EMCN

Summary

EMCN (endomucin, HGNC:16041) is a protein-coding gene on chromosome 4q24, encoding Endomucin (Q9ULC0). Endothelial sialomucin, also called endomucin or mucin-like sialoglycoprotein, which interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellular matrix.

EMCN is a mucin-like sialoglycoprotein that interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellular matrix (Kinoshita et al., 2001 [PubMed 11418125]).

Source: NCBI Gene 51705 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_016242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16041
Approved symbol	EMCN
Name	endomucin
Location	4q24
Locus type	gene with protein product
Status	Approved
Aliases	MUC14
Ensembl gene	ENSG00000164035
Ensembl biotype	protein_coding
OMIM	608350
Entrez	51705

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 28 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000296420, ENST00000305864, ENST00000502327, ENST00000502569, ENST00000502744, ENST00000506300, ENST00000506323, ENST00000510657, ENST00000511970, ENST00000512253, ENST00000897249, ENST00000897250, ENST00000897251, ENST00000897252, ENST00000897253, ENST00000897254, ENST00000897255, ENST00000897256, ENST00000897257, ENST00000897258, ENST00000897259, ENST00000897260, ENST00000897261, ENST00000897262, ENST00000956441, ENST00000956442, ENST00000956443, ENST00000956444, ENST00000956445, ENST00000956446, ENST00000956447, ENST00000956448, ENST00000956449

RefSeq mRNA: 2 — MANE Select: NM_016242 NM_001159694, NM_016242

CCDS: CCDS3655, CCDS54782

Canonical transcript exons

ENST00000296420 — 12 exons

Exon	Start	End
ENSE00001080682	100421282	100421377
ENSE00001080684	100423312	100423404
ENSE00001080686	100423021	100423080
ENSE00001080690	100417117	100417141
ENSE00001080691	100415898	100415959
ENSE00001338708	100410282	100410355
ENSE00001847531	100395341	100398373
ENSE00001899740	100517851	100518022
ENSE00003491386	100479917	100480039
ENSE00003506996	100475038	100475109
ENSE00003564147	100465423	100465539
ENSE00003690507	100447533	100447571

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 97.64.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9220 / max 649.0163, expressed in 447 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53318	5.1361	389
53321	0.6991	195
53315	0.6640	218
53317	0.6469	232
53320	0.2938	120
53319	0.2353	121
53316	0.1392	83
53323	0.0899	12
53322	0.0178	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.64	gold quality
lower lobe of lung	UBERON:0008949	95.39	gold quality
metanephros cortex	UBERON:0010533	95.10	gold quality
parietal pleura	UBERON:0002400	94.14	gold quality
skin of hip	UBERON:0001554	94.10	gold quality
renal medulla	UBERON:0000362	93.55	gold quality
omental fat pad	UBERON:0010414	93.52	gold quality
peritoneum	UBERON:0002358	93.49	gold quality
right lobe of thyroid gland	UBERON:0001119	93.34	gold quality
visceral pleura	UBERON:0002401	93.34	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.32	gold quality
adult mammalian kidney	UBERON:0000082	93.14	gold quality
pleura	UBERON:0000977	93.14	gold quality
right lung	UBERON:0002167	93.02	gold quality
gall bladder	UBERON:0002110	92.49	gold quality
tendon	UBERON:0000043	92.21	gold quality
thyroid gland	UBERON:0002046	92.13	gold quality
left lobe of thyroid gland	UBERON:0001120	91.97	gold quality
vena cava	UBERON:0004087	91.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.89	gold quality
adrenal tissue	UBERON:0018303	91.89	gold quality
urethra	UBERON:0000057	91.83	gold quality
adipose tissue	UBERON:0001013	91.69	gold quality
heart right ventricle	UBERON:0002080	91.02	gold quality
connective tissue	UBERON:0002384	91.00	gold quality
myocardium	UBERON:0002349	90.75	gold quality
pericardium	UBERON:0002407	90.62	gold quality
seminal vesicle	UBERON:0000998	90.47	gold quality
upper lobe of lung	UBERON:0008948	90.31	gold quality
left ventricle myocardium	UBERON:0006566	90.30	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	6810.89
E-CURD-119	yes	5765.64
E-MTAB-11268	yes	2965.10
E-GEOD-124472	yes	2723.94
E-ANND-2	yes	2681.94
E-HCAD-15	yes	2048.56
E-MTAB-8142	yes	1137.90
E-GEOD-135922	yes	555.32
E-MTAB-10287	yes	84.85
E-HCAD-10	yes	63.70
E-GEOD-134144	yes	47.25
E-HCAD-1	yes	45.02
E-HCAD-11	yes	41.02
E-MTAB-6701	yes	33.84
E-MTAB-8410	yes	32.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, GATA2

miRNA regulators (miRDB)

109 targeting EMCN, 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-3134	100.00	66.43	777
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524

Literature-anchored findings (GeneRIF, showing 10)

