MUC2

Summary

MUC2 (mucin 2, oligomeric mucus/gel-forming, HGNC:7512) is a protein-coding gene on chromosome 11p15.5, encoding Mucin-2 (Q02817). Coats the epithelia of the intestines and other mucus membrane-containing organs to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces.

This gene encodes a member of the mucin protein family. Mucins are high molecular weight glycoproteins produced by many epithelial tissues. The protein encoded by this gene is secreted and forms an insoluble mucous barrier that protects the gut lumen. The protein polymerizes into a gel of which 80% is composed of oligosaccharide side chains by weight. The protein features a central domain containing tandem repeats rich in threonine and proline that varies between 50 and 115 copies in different individuals. Downregulation of this gene has been observed in patients with Crohn disease and ulcerative colitis.

Source: NCBI Gene 4583 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_002457

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7512
Approved symbol	MUC2
Name	mucin 2, oligomeric mucus/gel-forming
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	MLP, MUC-2
Ensembl gene	ENSG00000198788
Ensembl biotype	protein_coding
OMIM	158370
Entrez	4583

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000361558, ENST00000674892, ENST00000675028

RefSeq mRNA: 1 — MANE Select: NM_002457 NM_002457

Canonical transcript exons

ENST00000361558 — 49 exons

Exon	Start	End
ENSE00001297768	1100757	1100954
ENSE00001310401	1102417	1102664
ENSE00001315516	1094142	1100025
ENSE00001321690	1103274	1103457
ENSE00001415295	1075651	1075921
ENSE00002312917	1104733	1104911
ENSE00003628285	1101756	1101930
ENSE00003659106	1103781	1104009
ENSE00003672538	1101223	1101446
ENSE00003712504	1090764	1090911
ENSE00003712878	1110136	1110511
ENSE00003719910	1108173	1108295
ENSE00003720560	1082285	1082402
ENSE00003720733	1082878	1082988
ENSE00003721178	1077454	1077568
ENSE00003722516	1077952	1078042
ENSE00003722542	1085554	1085606
ENSE00003723426	1084592	1084718
ENSE00003725210	1086246	1086397
ENSE00003726723	1082481	1082619
ENSE00003726887	1093534	1093551
ENSE00003727241	1074875	1074977
ENSE00003728323	1078123	1078232
ENSE00003728969	1105511	1105611
ENSE00003729034	1083425	1083562
ENSE00003730516	1108548	1108646
ENSE00003731939	1083077	1083146
ENSE00003732508	1085068	1085323
ENSE00003733783	1086735	1086873
ENSE00003736745	1092399	1092442
ENSE00003738192	1105856	1105887
ENSE00003741054	1092844	1093047
ENSE00003742384	1107650	1107754
ENSE00003743832	1109901	1110027
ENSE00003744586	1088258	1088497
ENSE00003744843	1107086	1107263
ENSE00003744886	1081662	1081787
ENSE00003745523	1109647	1109686
ENSE00003746993	1084291	1084385
ENSE00003748903	1087755	1087865
ENSE00003748974	1089942	1090073
ENSE00003749019	1083653	1083817
ENSE00003749617	1085745	1085845
ENSE00003750028	1089509	1089665
ENSE00003750349	1078312	1078522
ENSE00003752750	1108004	1108044
ENSE00003753976	1109281	1109409
ENSE00003754413	1105303	1105372
ENSE00003754425	1087947	1088126

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 99.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.5582 / max 2926.2872, expressed in 104 samples.

