MUC20

Summary

MUC20 (mucin 20, cell surface associated, HGNC:23282) is a protein-coding gene on chromosome 3q29, encoding Mucin-20 (Q8N307). May regulate MET signaling cascade. It is a selective cancer dependency (DepMap: 16.6% of cell lines).

This gene encodes a member of the mucin protein family. Mucins are high molecular weight glycoproteins secreted by many epithelial tissues to form an insoluble mucous barrier. The C-terminus of this family member associates with the multifunctional docking site of the MET proto-oncogene and suppresses activation of some downstream MET signaling cascades. The protein features a mucin tandem repeat domain that varies between two and six copies in most individuals. Multiple variants encoding different isoforms have been found for this gene. A related pseudogene, which is also located on chromosome 3, has been identified.

Source: NCBI Gene 200958 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 26 total
• Cancer dependency (DepMap): dependent in 16.6% of screened cell lines
• MANE Select transcript: NM_001282506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23282
Approved symbol	MUC20
Name	mucin 20, cell surface associated
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14408, KIAA1359
Ensembl gene	ENSG00000176945
Ensembl biotype	protein_coding
OMIM	610360
Entrez	200958

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000423938, ENST00000436408, ENST00000445522, ENST00000447234, ENST00000480350, ENST00000485430, ENST00000498018, ENST00000867368

RefSeq mRNA: 1 — MANE Select: NM_001282506 NM_001282506

CCDS: CCDS63877

Canonical transcript exons

ENST00000447234 — 4 exons

Exon	Start	End
ENSE00001297048	195720978	195721083
ENSE00001766186	195724680	195726572
ENSE00003518158	195733150	195733551
ENSE00003617822	195729648	195729739

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 98.01.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5321 / max 46.7222, expressed in 151 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40699	0.3659	103
40698	0.1662	77

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.54	gold quality
metanephros cortex	UBERON:0010533	97.46	gold quality
lower esophagus mucosa	UBERON:0035834	96.15	gold quality
gall bladder	UBERON:0002110	94.66	gold quality
sural nerve	UBERON:0015488	94.38	gold quality
palpebral conjunctiva	UBERON:0001812	93.80	gold quality
minor salivary gland	UBERON:0001830	93.36	gold quality
rectum	UBERON:0001052	93.35	gold quality
mucosa of transverse colon	UBERON:0004991	92.43	gold quality
esophagus mucosa	UBERON:0002469	92.28	gold quality
adenohypophysis	UBERON:0002196	91.24	gold quality
transverse colon	UBERON:0001157	90.80	gold quality
mucosa of stomach	UBERON:0001199	90.76	gold quality
nasal cavity epithelium	UBERON:0005384	90.24	gold quality
right lobe of liver	UBERON:0001114	89.22	gold quality
adult mammalian kidney	UBERON:0000082	88.36	gold quality
islet of Langerhans	UBERON:0000006	88.14	gold quality
cortex of kidney	UBERON:0001225	87.79	gold quality
mouth mucosa	UBERON:0003729	87.53	gold quality
saliva-secreting gland	UBERON:0001044	87.32	gold quality
left lobe of thyroid gland	UBERON:0001120	87.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.11	gold quality
pituitary gland	UBERON:0000007	86.77	gold quality
vagina	UBERON:0000996	86.75	gold quality
body of pancreas	UBERON:0001150	86.64	gold quality
esophagus	UBERON:0001043	86.08	gold quality
right lobe of thyroid gland	UBERON:0001119	86.03	gold quality
left ovary	UBERON:0002119	85.51	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.85
E-CURD-114	yes	9.66
E-GEOD-100618	no	77.95
E-GEOD-99795	no	14.89