• A significant association between EMCN and rheumatoid arthritis susceptibility was detected in our Japanese study population. The EMCN allele conferring rheumatoid arthritis susceptibility may also contribute to the pathogenesis of rheumatoid arthritis. (PMID:21159824)
• Knockdown of endomucin markedly attenuated endothelial cell growth, migration and tube formation. (PMID:21666600)
• These results indicate that endomucin prevents leukocyte contact with adhesion molecules in non-inflamed tissues and that downregulation of endomucin is critical to facilitate adhesion of leukocytes into inflamed tissues. (PMID:26831939)
• In contrast, endomucin (EMCN) is present on the lymphatic sinus endothelium and not on lymphatic endothelium of the subcapsular sinus. Moreover, both murine and human MSR1 on lymphatic endothelium of the SS bind lymphocytes and in in vivo studies MSR1 regulates entrance of lymphocytes from the SS to the lymph node parenchyma (PMID:27601677)
• Human adult HSCs can be discriminated from lineage-committed HPCs by the expression of endomucin. (PMID:29986855)
• ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface. (PMID:32193206)
• Elements of the Endomucin Extracellular Domain Essential for VEGF-Induced VEGFR2 Activity. (PMID:32517158)
• MUC14-Related ncRNA-mRNA Network in Breast Cancer. (PMID:34828282)
• Endomucin selectively regulates vascular endothelial growth factor receptor-2 endocytosis through its interaction with AP2. (PMID:38605348)
• Non-endothelial expression of endomucin in the mouse and human choroid. (PMID:39153592)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Emcn	ENSMUSG00000054690
rattus_norvegicus	Emcn	ENSRNOG00000022910

Protein

Protein identifiers

Endomucin — Q9ULC0 (reviewed: Q9ULC0)

Alternative names: Endomucin-2, Gastric cancer antigen Ga34, Mucin-14

All UniProt accessions (4): D6RHW5, H0YAA7, Q4W5J1, Q9ULC0

UniProt curated annotations — full annotation on UniProt →

Function. Endothelial sialomucin, also called endomucin or mucin-like sialoglycoprotein, which interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellular matrix.

Subcellular location. Cell membrane. Membrane Secreted.

Tissue specificity. Expressed in heart, kidney and lung.

Post-translational modifications. Highly O-glycosylated. Sialic acid-rich glycoprotein.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9ULC0-1	1	yes
Q9ULC0-2	2
Q9ULC0-3	3

RefSeq proteins (2): NP_001153166, NP_057326* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010740	Endomucin	Family

Pfam: PF07010

UniProt features (18 total): glycosylation site 6, splice variant 2, topological domain 2, compositionally biased region 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULC0-F1	52.13	0.06

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 237

Glycosylation sites (6): 28, 98, 104, 164, 178, 19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 146 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, chr4q24, CAIRO_HEPATOBLASTOMA_CLASSES_DN, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, DELYS_THYROID_CANCER_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX5_UP, BERTUCCI_INVASIVE_CARCINOMA_DUCTAL_VS_LOBULAR_DN, BROWN_MYELOID_CELL_DEVELOPMENT_UP, AACTTT_UNKNOWN, CAIRO_HEPATOBLASTOMA_UP, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, P300_01, CUI_TCF21_TARGETS_2_DN, RGAGGAARY_PU1_Q6

GO Biological Process (4): hematopoietic stem cell homeostasis (GO:0061484), angiogenesis (GO:0001525), regulation of cell adhesion (GO:0030155), cell-cell adhesion (GO:0098609)

GO Molecular Function (2): protein binding (GO:0005515), carbohydrate binding (GO:0030246)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell adhesion	2
binding	2
cellular anatomical structure	2
homeostasis of number of cells	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of cellular process	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

1422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMCN	OSGEP	Q9NPF4	901
EMCN	MUC1	P13931	790
EMCN	PECAM1	P16284	721
EMCN	CD300LG	Q6UXG3	689
EMCN	PODXL	O00592	684
EMCN	LYVE1	Q9Y5Y7	677
EMCN	SELL	P14151	675
EMCN	MUC12	Q9UKN1	647
EMCN	CD34	P28906	639
EMCN	CDH5	P33151	605
EMCN	SCGB1A1	P11684	582
EMCN	DLL4	Q9NR61	577
EMCN	MUC3A	Q02505	575
EMCN	OVGP1	Q12889	550
EMCN	FGF2	P09038	547

IntAct

2 interactions, top by confidence:

A	B	Type	Score
EMCN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): EMCN (Affinity Capture-Western), SGTB (Two-hybrid), PPP1R9A (Affinity Capture-MS), EMCN (Biochemical Activity), MPRIP (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), PLEKHG3 (Affinity Capture-MS), CRYGD (Affinity Capture-MS), NEXN (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y7Y5, O00592, O55145, O57604, P03224, P13838, P14220, P15702, P16150, P20934, P28906, P34910, P59647, P70628, P97525, P97808, Q01036, Q1ECS6, Q28270, Q28645, Q3MIW9, Q3TNW5, Q52S86, Q5HZB0, Q5RFI9, Q5XI99, Q62011, Q64314, Q66676, Q6MG22, Q6R8J2, Q6UXF1, Q7TST5, Q80XH2, Q8BHE4, Q8JZQ0, Q8MJJ2, Q8N131, Q8VD58, Q91Z22