FANTOM5 promoters (35 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112354	3.6416	43
206091	0.2725	21
112366	0.2237	19
206113	0.1831	22
206096	0.1496	15
112371	0.1221	22
206099	0.0978	11
206110	0.0896	11
112370	0.0798	11
112372	0.0683	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.38	gold quality
rectum	UBERON:0001052	96.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.54	gold quality
duodenum	UBERON:0002114	95.08	gold quality
small intestine	UBERON:0002108	93.91	gold quality
transverse colon	UBERON:0001157	92.29	gold quality
vermiform appendix	UBERON:0001154	84.86	gold quality
intestine	UBERON:0000160	83.67	gold quality
colonic epithelium	UBERON:0000397	81.17	gold quality
colon	UBERON:0001155	80.25	gold quality
smooth muscle tissue	UBERON:0001135	69.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	63.13	gold quality
right coronary artery	UBERON:0001625	51.13	gold quality
urinary bladder	UBERON:0001255	50.29	gold quality
lower esophagus mucosa	UBERON:0035834	49.09	gold quality
muscle tissue	UBERON:0002385	46.55	gold quality
endocervix	UBERON:0000458	46.08	gold quality
bone marrow cell	CL:0002092	45.37	gold quality
sural nerve	UBERON:0015488	45.10	gold quality
prostate gland	UBERON:0002367	45.02	gold quality
body of stomach	UBERON:0001161	44.70	gold quality
uterine cervix	UBERON:0000002	44.44	gold quality
stomach	UBERON:0000945	44.08	gold quality
liver	UBERON:0002107	43.76	gold quality
right lobe of liver	UBERON:0001114	43.61	gold quality
apex of heart	UBERON:0002098	43.14	silver quality
islet of Langerhans	UBERON:0000006	42.58	silver quality
pancreas	UBERON:0001264	42.52	silver quality
right lung	UBERON:0002167	42.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	20061.96
E-MTAB-8410	yes	11266.26
E-GEOD-125970	yes	6611.52
E-ANND-3	yes	4.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF1, ATOH1, CDX1, CDX2, CREB1, CTCF, FOXA1, FOXA2, GATA4, GATA5, JUN, NFATC3, NFKB1, NFKB, NR1H4, RELA, SMAD4, SOX9, SP1, SP3, SPDEF, TBP, TP53, ZHX2

miRNA regulators (miRDB)

8 targeting MUC2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-4740-5P	96.25	67.96	726

Literature-anchored findings (GeneRIF, showing 40)

