MUC4

Summary

MUC4 (mucin 4, cell surface associated, HGNC:7514) is a protein-coding gene on chromosome 3q29, encoding Mucin-4 (Q99102). Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces.

The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats.

Source: NCBI Gene 4585 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 406 total
• MANE Select transcript: NM_018406

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7514
Approved symbol	MUC4
Name	mucin 4, cell surface associated
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	ASGP, MUC-4
Ensembl gene	ENSG00000145113
Ensembl biotype	protein_coding
OMIM	158372
Entrez	4585

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 13 nonsense_mediated_decay, 4 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000308466, ENST00000339251, ENST00000346145, ENST00000349607, ENST00000392407, ENST00000415455, ENST00000448861, ENST00000462323, ENST00000463781, ENST00000464234, ENST00000466475, ENST00000467235, ENST00000469992, ENST00000470451, ENST00000475231, ENST00000477086, ENST00000477756, ENST00000478156, ENST00000478685, ENST00000479406, ENST00000480843, ENST00000486425

RefSeq mRNA: 3 — MANE Select: NM_018406 NM_004532, NM_018406, NM_138297

CCDS: CCDS3310, CCDS3311, CCDS54700

Canonical transcript exons

ENST00000463781 — 25 exons

Exon	Start	End
ENSE00001271706	195778303	195778455
ENSE00001799179	195811736	195811929
ENSE00001854802	195778790	195791497
ENSE00003476269	195764997	195765122
ENSE00003476365	195764045	195764164
ENSE00003490189	195763433	195763641
ENSE00003553048	195769022	195769152
ENSE00003554694	195762855	195762945
ENSE00003574671	195760884	195761117
ENSE00003582400	195748902	195749064
ENSE00003590287	195753051	195753230
ENSE00003591130	195765270	195765449
ENSE00003613726	195750889	195751112
ENSE00003627991	195752373	195752446
ENSE00003634886	195771652	195771816
ENSE00003637835	195766663	195766751
ENSE00003649518	195770216	195770371
ENSE00003657258	195774172	195774305
ENSE00003659654	195759124	195759261
ENSE00003663571	195754213	195754372
ENSE00003666016	195751207	195751271
ENSE00003672632	195761484	195761585
ENSE00003674901	195762087	195762254
ENSE00003689558	195757147	195757328
ENSE00003845804	195746771	195747380

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 97.62.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7731 / max 355.4950, expressed in 196 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46305	2.0715	177
46302	0.3816	74
46303	0.1361	53
46306	0.1075	42
46304	0.0765	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	97.62	gold quality
nasal cavity epithelium	UBERON:0005384	96.98	gold quality
mucosa of transverse colon	UBERON:0004991	96.54	gold quality
palpebral conjunctiva	UBERON:0001812	96.52	gold quality
epithelium of nasopharynx	UBERON:0001951	96.16	gold quality
nasopharynx	UBERON:0001728	96.14	gold quality
bronchial epithelial cell	CL:0002328	94.93	gold quality
epithelium of bronchus	UBERON:0002031	94.91	gold quality
bronchus	UBERON:0002185	94.80	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.73	gold quality
pharyngeal mucosa	UBERON:0000355	94.16	gold quality
colonic mucosa	UBERON:0000317	93.26	gold quality
urethra	UBERON:0000057	93.14	gold quality
rectum	UBERON:0001052	92.93	gold quality
lower esophagus mucosa	UBERON:0035834	92.86	gold quality
trachea	UBERON:0003126	92.17	gold quality
nasal cavity mucosa	UBERON:0001826	91.26	gold quality
transverse colon	UBERON:0001157	90.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.66	gold quality
colonic epithelium	UBERON:0000397	88.95	gold quality
esophagus mucosa	UBERON:0002469	86.50	gold quality
ileal mucosa	UBERON:0000331	85.05	gold quality
oral cavity	UBERON:0000167	84.80	gold quality
eye	UBERON:0000970	84.04	gold quality
minor salivary gland	UBERON:0001830	83.56	gold quality
buccal mucosa cell	CL:0002336	82.98	gold quality
esophagus squamous epithelium	UBERON:0006920	82.03	gold quality
large intestine	UBERON:0000059	81.46	gold quality
colon	UBERON:0001155	81.05	gold quality
vagina	UBERON:0000996	80.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	43.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, E2F1, ELF5, ELK1, ETS1, ETV1, ETV4, ETV5, FOXA1, FOXA2, GATA5, HAND2, HNF1A, HNF4A, JUN, NR3C1, RARA, SMAD2, SMAD4, SMAD7, SP1, SP3, STAT1, STAT3, TFAP2A, TFAP4, YY1