Diamond homologs: Q5RFI9, Q6AY82, Q9R0H2, Q9ULC0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1832 predictions. Top by Δscore:

Variant	Effect	Δscore
4:100415897:CCAGA:C	donor_gain	1.0000
4:100415958:GTCTA:G	acceptor_loss	1.0000
4:100415960:C:CC	acceptor_gain	1.0000
4:100415960:C:CG	acceptor_loss	1.0000
4:100415964:T:C	acceptor_gain	1.0000
4:100415964:T:TC	acceptor_gain	1.0000
4:100423401:CTAC:C	acceptor_gain	1.0000
4:100446064:T:TA	donor_gain	1.0000
4:100446095:C:A	donor_gain	1.0000
4:100447574:T:C	acceptor_gain	1.0000
4:100447574:T:TC	acceptor_gain	1.0000
4:100465417:AC:A	donor_loss	1.0000
4:100465418:CT:C	donor_loss	1.0000
4:100465419:TTA:T	donor_loss	1.0000
4:100465420:TACT:T	donor_loss	1.0000
4:100465421:A:AC	donor_gain	1.0000
4:100465421:A:C	donor_loss	1.0000
4:100465421:ACT:A	donor_gain	1.0000
4:100465422:C:CA	donor_gain	1.0000
4:100465422:CT:C	donor_gain	1.0000
4:100465422:CTC:C	donor_gain	1.0000
4:100465422:CTCT:C	donor_gain	1.0000
4:100465422:CTCTT:C	donor_gain	1.0000
4:100465535:CAATC:C	acceptor_gain	1.0000
4:100465537:ATC:A	acceptor_gain	1.0000
4:100465538:TC:T	acceptor_gain	1.0000
4:100465539:CC:C	acceptor_gain	1.0000
4:100465540:C:A	acceptor_loss	1.0000
4:100465540:C:CC	acceptor_gain	1.0000
4:100465541:T:C	acceptor_loss	1.0000

AlphaMissense

1667 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:100415930:A:G	L240P	0.994
4:100421338:G:T	T203K	0.993
4:100421338:G:C	T203R	0.990
4:100415921:A:T	V243D	0.989
4:100415927:A:G	L241P	0.989
4:100415930:A:T	L240H	0.986
4:100415917:C:A	K244N	0.985
4:100415917:C:G	K244N	0.985
4:100415927:A:T	L241H	0.983
4:100415932:C:A	K239N	0.983
4:100415932:C:G	K239N	0.983
4:100415934:T:C	K239E	0.982
4:100415930:A:C	L240R	0.980
4:100415918:T:A	K244M	0.977
4:100415924:G:A	T242I	0.977
4:100421359:A:T	V196D	0.974
4:100415927:A:C	L241R	0.973
4:100421365:G:C	P194R	0.973
4:100415919:T:C	K244E	0.972
4:100415945:T:A	K235I	0.970
4:100421325:A:C	F207L	0.970
4:100421325:A:T	F207L	0.970
4:100421327:A:G	F207L	0.970
4:100421335:A:C	L204R	0.968
4:100421315:C:G	G211R	0.967
4:100415918:T:G	K244T	0.966
4:100421341:A:T	I202K	0.966
4:100421335:A:G	L204P	0.963
4:100415933:T:A	K239M	0.961
4:100415938:G:C	S237R	0.961

dbSNP variants (sampled 300 via entrez): RS1000003635 (4:100456596 T>A,C), RS1000017266 (4:100494247 G>A,C), RS1000052444 (4:100413140 A>C,G), RS1000101714 (4:100510050 G>T), RS1000102073 (4:100418982 G>A), RS1000120713 (4:100451918 T>C), RS1000121858 (4:100463848 G>A), RS1000129397 (4:100482396 A>C,G), RS1000147857 (4:100443431 T>A,C), RS1000154506 (4:100419124 G>T), RS1000162248 (4:100482678 G>A,T), RS1000178807 (4:100456118 C>T), RS1000191205 (4:100462192 C>A,G), RS1000213757 (4:100412696 AT>A,ATT), RS1000268908 (4:100406190 T>C)

Disease associations

OMIM: gene MIM:608350 | 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
GCST001520_3	Response to angiotensin II receptor blocker therapy	5.000000e-06
GCST002790_2	Food allergy	3.000000e-06
GCST003999_23	Nose size	3.000000e-07
GCST006394_67	Intraocular pressure	2.000000e-10
GCST006412_42	Intraocular pressure	5.000000e-09
GCST006606_10	Response to TNF inhibitor in rheumatoid arthritis (change in swollen 28-joint count)	8.000000e-08
GCST008161_122	Waist circumference adjusted for body mass index	9.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007016	food allergy measurement
EFO:0004695	intraocular pressure measurement
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
FR900359	decreases phosphorylation	1
bisphenol A	affects cotreatment, decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
trichostatin A	decreases expression	1
cobaltous chloride	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Polychlorinated Biphenyls	affects expression	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
Warfarin	decreases expression	1
Cadmium Chloride	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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