• MUC2 represents a marker for low-grade dysplasia and the subtype of mucinous carcinomas (PMID:11813869)
• De novo expression of the Muc2 gene in pancreas carcinoma cells is triggered by promoter demethylation (PMID:11893907)
• MUC2 upregulated by Phorbol 12-myristate 13-acetate via Ras, ERK, NF-kB (PMID:12077118)
• MUC2 is a reliable molecular marker for pseudomyxoma peritonei. (PMID:12218214)
• Data show that nontypeable Haemophilus influenzae utilizes the TGF-beta-Smad signaling pathway together with the TLR2-MyD88-TAK1-NIK-IKKbeta/gamma-IkappaBalpha pathway to mediate NF-kappaB-dependent MUC2 mucin transcription. (PMID:12237307)
• increase in expression more signficantly in response to p53 than to p21 (PMID:12374798)
• in human pulmonary epithelial cells, IL-1beta activates ERK or p38 to induce COX-2 production, which in turn induces MUC2 and MUC5AC production. (PMID:12391274)
• MUC2 gene expression and mucin secretion are regulated by IL1beta (PMID:12482999)
• MUC2 expression in gastric cells is regulated by promoter methylation and further indicate that two specific cytosine guaine dinucleotide (CpG) sites may play a particularly important regulatory role. (PMID:12490305)
• The expression of MUC2 gene products in pancreatic cancer cells correlated well with methylation of the proximal region of the promoter (PMID:12527922)
• These results suggest that CDX2, but not CDX1, interacts with the MUC2 promoter and activates MUC2 transcription, and plays an important role in the differentiation of goblet cells. (PMID:12559945)
• MUC2 mucin has an autocatalytic cleavage in the C terminus at the low pH of the late secretory pathway (PMID:12582180)
• The anti-MUC2 non-VNTR antibody in the goblet cells of adenomas revealed a staining pattern of increased cytoplasmic, Golgi and membrane staining with no change in goblet vesicle reactivity compared with normal controls (PMID:12820724)
• findings show that MUC2 mRNA expression is differently controlled by IL-4, IL-13, or TNF-alpha in LS174T and HT29 cells; the mitogen-activated protein kinase pathway plays a role in the MUC2 mRNA expression induced by those cytokines in both cell lines (PMID:12848848)
• Cdx-2 activates the expression of MUC2 mucin gene in gastric cells, inducing an intestinal transdifferentiation phenotype that parallels what is observed both in intestinal metaplasia and some gastric carci (PMID:14525978)
• mucin is transcriptionally upregulated in an NF-kappaB- and p38-dependent manner when homogeneous cultures of epithelial cells are exposed to dsRNA (PMID:14550542)
• expression pattern of MUC2 in salivary gland neoplasia may be of value for the classification of salivary gland tumors (PMID:14616551)
• Aberrant expression of CDX2 is closely related to the overexpression of MUC2 in mucinous intrahepatic cholangiocarcinoma and intraductal papillary neoplasia of the liver associated with hepatolithiasis. (PMID:15048136)
• complete genomic (exon/intron) organization (PMID:15081123)
• CDX2 and MUC2 genes are repressed by SOX9 in intestinal epithelium (PMID:15240568)
• MUC2 mucin expression is increased in response to adenosine in airway epithelial cells. (PMID:15345696)
• TNF-alpha causes a net up-regulation of MUC2 gene expression in cultured colon cancer cells because NF-kappaB transcriptional activation of this gene is able to counter-balance the suppressive effects of the JNK pathway (PMID:15665513)
• PI3-K promotes the expression of TFF3 and MUC2 and that the PI3-K pathway may play a pivotal role in intestinal goblet cell differentiation. (PMID:15733066)
• MUC5AC and MUC2, TFF1 and TFF3, APC and p21 in subsets of colorectal polyps and cancers suggests a distinct pathway of pathogenesis of mucinous carcinoma of the colorectum (PMID:16142311)
• MUC1, MUC5B and MUC8, but not MUC2 or MUC5AC, are up-regulated in endometrial adenocarcinomas (PMID:16188033)
• CREB/ATF1 and c-Jun were shown to bind to an oligonucleotide encompassing a distal, conserved CREB/AP1 site in the 5’-flanking region of the MUC2 gene, and this cis element was shown to mediate promoter reporter activation by VIP (PMID:16227528)
• Galectin-3 up-regulation of MUC2 transcription occurs at the level of transcription through AP-1 activation in colon cancer cells (PMID:16285957)
• MUC2-positive tumours were significantly associated with the gain of 19p13.3, compared with MUC2-negative tumours (41.2 vs 5.9%, P=0.0391). (PMID:16447040)
• Overexpresssed in the progression and lymphatic metastasis of prostate cancer. (PMID:16475027)
• careful systemic surveillance is needed to detect coexisting gastrointestinal cancer for subtypes of intraductal papillary mucinous neoplasms with MUC2 expression. (PMID:16552339)
• histone H3 modification in the 5’ flanking region play an important role in MUC2 gene expression, possibly affecting DNA methylation (PMID:16721789)
• High expression of MUC2 was associated with mucinous subtype of the WHO classification and with group II of Goseki’s classification identified by the major component of a particular tumor. (PMID:16733847)
• Data show that the C-terminal domain of Muc2 is specifically targeted by Entamoeba histolytica cysteine proteases, while the N-terminal domain is resistant to proteolysis. (PMID:16754877)
• Aberrant intestinal expression and allelic variant MUC2 is associated with inflammatory bowel disease. (PMID:17058067)
• a decrease in MUC2 expression and staining of MUC5AC in non-goblet-like cells are observed in progression of preneoplastic lesions (PMID:17203232)
• MUC2 was isolated from an adenomatous colorectal neoplasm tumor line and the effect of chitinase on it was studied. (PMID:17321686)
• Histiocytoid features of invasive lobular carcinoma is immunopositive for MUC2. (PMID:17333267)
• Upregulation of MUC2 reflects intestinal metaplasia in Barrett’s esophagus (PMID:17401217)
• In conclusion, this study demonstrates the important role for methylation and/or histone modifications in regulating the 11p15 mucin genes in epithelial cancer cells. (PMID:17471237)
• structural analysis of L- and D-amino acid-substituted mucin 2 epitope peptides (PMID:17509526)

