Q14767, Q28019, Q28062, Q28256, Q28343, Q28670, Q3U515, Q4G0T1, Q5F378, Q5HZW5, Q61003, Q61361, Q6H9L7, Q6KF10, Q6PGE4, Q6QNF4, Q7TQH7, Q7Z4F1, Q86T13, Q86VR7, Q86VZ4, Q8BV57, Q8BZE1, Q8CB67, Q8VCP9, Q8WTU2, Q91V98, Q96DN2

Diamond homologs: Q86T13, Q8VCP9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	79
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1527809	GRCh37/hg19 14q13.3-21.1(chr14:36862276-41597549)	Pathogenic
57775	GRCh38/hg38 14q13.3-21.1(chr14:36434568-41102476)x1	Pathogenic
815639	GRCh37/hg19 14q13.3-21.1(chr14:36830396-42541277)x1	Pathogenic
149764	GRCh38/hg38 14q21.1(chr14:37533702-38648187)x1	Likely pathogenic

SpliceAI

41 predictions. Top by Δscore:

Variant	Effect	Δscore
14:38255510:G:A	donor_gain	0.9100
14:38255509:TGC:T	donor_gain	0.9000
14:38255508:TTG:T	donor_gain	0.7800
14:38255502:TGG:T	donor_gain	0.5700
14:38255386:TCA:T	donor_loss	0.4900
14:38255387:CA:C	donor_loss	0.4900
14:38255388:A:AG	donor_loss	0.4900
14:38254989:T:TG	acceptor_gain	0.4800
14:38255506:A:AC	donor_gain	0.4700
14:38255507:C:CC	donor_gain	0.4700
14:38254860:GTGGC:G	acceptor_gain	0.4300
14:38255508:T:C	donor_gain	0.4300
14:38255279:C:G	acceptor_gain	0.4200
14:38255431:G:C	acceptor_gain	0.4100
14:38255278:TCCC:T	acceptor_gain	0.3900
14:38255389:CCT:C	donor_gain	0.3400
14:38255388:A:AC	donor_gain	0.3300
14:38255389:C:CC	donor_gain	0.3300
14:38255390:C:G	donor_loss	0.3100
14:38254862:GGC:G	acceptor_gain	0.3000
14:38255386:TCAC:T	acceptor_gain	0.2800
14:38255387:CACC:C	acceptor_gain	0.2800
14:38254848:AAAG:A	acceptor_gain	0.2700
14:38255382:GCAC:G	acceptor_gain	0.2700
14:38254990:C:G	acceptor_gain	0.2600
14:38255152:C:A	donor_gain	0.2600
14:38255383:CACT:C	acceptor_gain	0.2600
14:38255384:ACTC:A	acceptor_gain	0.2500
14:38255388:ACC:A	acceptor_gain	0.2500
14:38254863:GC:G	acceptor_gain	0.2400

AlphaMissense

3134 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:38255633:C:A	W130C	0.999
14:38255633:C:G	W130C	0.999
14:38255318:C:A	W235C	0.997
14:38255318:C:G	W235C	0.997
14:38255684:G:C	F113L	0.996
14:38255684:G:T	F113L	0.996
14:38255686:A:G	F113L	0.996
14:38255511:C:G	C171S	0.995
14:38255512:A:T	C171S	0.995
14:38255685:A:C	F113C	0.995
14:38255744:C:A	W93C	0.994
14:38255744:C:G	W93C	0.994
14:38255635:A:G	W130R	0.992
14:38255635:A:T	W130R	0.992
14:38255511:C:T	C171Y	0.991
14:38255552:C:A	W157C	0.991
14:38255552:C:G	W157C	0.991
14:38255862:C:T	C54Y	0.991
14:38255906:G:C	S39R	0.990
14:38255906:G:T	S39R	0.990
14:38255908:T:G	S39R	0.990
14:38255345:G:C	C226W	0.989
14:38255685:A:G	F113S	0.989
14:38255861:G:C	C54W	0.989
14:38255505:T:C	Y173C	0.988
14:38255510:G:C	C171W	0.988
14:38255862:C:G	C54S	0.987
14:38255863:A:T	C54S	0.987
14:38255346:C:G	C226S	0.986
14:38255346:C:T	C226Y	0.986

dbSNP variants (sampled 300 via entrez): RS1000613300 (14:38256467 G>A), RS1002862941 (14:38256010 A>G), RS1003004217 (14:38254908 G>C,T), RS1003512102 (14:38255762 G>A), RS1006053713 (14:38255093 T>G), RS1006134019 (14:38254737 G>C), RS1006398280 (14:38257597 T>C,G), RS1007005060 (14:38254248 A>G), RS1007348317 (14:38255391 T>A,G), RS1008624220 (14:38255527 C>A,T), RS1009956918 (14:38254634 C>A,T), RS1010243048 (14:38257129 T>G), RS1010556157 (14:38256743 T>A,C), RS1010621254 (14:38257481 C>G,T), RS1010691979 (14:38257074 C>G)

Disease associations

OMIM: gene MIM:616845 | 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
GCST001821_11	Metabolite levels (5-HIAA/ MHPG Ratio)	5.000000e-08
GCST004125_20	Type 2 diabetes (age of onset)	8.000000e-06
GCST004125_23	Type 2 diabetes (age of onset)	3.000000e-06
GCST004125_26	Type 2 diabetes (age of onset)	9.000000e-06
GCST009379_193	Type 2 diabetes	2.000000e-08
GCST010118_97	Type 2 diabetes	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005132	5-HIAA measurement
EFO:0005133	MHPG measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
cobaltous chloride	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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