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• Results suggest that MUC20 is a novel regulator of the Met signaling cascade which has a role in suppression of the Grb2-Ras pathway. (PMID:15314156)
• Reflux laryngitis is associated with down-regulation of mucin gene expression. (PMID:18834073)
• MUC20 is expressed in recurrent colorectal neoplasms and may have a role in poor outcome (PMID:23787019)
• MUC20 is a novel transmembrane mucin expressed by the human corneal and conjunctival epithelia, and suggest that differential expression of MUC20 during differentiation has a role in maintaining ocular surface homeostasis. (PMID:25168902)
• A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery. (PMID:26323930)
• Results suggest that MUC20 enhances aggressive behaviors of EOC cells by activating integrin beta1 signaling and provide novel insights into the role of MUC20 in ovarian cancer metastasis. (PMID:26616226)
• High MUC20 expression is associated wit response to chemotherapy in esophageal squamous cell carcinoma. (PMID:26673820)
• increased gene expression of MUC16 and MUC20 was found in patients with remission ulcerative colitis (PMID:26770020)
• MUC20 knockdown suppresses the malignant phenotypes of PDAC cells at least partially through the inhibition of the HGF/MET pathway. (PMID:29993037)
• the combination of MUC4, MUC16 and MUC20 signature is associated with statistically significant reduced overall survival and increased hazard ratio in pancreatic, colon and stomach cancer. (PMID:30236127)
• MUC20 expression marks the receptive phase of the human endometrium. (PMID:31519421)
• Lnc-MUC20-9 binds to ROCK1 and functions as a tumor suppressor in bladder cancer. (PMID:31898364)
• Identification of oral squamous cell carcinoma markers MUC2 and SPRR1B downstream of TANGO. (PMID:33620575)
• Mucin 20 modulates proteasome capacity through c-Met signalling to increase carfilzomib sensitivity in mantle cell lymphoma. (PMID:34651428)
• A flexible summary statistics-based colocalization method with application to the mucin cystic fibrosis lung disease modifier locus. (PMID:35065708)
• Intracellular MUC20 variant 2 maintains mitochondrial calcium homeostasis and enhances drug resistance in gastric cancer. (PMID:35166958)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Muc20	ENSMUSG00000035638
rattus_norvegicus	Muc20	ENSRNOG00000001776

Protein

Protein identifiers

Mucin-20 — Q8N307 (reviewed: Q8N307)

All UniProt accessions (3): Q8N307, C9JJE7, H7C102

UniProt curated annotations — full annotation on UniProt →

Function. May regulate MET signaling cascade. Seems to decrease hepatocyte growth factor (HGF)-induced transient MAPK activation. Blocks GRB2 recruitment to MET thus suppressing the GRB2-RAS pathway. Inhibits HGF-induced proliferation of MMP1 and MMP9 expression.

Subunit / interactions. Interacts with MET; oligomerization increases affinity for MET.

Subcellular location. Secreted. Apical cell membrane. Basolateral cell membrane. Cell projection. Microvillus membrane.

Tissue specificity. Highly expressed in kidney, moderately in placenta, lung, prostate, liver, and digestive system. In the kidney, localized in the proximal tubules but not in the glomerulus or distal tubules. Detected in most of the male urogenital tract epithelia, with the exception of epididymis.

Polymorphism. The region encoding the tandem repeats is highly polymorphic. Divergence of the number of tandem repeats was seen in different cDNA libraries.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N307-1	1, hMUC20-L	yes
Q8N307-3	2, hMUC20-S

RefSeq proteins (1): NP_001269435* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR034551	MUC20	Family
IPR054051	MUC-20_rpt	Repeat

Pfam: PF21824

UniProt features (66 total): compositionally biased region 16, sequence conflict 13, repeat 12, sequence variant 12, region of interest 7, glycosylation site 3, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N307-F1	54.24	0.20

Functional residue map

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

Glycosylation sites (3): 423, 616, 622

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-5083625	Defective GALNT3 causes HFTC
R-HSA-5083632	Defective C1GALT1C1 causes TNPS
R-HSA-5083636	Defective GALNT12 causes CRCS1
R-HSA-5621480	Dectin-2 family
R-HSA-8851805	MET activates RAS signaling
R-HSA-913709	O-linked glycosylation of mucins
R-HSA-977068	Termination of O-glycan biosynthesis
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5621481	C-type lectin receptors (CLRs)
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification
R-HSA-6806834	Signaling by MET
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 91 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOZGIT_ESR1_TARGETS_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOCC_APICAL_PLASMA_MEMBRANE, OUYANG_PROSTATE_CANCER_PROGRESSION_UP, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_APICAL_PART_OF_CELL, GOCC_MICROVILLUS, GOCC_MICROVILLUS_MEMBRANE, ZHENG_BOUND_BY_FOXP3, GOCC_PLASMA_MEMBRANE_REGION, GOCC_ACTIN_BASED_CELL_PROJECTION, GOBP_CELL_SURFACE_RECEPTOR_PROTEIN_TYROSINE_KINASE_SIGNALING_PATHWAY, GOCC_GOLGI_LUMEN, GOCC_BASAL_PART_OF_CELL