Cross-species orthologs

0 orthologs

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), CHRDL1 (ENSG00000101938), TECTA (ENSG00000109927), VWF (ENSG00000110799), MUC5B (ENSG00000117983), KCP (ENSG00000135253), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), OTOGL (ENSG00000165899), VWCE (ENSG00000167992), VWC2L (ENSG00000174453), MUC6 (ENSG00000184956), OTOG (ENSG00000188162), VWC2 (ENSG00000188730), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

Mucin-2 — Q02817 (reviewed: Q02817)

Alternative names: Intestinal mucin-2

All UniProt accessions (2): A0A6Q8PFN2, A0A6Q8PGX3

UniProt curated annotations — full annotation on UniProt →

Function. Coats the epithelia of the intestines and other mucus membrane-containing organs to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. Major constituent of the colon mucus, which is mainly formed by large polymeric networks of MUC2 secreted by goblet cells that cover the exposed surfaces of intestine. MUC2 networks form hydrogels that guard the underlying epithelium from pathogens and other hazardous matter entering from the outside world, while permitting nutrient absorption and gas exchange. Acts as a divalent copper chaperone that protects intestinal cells from copper toxicity and facilitates nutritional copper unptake into cells. Binds both Cu(2+) and its reduced form, Cu(1+), at two juxtaposed binding sites: Cu(2+), once reduced to Cu(1+) by vitamin C (ascorbate) or other dietary antioxidants, transits to the other binding site. MUC2-bound Cu(1+) is protected from oxidation in aerobic environments, and can be released for nutritional delivery to cells. Mucin gels store antimicrobial molecules that participate in innate immunity. Mucin glycoproteins also house and feed the microbiome, lubricate tissue surfaces, and may facilitate the removal of contaminants and waste products from the body. Goblet cells synthesize two forms of MUC2 mucin that differ in branched chain O-glycosylation and the site of production in the colon: a (1) ’thick’ mucus that wraps the microbiota to form fecal pellets is produced in the proximal, ascending colon. ‘Thick’ mucus transits along the descending colon and is lubricated by a (2) ’thin’ MUC2 mucus produced in the distal colon which adheres to the ’thick’ mucus.

Subunit / interactions. Homomultimer; disulfide-linked. The N- and C-terminus mediate their assembly into higher order structures to form filaments. The CTCK domains of two polypeptides associate in the endoplasmic reticulum to generate intermolecularly disulfide-bonded dimers. These dimers progress to the Golgi apparatus, which is a more acidic environment than the endoplasmic reticulum. Under acidic conditions, the N-termini form non-covalent intermolecular interactions that juxtapose assemblies of the third VWD domain (VWD3) from different CTCK-linked dimers. The VWD3 assemblies then become disulfide bonded to one another to produce long, disulfide-linked polymers that remain highly compact until secretion. Interacts with FCGBP. Interacts with AGR2; disulfide-linked. (Microbial infection) Interacts in vitro with L.monocytogenes internalin proteins InlB, InlC and InlJ; for InlC binding is slightly better at pH 5.5, (the pH of the intestine) than at pH 7.4.

Subcellular location. Secreted.

Tissue specificity. Colon, small intestine, colonic tumors, bronchus, cervix and gall bladder.

Post-translational modifications. O-glycosylated. O-glycosylation is required for mucin assembly. Goblet cells synthesize two forms of mucin that differ in branched chain O-glycosylation and the site of production in the colon. May undergo proteolytic cleavage in the outer mucus layer of the colon, contributing to the expanded volume and loose nature of this layer which allows for bacterial colonization in contrast to the inner mucus layer which is dense and devoid of bacteria. At low pH of 6 and under, undergoes autocatalytic cleavage in vitro in the N-terminal region of the fourth VWD domain. It is likely that this also occurs in vivo and is triggered by the low pH of the late secretory pathway.