miRNA regulators (miRDB)

21 targeting MUC4, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-924	97.78	66.21	681
HSA-MIR-147B-3P	94.55	64.40	94
HSA-MIR-1296-5P	93.94	67.71	305

Literature-anchored findings (GeneRIF, showing 40)

• expression is increased in dysplastic cervical disorders (PMID:11727258)
• the genomic structure of the 3’ region of the human MUC4 gene was determined. Our results show that it spans approximately 30.8 kb of genomic DNA and is composed of 24 exons, including one alternative exon (PMID:12153560)
• induces the phosphorylation of ErbB2 to enhance the tyrosine phosphate epitope (Tyr1248) recognized by anti-phospho-ErbB2 (PMID:12386815)
• airway epithelial cells respond to neutrophil elastase exposure by increasing expression of MUC4, a potential activator of epithelial repair mechanisms. (PMID:12495942)
• although Muc4(+) cells express less MDR1 and MRP1, they are more resistant to drugs recognized by these transporters. (PMID:12732353)
• MUC4 has an important role in regulating ErbB2 signaling (PMID:12748185)
• MUC5B and MUC4 were major mucins in MOM that formed distinct treelike polymers (mucus strands)in the middle ear mucosa with mucoid otitis media (PMID:14690056)
• Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis (PMID:14744777)
• MUC4 protein is associated with the metastatic pancreatic cancer phenotype and plays a role in altered growth and behavioral properties of the tumor cell. (PMID:14744777)
• upregulation of MUC4 by TGF-beta is restricted to well-differentiated pancreatic cancer cells, and point out a novel mechanism for TGF-beta as a key molecule in targeting MUC4 overexpression in pancreatic adenocarcinomas. (PMID:15184872)
• PEA3 is a transactivator of the MUC4 promoter. The -216 and -2368 PEA3 binding sites of the MUC4 promoter are essential. (PMID:15461591)
• As a luminal surface component, the MUC4 is situated to contribute to the non-adhesive luminal surface and to act as an intrinsic protection and survival factor for blood vessels (PMID:15672420)
• MUC4 expression is related to a better prognosis in mucoepidermoid carcinomas of the salivary glands. (PMID:15897748)
• Synergistic induction of the MUC4 mucin gene by interferon-gamma and retinoic acid in human pancreatic tumour cells involves a reprogramming of signalling pathways. Oncogene (PMID:16007204)
• findings provide potential mechanisms that may account for aberrant expression of MUC4 in pancreatic tumour cells (PMID:16007204)
• Analysis of the ability of human milk to inhibit the attachment of rNV VLPs (recombinant NV-like particles) to their carbohydrate ligands and to characterize potential inhibitors found in milk is presented. (PMID:16266293)
• MUC4 is significantly down regulated in prostate cancer (PMID:16302265)
• Here we provide evidence that the cleavage step of Muc4/SMC processing occurs by a proteolytic mechanism. First, processing of Muc4/SMC precursor to ASGP-2 was inhibited in the presence of the mechanism-based serine protease inhibitor, Pefabloc SC (PMID:16329125)
• Overexpresssed in the progression and lymphatic metastasis of prostate cancer. (PMID:16475027)
• The ability of Muc4 to segregate ErbB2 and other ErbB receptors and to alter downstream signaling cascades in polarized epithelial cells suggests that it has a role in regulating ErbB2 in differentiated epithelia. (PMID:16624867)
• Muc4 potentiates neuregulin signaling by increasing the cell-surface populations of ErbB2 and ErbB3 (PMID:16690615)
• IL-9 modulated MUC4 mucin in airway epithelial tumor cells. (PMID:16779668)