GO Biological Process (1): hepatocyte growth factor receptor signaling pathway (GO:0048012)

GO Molecular Function (1): identical protein binding (GO:0042802)

GO Cellular Component (9): extracellular region (GO:0005576), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), microvillus membrane (GO:0031528), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	3
C-type lectin receptors (CLRs)	1
Signaling by MET	1
O-linked glycosylation	1
O-linked glycosylation of mucins	1
Immune System	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Innate Immune System	1
Disease	1
Metabolism of proteins	1
Signaling by Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
plasma membrane region	3
cell surface receptor protein tyrosine kinase signaling pathway	1
protein binding	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
basal part of cell	1
basal plasma membrane	1
apical part of cell	1
microvillus	1
cell projection membrane	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MUC20	MUC4	Q99102	948
MUC20	MUC13	Q9H3R2	901
MUC20	MUC1	P13931	896
MUC20	MUC12	Q9UKN1	881
MUC20	MUC17	Q685J3	865
MUC20	MUC2	Q02817	860
MUC20	MUC3A	Q02505	847
MUC20	MUC15	Q8N387	834
MUC20	MUC5B	Q9HC84	833
MUC20	MUC5AC	P98088	814
MUC20	MUC21	Q5SSG8	801
MUC20	MUC7	Q8TAX7	771
MUC20	MUC19	Q7Z5P9	761
MUC20	MUC6	Q6W4X9	730
MUC20	MUC16	Q8WXI7	719

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ALDOB	MUC20	psi-mi:“MI:0915”(physical association)	0.370
MUC20	ELOVL3	psi-mi:“MI:0915”(physical association)	0.370
MUC20	RAD51B	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): TUBB1 (Affinity Capture-MS), ARF6 (Affinity Capture-MS), TRMT44 (Affinity Capture-MS), RBM15 (Affinity Capture-MS), GTPBP2 (Affinity Capture-MS), AP3S1 (Affinity Capture-MS), FAM118B (Affinity Capture-MS), RAD51B (Affinity Capture-MS), RANGRF (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), GK (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), SLC25A14 (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), PPM1F (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YWL9, A0A0J9YY54, A0A0U1RQI7, A0A494C071, A6NNC1, A6QL64, B3KS81, D3YZV8, E2RYF7, E9Q6E9, F1LWT0, F8W0I5, O60732, P0C8Z4, P0DKJ7, P0DKJ8, P0DKL2, P0DPF3, P18751, P20930, P43537, P53353, P59797, P62521, Q01456, Q08AG5, Q12816, Q3BBV2, Q5H9R4, Q5HY64, Q5JPF3, Q6P902, Q6ZQX7, Q86T75, Q86VE3, Q86VQ3, Q8BGJ3, Q8N307, Q8N7U7, Q8N7X1

Diamond homologs: Q8BUE7, Q8N307

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

420 predictions. Top by Δscore:

Variant	Effect	Δscore
3:195729640:A:AG	acceptor_gain	1.0000
3:195729641:T:G	acceptor_gain	1.0000
3:195729642:TTGCA:T	acceptor_loss	1.0000
3:195729643:TGCAG:T	acceptor_loss	1.0000
3:195729644:GCAG:G	acceptor_loss	1.0000
3:195729645:CAGGT:C	acceptor_loss	1.0000
3:195729646:A:AG	acceptor_gain	1.0000
3:195729646:AGGT:A	acceptor_gain	1.0000
3:195729647:G:GC	acceptor_gain	1.0000
3:195729647:GGT:G	acceptor_gain	1.0000
3:195729647:GGTG:G	acceptor_gain	1.0000
3:195729647:GGTGA:G	acceptor_gain	1.0000
3:195729736:GCAG:G	donor_gain	1.0000
3:195729737:CAGG:C	donor_loss	1.0000
3:195729739:GGTG:G	donor_loss	1.0000
3:195729740:GTGA:G	donor_loss	1.0000
3:195729741:T:G	donor_loss	1.0000
3:195726570:CAGGT:C	donor_loss	0.9900
3:195726571:AGGTA:A	donor_loss	0.9900
3:195726573:GT:G	donor_loss	0.9900
3:195726574:T:G	donor_loss	0.9900
3:195729643:T:TA	acceptor_gain	0.9900
3:195729646:AG:A	acceptor_gain	0.9900
3:195729647:GG:G	acceptor_gain	0.9900
3:195729740:G:GG	donor_gain	0.9900
3:195729640:ATTT:A	acceptor_gain	0.9800
3:195726573:G:GG	donor_gain	0.9500
3:195729735:AGCAG:A	donor_gain	0.9500
3:195729736:GCAGG:G	donor_gain	0.9500
3:195720943:G:GT	donor_gain	0.9300

AlphaMissense

4506 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:195725505:T:A	I301N	0.985
3:195725505:T:G	I301S	0.985
3:195725448:T:A	I282N	0.984
3:195725448:T:G	I282S	0.984
3:195725448:T:C	I282T	0.983
3:195725505:T:C	I301T	0.983
3:195725334:T:G	I244S	0.982
3:195725391:T:G	I263S	0.982
3:195725391:T:A	I263N	0.981
3:195725391:T:C	I263T	0.981
3:195725334:T:A	I244N	0.980
3:195725334:T:C	I244T	0.980
3:195725277:T:G	I225S	0.979
3:195725277:T:C	I225T	0.977
3:195725562:T:G	I320S	0.977
3:195725277:T:A	I225N	0.976
3:195725414:A:C	S271R	0.975
3:195725416:C:A	S271R	0.975
3:195725416:C:G	S271R	0.975
3:195725471:A:C	S290R	0.975
3:195725473:C:A	S290R	0.975
3:195725473:C:G	S290R	0.975
3:195725562:T:A	I320N	0.975
3:195725562:T:C	I320T	0.975
3:195725357:A:C	S252R	0.973
3:195725359:C:A	S252R	0.973
3:195725359:C:G	S252R	0.973
3:195725474:A:C	S291R	0.972
3:195725476:C:A	S291R	0.972
3:195725476:C:G	S291R	0.972

dbSNP variants (sampled 300 via entrez): RS1000061921 (3:195733832 C>G,T), RS1000122962 (3:195731950 C>T), RS1000259119 (3:195731763 A>C), RS1000457747 (3:195730843 T>C), RS1000552837 (3:195728381 G>A), RS1001809361 (3:195728175 G>A,T), RS1001945475 (3:195727999 A>G), RS1002449683 (3:195731437 C>T), RS1002468868 (3:195729379 C>T), RS1002604629 (3:195729189 C>T), RS1002674641 (3:195733060 C>A,G,T), RS1003161657 (3:195732949 A>G), RS1003220150 (3:195732850 G>T), RS1003382590 (3:195724618 G>A,T), RS1004005375 (3:195719754 A>G)

Disease associations

OMIM: gene MIM:610360 | 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
GCST003143_18	Lung disease severity in cystic fibrosis	8.000000e-11
GCST003143_19	Lung disease severity in cystic fibrosis	3.000000e-07
GCST003143_20	Lung disease severity in cystic fibrosis	6.000000e-06
GCST003143_21	Lung disease severity in cystic fibrosis	3.000000e-11
GCST003143_22	Lung disease severity in cystic fibrosis	2.000000e-07
GCST003143_23	Lung disease severity in cystic fibrosis	7.000000e-08
GCST007876_24	Estimated glomerular filtration rate	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007744	lung disease severity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
cordycepin	increases expression	1
entinostat	decreases expression	1
licochalcone B	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Azathioprine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Nickel	decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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