Domain organisation. The CTCK domain mediates interchain disulfide bonds with another molecule of MUC2.

Polymorphism. The number of repeats is highly polymorphic and varies among different alleles.

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001007	VWF_dom	Domain
IPR001846	VWF_type-D	Domain
IPR002919	TIL_dom	Domain
IPR006207	Cys_knot_C	Domain
IPR014853	VWF/SSPO/ZAN-like_Cys-rich_dom	Domain
IPR025155	WxxW_domain	Domain
IPR036084	Ser_inhib-like_sf	Homologous_superfamily
IPR050780	Mucin_vWF_Thrombospondin_sf	Family
IPR058753	TIL_OTOGL_Mucin	Domain

Pfam: PF00094, PF01826, PF08742, PF13330, PF23244, PF25962

UniProt features (536 total): strand 137, sequence conflict 111, disulfide bond 59, helix 50, glycosylation site 45, binding site 35, turn 26, repeat 21, compositionally biased region 14, sequence variant 11, mutagenesis site 9, domain 8, region of interest 6, signal peptide 1, chain 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
8CK2	X-RAY DIFFRACTION	1.5
6TM6	X-RAY DIFFRACTION	1.63
7PRL	X-RAY DIFFRACTION	2.48
6RBF	X-RAY DIFFRACTION	2.7
6TM2	ELECTRON MICROSCOPY	2.95
7A5O	ELECTRON MICROSCOPY	2.95
7QCU	ELECTRON MICROSCOPY	3.25
7QCL	ELECTRON MICROSCOPY	3.36
7PP6	ELECTRON MICROSCOPY	3.4
7QCN	ELECTRON MICROSCOPY	3.4
7POV	ELECTRON MICROSCOPY	3.8
8S03	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q02817 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Catalytic / active sites (1): 4596–4597 (cleavage; by autolysis; in vitro)

Ligand- & substrate-binding residues (35): 34; 49; 146; 154; 156; 171; 173; 175; 180; 277; 324; 326 …

Post-translational modifications (1): 21

Disulfide bonds (59): 37–169, 59–206, 67–166, 218–255, 225–250, 237–275, 257–263, 265–291, 295–329, 308–321, 312–351, 331–345, 353–375, 370–387, 373–382, 391–528, 413–563, 435–443, 574–619, 588–614 …

Glycosylation sites (45): 1269, 1270, 1272, 1275, 1276, 1281, 1282, 1287, 1291, 1292, 1293, 1296, 1297, 1787, 1820, 4449, 4461, 4472, 4483, 4532 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
32	decreased binding to cu(2+).
34	slightly decreased binding to cu(2+).
146	decreased binding to cu(1+) without affecting binding to cu(2+). abolished binding to cu(1+); when associated with l-154
154	decreased binding to cu(1+) without affecting binding to cu(2+). abolished binding to cu(1+); when associated with l-146
277	decreased binding to cu(2+).
322	decreased binding to cu(2+).
326	decreased binding to cu(1+) without affecting binding to cu(2+). abolished binding to cu(1+); when associated with l-146
1088	does not abolish homodimerization. does not abolish ability to form filaments; when associated with a-1130.
1130	impaired formation of intermolecular disulfide bonds; inducing a mixture of monomers and homodimers. does not abolish ab

Function

Pathways and Gene Ontology

Reactome pathways

6 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-913709	O-linked glycosylation of mucins
R-HSA-977068	Termination of O-glycan biosynthesis

MSigDB gene sets: 81 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_DIGESTION, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_RESPONSE_TO_COPPER_ION, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_RESPONSE_TO_METAL_ION, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_MAINTENANCE_OF_GASTROINTESTINAL_EPITHELIUM, GOBP_DETOXIFICATION, GOBP_SECRETION, GOBP_DIGESTIVE_SYSTEM_PROCESS, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_BODY_FLUID_SECRETION, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_EPITHELIAL_STRUCTURE_MAINTENANCE