• Downregulation of CFTR in pancreatic adenocarcinoma and its inverse association with the tumour-linked mucin, MUC4, indicate novel function(s) of CFTR in pancreatic tumour biology and suggest the implication of new signalling pathway(s) in MUC4 regulation (PMID:16799633)
• MUC4 expression is regulated by cystic fibrosis transmembrane conductance regulator in pancreatic adenocarcinoma cells via transcriptional and post-translational mechanisms (PMID:16799633)
• MUC4 expression is not directly regulated by steroids in women and its polymorphism does not have a role in implantation failure (PMID:16807280)
• MUC4 may have a role in progression of extrahepatic bile duct carcinoma (PMID:16857800)
• MUC4 showed significant overexpression in tumor cases (P<0.0001) with highest incidence (92.0%) among all three mucins. (PMID:16880776)
• Muc4 induces density-dependent changes in ERK activation in mammary epithelial and tumor cells (PMID:16891313)
• regulation of MUC4 expression by bile acids, in which HNF1alpha is a key mediator. These results bring new insights into MUC4 up-regulation in oesophageal carcinoma associated with bile reflux. (PMID:17037983)
• Aberrant intestinal expression and allelic variant MUC4 is associated with inflammatory bowel disease. (PMID:17058067)
• Inhibition of expression of Muc4 at the cell surface blocked phosphorylation of ErbB3 in a signet ring carcinoma cell line. (PMID:17292332)
• In conclusion, our study provides experimental evidence that supports the functional significance of MUC4 in pancreatic cancer progression and indicates a novel role for MUC4 in cancer cell signaling. (PMID:17406026)
• MUC4 is regulated at the transcriptional level by CDX-1 and -2, HNF-1 alpha and -1 beta, FOXA1/A2, HNF-4 alpha and -4 gamma, and GATA-4, -5, and -6 factors in a cell-specific manner (PMID:17553805)
• This study shows that MUC1, MUC4, and MUC16 are regulated differently by dexamethasone in human corneal epithelial cells. (PMID:17592322)
• is negatively regulated in pancreatic tissue by AP-2A (PMID:17621592)
• MUC4 gene is expressed in the nasal polyps and that glucocorticoid can control the expression of the MUC4 gene and mucin glycoprotein synthesis. (PMID:17891050)
• MUC4 is an excellent marker for differentiating ovarian/primary peritoneal serous carcinoma from both benign and malignant mesothelial cells. (PMID:18008338)
• The interaction of human MUC4 with the receptor tyrosine kinase HER2 in pancreatic adenocarcinoma cells is showm by reciprocal coimmunoprecipitation and cocapping studies. (PMID:18381409)
• findings suggest that MUC4 is up-regulated and interacts with erbB2 in human gallbladder carcinoma, and thereby support the potential implication of MUC4 in erbB2 activation. (PMID:18397823)
• Biliary MUC4 is a highly specific tumour-associated mucin that may be useful in the diagnosis and formulation of therapeutic strategies in biliary tract cancer (BTC). (PMID:18475301)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch73-105b23.6	ENSDARG00000087190
mus_musculus	Muc4	ENSMUSG00000118672
rattus_norvegicus		ENSRNOG00000089703
drosophila_melanogaster	mesh	FBGN0051004
caenorhabditis_elegans		WBGENE00010047
caenorhabditis_elegans		WBGENE00010540
caenorhabditis_elegans		WBGENE00011175

Paralogs (2): SUSD2 (ENSG00000099994), RTL9 (ENSG00000243978)

Protein

Protein identifiers

Mucin-4 — Q99102 (reviewed: Q99102)

Alternative names: Ascites sialoglycoprotein, Pancreatic adenocarcinoma mucin, Testis mucin, Tracheobronchial mucin

All UniProt accessions (13): E7ENC5, E7EQG8, E7EQT2, E7ERK0, E7ETT5, E7EUL9, E7EW47, E7EWN1, E9PDY6, Q99102, H0Y2Y1, H7BXN7, H7BZI3

