CLEC11A

Summary

CLEC11A (C-type lectin domain containing 11A, HGNC:10576) is a protein-coding gene on chromosome 19q13.33, encoding C-type lectin domain family 11 member A (Q9Y240). Promotes osteogenesis by stimulating the differentiation of mesenchymal progenitors into mature osteoblasts.

This gene encodes a member of the C-type lectin superfamily. The encoded protein is a secreted sulfated glycoprotein and functions as a growth factor for primitive hematopoietic progenitor cells. An alternative splice variant has been described but its biological nature has not been determined.

Source: NCBI Gene 6320 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_002975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10576
Approved symbol	CLEC11A
Name	C-type lectin domain containing 11A
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	P47, LSLCL, CLECSF3
Ensembl gene	ENSG00000105472
Ensembl biotype	protein_coding
OMIM	604713
Entrez	6320

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000250340, ENST00000599973, ENST00000883280, ENST00000883281, ENST00000883282

RefSeq mRNA: 1 — MANE Select: NM_002975 NM_002975

CCDS: CCDS12800

Canonical transcript exons

ENST00000250340 — 4 exons

Exon	Start	End
ENSE00000723360	50723905	50724091
ENSE00000888894	50723364	50723672
ENSE00001059712	50724410	50724601
ENSE00001116546	50725022	50725708

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7063 / max 919.8423, expressed in 1141 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177165	9.6922	956
177164	8.4041	894
177166	1.7590	408
177168	0.4894	328
177167	0.2475	41
208905	0.1142	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.82	gold quality
tibia	UBERON:0000979	97.40	gold quality
periodontal ligament	UBERON:0008266	97.01	gold quality
trabecular bone tissue	UBERON:0002483	91.63	gold quality
bone element	UBERON:0001474	90.50	gold quality
endocervix	UBERON:0000458	90.31	gold quality
bone marrow	UBERON:0002371	89.56	gold quality
right ovary	UBERON:0002118	89.24	gold quality
left uterine tube	UBERON:0001303	88.42	gold quality
left ovary	UBERON:0002119	88.01	gold quality
right uterine tube	UBERON:0001302	87.74	gold quality
ectocervix	UBERON:0012249	87.55	gold quality
body of uterus	UBERON:0009853	87.32	gold quality
metanephros cortex	UBERON:0010533	87.26	gold quality
adenohypophysis	UBERON:0002196	86.14	gold quality
bone marrow cell	CL:0002092	86.02	gold quality
left adrenal gland cortex	UBERON:0035825	84.92	gold quality
pituitary gland	UBERON:0000007	84.66	gold quality
cervix squamous epithelium	UBERON:0006922	84.66	silver quality
left adrenal gland	UBERON:0001234	84.48	gold quality
right adrenal gland	UBERON:0001233	84.41	gold quality
right adrenal gland cortex	UBERON:0035827	83.95	gold quality
endothelial cell	CL:0000115	83.82	gold quality
caput epididymis	UBERON:0004358	83.56	gold quality
ovary	UBERON:0000992	83.55	gold quality
vagina	UBERON:0000996	83.52	gold quality
omental fat pad	UBERON:0010414	83.41	gold quality
peritoneum	UBERON:0002358	83.34	gold quality
adrenal cortex	UBERON:0001235	83.33	gold quality
mucosa of stomach	UBERON:0001199	83.16	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	108.91
E-MTAB-8410	yes	52.48
E-HCAD-10	yes	45.15
E-HCAD-11	yes	44.01
E-MTAB-6075	yes	40.71
E-CURD-112	yes	40.09
E-HCAD-6	yes	38.45
E-MTAB-9067	yes	20.12
E-CURD-122	yes	15.36
E-ANND-3	yes	10.20
E-MTAB-10042	yes	8.98
E-MTAB-9801	yes	5.66
E-MTAB-10553	yes	5.06
E-MTAB-6142	no	9.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting CLEC11A, 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-3692-3P	99.98	70.27	2139
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-1204	89.50	65.56	109

Literature-anchored findings (GeneRIF, showing 13)