GO Biological Process (4): detoxification of copper ion (GO:0010273), maintenance of gastrointestinal epithelium (GO:0030277), host-mediated modulation of intestinal microbiota composition (GO:0048874), mucus secretion (GO:0070254)

GO Molecular Function (4): cupric ion binding (GO:1903135), cuprous ion binding (GO:1903136), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (6): Golgi lumen (GO:0005796), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), inner mucus layer (GO:0070702), outer mucus layer (GO:0070703), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	3
C-type lectin receptors (CLRs)	1
O-linked glycosylation	1
O-linked glycosylation of mucins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
copper ion binding	2
mucus layer	2
detoxification of inorganic compound	1
stress response to copper ion	1
epithelial structure maintenance	1
digestive system process	1
homeostasis of number of cells	1
host-mediated perturbation of symbiont process	1
body fluid secretion	1
secretion by tissue	1
protein binding	1
binding	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2057 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MUC2	MUC6	Q6W4X9	983
MUC2	MUC1	P13931	944
MUC2	MUC4	Q99102	938
MUC2	MUC7	Q8TAX7	933
MUC2	MUC13	Q9H3R2	915
MUC2	TFF3	Q07654	894
MUC2	MUC12	Q9UKN1	885
MUC2	MUC17	Q685J3	884
MUC2	FCGBP	Q9Y6R7	866
MUC2	CDX2	Q99626	863
MUC2	MUC20	Q8N307	860
MUC2	MUC3A	Q02505	803
MUC2	KRT20	P35900	793
MUC2	MUC5AC	P98088	785
MUC2	MUC16	Q8WXI7	781
MUC2	MUC15	Q8N387	781

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MUC2	AGR2	psi-mi:“MI:0915”(physical association)	0.660
AGR2	MUC2	psi-mi:“MI:0915”(physical association)	0.660
A2M	MUC2	psi-mi:“MI:0915”(physical association)	0.400
MUC2	MLH1	psi-mi:“MI:0915”(physical association)	0.370
CFTR		psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): MUC2 (Affinity Capture-MS), MUC2 (Biochemical Activity), MUC2 (Affinity Capture-MS), MUC2 (Two-hybrid)

ESM2 similar proteins: A1A5Y0, A2ASQ1, A2VEC9, D3ZTE0, F7A4A7, O08523, O08644, O15197, O55225, P00748, P0C0K6, P0C0K7, P15306, P25304, P57999, P58459, P70505, P80012, P98167, Q00657, Q02817, Q04962, Q2PC93, Q3U492, Q53RD9, Q62635, Q6UVK1, Q6ZRI0, Q700K0, Q769J6, Q76LX8, Q80YA8, Q80YC5, Q80Z19, Q8CG65, Q8CJ69, Q8IU80, Q8K480, Q8N8U9, Q8R4Y4

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATOH1	“up-regulates quantity by expression”	MUC2	“transcriptional regulation”
CDX2	“up-regulates quantity by expression”	MUC2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	66
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

6313 predictions. Top by Δscore:

Variant	Effect	Δscore
11:1075646:CTCAG:C	acceptor_gain	1.0000
11:1075647:TCAG:T	acceptor_gain	1.0000
11:1075648:CA:C	acceptor_loss	1.0000
11:1075648:CAG:C	acceptor_gain	1.0000
11:1075649:A:AG	acceptor_gain	1.0000
11:1075649:AGA:A	acceptor_gain	1.0000
11:1075649:AGAG:A	acceptor_gain	1.0000
11:1075650:G:GG	acceptor_gain	1.0000
11:1075650:GA:G	acceptor_gain	1.0000
11:1075650:GAG:G	acceptor_gain	1.0000
11:1075650:GAGG:G	acceptor_gain	1.0000
11:1075872:G:GT	donor_gain	1.0000
11:1075917:GCCGT:G	donor_gain	1.0000
11:1075920:GT:G	donor_gain	1.0000
11:1075922:G:GG	donor_gain	1.0000
11:1077557:G:GT	donor_gain	1.0000
11:1077950:A:AG	acceptor_gain	1.0000
11:1077950:AGCT:A	acceptor_gain	1.0000
11:1077950:AGCTG:A	acceptor_gain	1.0000
11:1077951:G:GA	acceptor_gain	1.0000
11:1077951:GCT:G	acceptor_gain	1.0000
11:1077951:GCTG:G	acceptor_gain	1.0000
11:1077951:GCTGG:G	acceptor_gain	1.0000
11:1078039:GACG:G	donor_gain	1.0000
11:1078040:ACGG:A	donor_loss	1.0000
11:1078041:CGGT:C	donor_loss	1.0000
11:1078043:G:GA	donor_loss	1.0000
11:1078043:G:GG	donor_gain	1.0000
11:1078044:T:A	donor_loss	1.0000
11:1078120:CAG:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000022774 (11:1103517 C>T), RS1000072343 (11:1099952 A>C,G,T), RS1000150810 (11:1106218 A>G), RS1000183864 (11:1105718 G>A,C), RS1000249882 (11:1090164 T>C), RS1000684221 (11:1076174 C>T), RS1000812145 (11:1110591 G>A,T), RS1000943840 (11:1090697 G>A), RS1000987016 (11:1100453 C>T), RS1001081744 (11:1100579 G>A,C), RS1001436155 (11:1108806 G>C), RS1001482200 (11:1110427 C>G), RS1001584905 (11:1074973 G>A,C), RS1001596343 (11:1105376 T>G), RS1001750466 (11:1074754 C>T)

Disease associations

OMIM: gene MIM:158370 | disease phenotypes: MIM:256730

GenCC curated gene-disease

Mondo (1): neuronal ceroid lipofuscinosis (MONDO:0016295)

Orphanet (2): Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001968_6	Interstitial lung disease	7.000000e-34
GCST007798_126	Asthma	4.000000e-12
GCST007799_29	Asthma (adult onset)	3.000000e-12
GCST007941_10	Medication use (adrenergics, inhalants)	3.000000e-10
GCST009720_50	Asthma	1.000000e-09
GCST009798_52	Asthma	2.000000e-10
GCST010042_52	Asthma	3.000000e-15
GCST010043_45	Asthma	2.000000e-18
GCST90014325_18	Asthma	4.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1002011	adult onset asthma
EFO:0009941	Inhalant adrenergic use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, affects expression	3
Benzo(a)pyrene	affects methylation	2
nicotinate mononucleotide	increases expression	1
bisphenol A	decreases secretion, decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	increases expression	1
nicotinic acid adenine dinucleotide	increases expression	1
4-hydroxyretinoic acid	increases expression	1
ochratoxin A	affects cotreatment, decreases secretion, increases expression, decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
cupric oxide	increases expression	1
puag-haad	decreases reaction, increases expression	1
4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)benzoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
bisphenol B	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Troglitazone	increases expression	1
Eucalyptol	decreases reaction, increases expression	1
Amphotericin B	increases expression	1
Arsenic	decreases expression	1
Carmustine	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	decreases reaction, increases expression	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00337636	PHASE1	COMPLETED	Study of HuCNS-SC Cells in Patients With Infantile or Late Infantile Neuronal Ceroid Lipofuscinosis (NCL)
NCT01238315	PHASE1	WITHDRAWN	Safety and Efficacy Study of HuCNS-SC in Subjects With Neuronal Ceroid Lipofuscinosis
NCT07582484	PHASE1/PHASE2	NOT_YET_RECRUITING	Gene Therapy Trial for CLN6 Batten Disease
NCT01873924	Not specified	RECRUITING	Clinical and Neuropsychological Investigations in Batten Disease
NCT01966757	Not specified	COMPLETED	Neuronal Ceroid Lipofuscinosis and Associated Sleep Abnormalities
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
NCT06844877	Not specified	RECRUITING	Italian NCL Registry: a Registry for NCL as an Integration Tool for Future Therapeutic Strategies