• SCGF is selectively produced by osseous and hematopoietic stromal cells, and can mediate their proliferative activity on primitive hematopoietic progenitor cells. (PMID:11920266)
• Results indicate that interleukin-4, together with recombinant human stem cell factor, can induce T cell maturation from cord blood progenitor cells, and that IL-4 increased the expression of FcepsilonRI on fetal liver mast cells. (PMID:14746805)
• Human vascular smooth muscle cells express stem cell factor(SCF) and its receptor, c-kit. SCF is released from its membrane-bound form via MMP-9. SCF/c-kit signaling may affect SMC function via an autocrine pathway. (PMID:15234225)
• phagocytosis of hemozoin promotes a decrease in SCGF gene products, which may contribute to reduced erythropoiesis in children with severe malarial anemia. (PMID:19528216)
• The results presented here demonstrate that homozygous T at -539 in the SCGF promoter is associated with elevated SCGF production, enhanced erythropoiesis, and protection against severe malarial anemia. (PMID:19884328)
• These studies highlight a possible role of SCGFalpha in imatinib-induced changes of gastrointestinal stromal tumors structure, consistent with a therapeutic response. (PMID:21943129)
• This is the first report of SCGF beta in heart failure patients. (PMID:23357302)
• level of expression correlates with pain response in subjects with intervertebral disc disorders (PMID:26440592)
• Data show that asymptomatic patients with unstable plaques exhibited higher levels of endothelial microparticles (EMPs), CXCL9 chemokine and stem cell growth factor; lymphocyte secreted C-type lectin (SCGF-beta) compared to those with stable plaques. (PMID:26564003)
• Clec11a maintains the adult skeleton by promoting the differentiation of mesenchymal progenitors into mature osteoblasts. (PMID:27976999)
• The effect of parathyroid hormone on osteogenesis is mediated partly by osteolectin. (PMID:34140410)
• Identification and characterization of CLEC11A and its derived immune signature in gastric cancer. (PMID:38348052)
• CLEC11A methylation is correlated to AML subtypes and cytogenetic risk factors but not patient demographics. (PMID:38466706)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	clec11a	ENSDARG00000079107
mus_musculus	Clec11a	ENSMUSG00000004473
rattus_norvegicus	Clec11a	ENSRNOG00000019138

Paralogs (2): CLEC3B (ENSG00000163815), CLEC3A (ENSG00000166509)

Protein

Protein identifiers

C-type lectin domain family 11 member A — Q9Y240 (reviewed: Q9Y240)

Alternative names: C-type lectin superfamily member 3, Lymphocyte secreted C-type lectin, Osteolectin, Stem cell growth factor, p47

All UniProt accessions (2): Q9Y240, M0R081

UniProt curated annotations — full annotation on UniProt →

Function. Promotes osteogenesis by stimulating the differentiation of mesenchymal progenitors into mature osteoblasts. Important for repair and maintenance of adult bone.

Subcellular location. Cytoplasm. Secreted.

Tissue specificity. Expressed in skeletal tissues including bone marrow, chondrocytes, primary ossification center-associated cells, the perichondrium and periosteum. Lower levels of expression were detected in spleen, thymus, appendix and fetal liver.

Post-translational modifications. O-glycosylated. Probably sulfated on the O-glycans.

RefSeq proteins (1): NP_002966* (*=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 (10 total): region of interest 2, disulfide bond 2, signal peptide 1, chain 1, domain 1, short sequence motif 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y240-F1	79.71	0.61

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 (2): 204–319, 296–311

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): STAEGE_EWING_FAMILY_TUMOR, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_OSSIFICATION, GFI1_01, GOMF_SIGNALING_RECEPTOR_BINDING, CUI_TCF21_TARGETS_2_UP, TGGAAA_NFAT_Q4_01, SCHUETZ_BREAST_CANCER_DUCTAL_INVASIVE_UP, MODULE_13, CASTELLANO_NRAS_TARGETS_UP, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_DN, YOSHIMURA_MAPK8_TARGETS_UP, GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_UP, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY

GO Biological Process (3): ossification (GO:0001503), positive regulation of cell population proliferation (GO:0008284), signal transduction (GO:0007165)

GO Molecular Function (3): growth factor activity (GO:0008083), carbohydrate binding (GO:0030246), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
multicellular organismal process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC11A	KIT	P10721	993
CLEC11A	KITLG	P21583	713
CLEC11A	CSF1	P09603	705
CLEC11A	CCL27	Q9Y4X3	698
CLEC11A	PDGFRA	P16234	624
CLEC11A	IL16	Q14005	597
CLEC11A	PDGFRB	P09619	592
CLEC11A	CSF1R	P07333	577
CLEC11A	CCL7	P80098	576
CLEC11A	EPHA1	P21709	548
CLEC11A	EPHA3	P29320	543
CLEC11A	LTA	P01374	542
CLEC11A	IFNA2	P01563	542
CLEC11A	ITGA11	Q9UKX5	527
CLEC11A	IL3	P08700	525

IntAct

40 interactions, top by confidence:

A	B	Type	Score
TUBA1C	TXNDC9	psi-mi:“MI:0914”(association)	0.730
UBQLN2	CLEC11A	psi-mi:“MI:0915”(physical association)	0.560
GRN	CLEC11A	psi-mi:“MI:0915”(physical association)	0.560
CLEC11A	NEFL	psi-mi:“MI:0915”(physical association)	0.560
CLEC11A	TTR	psi-mi:“MI:0915”(physical association)	0.560
CLEC11A	WFS1	psi-mi:“MI:0915”(physical association)	0.560
HTT	CLEC11A	psi-mi:“MI:0915”(physical association)	0.560
LRRC15	TCAF2	psi-mi:“MI:0914”(association)	0.560
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
CDR2	IGSF3	psi-mi:“MI:0914”(association)	0.530

BioGRID (152): PKP4 (Affinity Capture-MS), RNF13 (Affinity Capture-MS), NUP214 (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), BIRC2 (Affinity Capture-MS), NUP98 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), AMD1 (Affinity Capture-MS), ZYG11B (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), SUGP2 (Affinity Capture-MS), MYCBP2 (Affinity Capture-MS), FBXO28 (Affinity Capture-MS), VWA8 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS)

ESM2 similar proteins: D3YZZ2, O00292, O43508, O54907, O55237, O75610, O75888, P10154, P26445, P32970, P41155, P41273, P70225, Q06600, Q13477, Q14626, Q3ZDR4, Q5E9Z9, Q5RF19, Q5T7M4, Q5WR07, Q63148, Q64280, Q64385, Q6BAA4, Q6UWL6, Q6ZMM2, Q862Z7, Q86UR1, Q8BHA1, Q8N1F8, Q8NAC3, Q8NFR9, Q8R2Z0, Q99M75, Q99MF4, Q99PI8, Q9BZR6, Q9C0J1, Q9D777

Diamond homologs: O88200, O88201, P26258, Q28008, Q2KIS7, Q66KU1, Q9EPW4, Q9Y240, O75596, P05452, P10716, P12842, P20693, P23805, P35248, P43025, P49874, P50404, P55068, Q26627, Q28062, Q3SXB8, Q5U3G1, Q61361, Q61830, Q8IWL1, Q8IWL2, Q8MHZ9, Q8N1N0, Q96GW7, Q98TA4, Q9TUC5, Q9ULY5, O02659, P11226, P19999, P22897, P35246, P35247, P41317

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

508 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50723384:G:GT	donor_gain	1.0000
19:50724407:CAGT:C	acceptor_loss	1.0000
19:50724408:A:AG	acceptor_gain	1.0000
19:50724408:AGT:A	acceptor_gain	1.0000
19:50724408:AGTG:A	acceptor_gain	1.0000
19:50724409:G:GA	acceptor_gain	1.0000
19:50724409:GT:G	acceptor_gain	1.0000
19:50724409:GTG:G	acceptor_gain	1.0000
19:50724409:GTGG:G	acceptor_gain	1.0000
19:50724597:GGAGG:G	donor_gain	1.0000
19:50724598:GAGG:G	donor_gain	1.0000
19:50724598:GAGGG:G	donor_gain	1.0000
19:50724600:GG:G	donor_gain	1.0000
19:50724601:GG:G	donor_gain	1.0000
19:50724602:G:GG	donor_gain	1.0000
19:50725004:ACCC:A	acceptor_gain	1.0000
19:50725007:C:CA	acceptor_gain	1.0000
19:50723395:C:G	donor_gain	0.9900
19:50723398:G:GT	donor_gain	0.9900
19:50724092:G:GG	donor_gain	0.9900
19:50724405:C:CA	acceptor_gain	0.9900
19:50724408:AGTGG:A	acceptor_gain	0.9900
19:50724409:GTGGG:G	acceptor_gain	0.9900
19:50724559:G:GT	donor_gain	0.9900
19:50724599:AGG:A	donor_gain	0.9900
19:50724600:GGG:G	donor_gain	0.9900
19:50724602:G:GC	donor_loss	0.9900
19:50724603:TGAG:T	donor_loss	0.9900
19:50725004:ACCCG:A	acceptor_gain	0.9900
19:50725008:G:A	acceptor_gain	0.9900

AlphaMissense

2069 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50725287:G:C	W264C	0.999
19:50725287:G:T	W264C	0.999
19:50725416:G:C	W307C	0.999
19:50725416:G:T	W307C	0.999
19:50725212:G:C	W239C	0.998
19:50725212:G:T	W239C	0.998
19:50725413:G:C	W306C	0.998
19:50725413:G:T	W306C	0.998
19:50725411:T:A	W306R	0.997
19:50725411:T:C	W306R	0.997
19:50725105:T:A	C204S	0.996
19:50725106:G:C	C204S	0.996
19:50725107:C:G	C204W	0.996
19:50725203:G:C	W236C	0.996
19:50725203:G:T	W236C	0.996
19:50725210:T:A	W239R	0.996
19:50725210:T:C	W239R	0.996
19:50725285:T:A	W264R	0.996
19:50725285:T:C	W264R	0.996
19:50725381:T:A	C296S	0.996
19:50725382:G:C	C296S	0.996
19:50725418:A:C	D308A	0.996
19:50725418:A:T	D308V	0.996
19:50725451:G:A	C319Y	0.996
19:50725106:G:A	C204Y	0.995
19:50725226:A:T	D244V	0.995
19:50725054:T:A	C187S	0.994
19:50725054:T:C	C187R	0.994
19:50725055:G:C	C187S	0.994
19:50725105:T:C	C204R	0.994

dbSNP variants (sampled 300 via entrez): RS1000317965 (19:50722653 C>T), RS1000380023 (19:50722337 C>G,T), RS1001435924 (19:50722297 T>C), RS1001775312 (19:50723028 G>A,T), RS1003825496 (19:50725635 C>T), RS1003875613 (19:50724677 C>G,T), RS1004732288 (19:50724834 C>A,T), RS1005326011 (19:50726173 C>G,T), RS1005714856 (19:50721558 G>C), RS1006140546 (19:50721500 G>A), RS1007432752 (19:50723909 T>C,G), RS1007730742 (19:50724225 AG>A), RS1008090393 (19:50722292 G>A,T), RS1008851337 (19:50725041 C>G,T), RS1010226142 (19:50722322 C>A)

Disease associations

OMIM: gene MIM:604713 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004428_23	Stem cell growth factor beta levels	2.000000e-16
GCST006585_2237	Blood protein levels	4.000000e-09
GCST006585_2652	Blood protein levels	2.000000e-07
GCST010536_5	Carotid plaque maximum area	5.000000e-06
GCST010538_6	Sum of carotid plaque area	2.000000e-07
GCST010539_7	Sum of stenosis	3.000000e-06
GCST010600_8	Dietary fat liking	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006501	carotid plaque build
EFO:0010816	dietary fat liking measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	decreases methylation	1
salinomycin	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Asbestos	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	increases expression	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	affects expression	1
Fluorouracil	affects response to substance, decreases expression	1
Methapyrilene	increases methylation	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	increases expression	1

Clinical trials (associated diseases)

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