UniProt curated annotations — full annotation on UniProt →

Function. Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces. These glycoproteins play important roles in the protection of the epithelium and are implicated in epithelial renewal and differentiation. Regulates cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and its ability to act as an intramembrane ligand for ERBB2. Plays an important role in proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. In polarized epithelial cells, segregates ERBB2 and other ERBB receptors and prevents ERBB2 from acting as a coreceptor. The interaction with ERBB2 leads to enhanced expression of CDKN1B. The formation of a MUC4-ERBB2-ERBB3-NRG1 complex leads to down-regulation of CDKN1B, resulting in repression of apoptosis and stimulation of proliferation. Its ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation.

Subunit / interactions. A heterodimeric complex, composed of a mucin-4 alpha chain and a cysteine-rich transmembrane mucin-4 beta chain. Mucin-4 beta chain interacts with ERBB2 via the EGF-like domain 1. In nonpolarized cells, associates with ERBB2 and ERBB3.

Subcellular location. Cell membrane Cell membrane. Secreted Cell membrane Secreted Secreted Cell membrane.

Tissue specificity. Expressed in the thymus, thyroid, lung, trachea, esophagus, stomach, small intestine, colon, testis, prostate, ovary, uterus, placenta, and mammary and salivary glands. Expressed in carcinomas arising from some of these epithelia, such as lung cancers, squamous cell carcinomas of the upper aerodigestive tract, mammary carcinomas, biliary tract, colon, and cervix cancers. Minimally or not expressed in the normal pancreas or chronic pancreatitis, but is highly expressed in pancreatic tumors and pancreatic tumor cell lines.

Post-translational modifications. Proteolytically cleaved into 2 chains, mucin-4 alpha chain and mucin-4 beta chain. Highly O-glycosylated. Is predominantly N-glycosylated.

Domain organisation. Essentially composed of an array of serine- and threonine-rich tandem repeats which is highly polymorphic, the variable number of tandem repeats (VNTR) region.

Polymorphism. The variable number of tandem repeats (VNTR) region, an array of serine- and threonine-rich tandem repeats, is encoded by a single exon (exon 2) which is highly polymorphic.

Miscellaneous. Expression is a very useful predictor of poor prognosis in patients with invasive ductal carcinoma and intrahepatic cholangiocarcinoma, mass forming type (IDC,ICC-MF). Patients with IDC or ICC-MF who have high MUC4 expression had a worse survival rate than those with low MUC4 expression. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Dubious isoform produced through aberrant splice sites. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be preferentially expressed in tumor tissues. May be preferentially expressed in tumor tissues. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Dubious isoform produced through aberrant splice sites. Dubious isoform produced through aberrant splice sites.

Isoforms (14)

UniProt ID	Names	Canonical?
Q99102-1	1, Sv0-MUC4, Sv21	yes
Q99102-2	2, Sv3-MUC4, Sv4-MUC4, Sv5-MUC4, Sv12, Sv13
Q99102-3	3, Sv20, sv7-MUC4
Q99102-5	5, Sv18, Sv19
Q99102-7	7, Sv16
Q99102-8	8, Sv15
Q99102-9	9, Sv11
Q99102-10	10, Sv3, Sv17, Sv10
Q99102-11	11, Sv2, Sv9, Sv14
Q99102-12	12, SvX, MUC4/X
Q99102-13	13, SvY, MUC4/Y
Q99102-15	15, Sv1
Q99102-16	16, Sv6-MUC4
Q99102-17	17, Sv8-MUC4

RefSeq proteins (3): NP_004523, NP_060876, NP_612154 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR001846	VWF_type-D	Domain
IPR003886	NIDO_dom	Domain
IPR005533	AMOP_dom	Domain
IPR051495	Epithelial_Barrier/Signaling	Family
IPR056619	C8-3_MUC4	Domain

Pfam: PF00094, PF06119, PF23263

UniProt features (766 total): glycosylation site 547, compositionally biased region 133, splice variant 22, region of interest 20, sequence conflict 19, sequence variant 8, disulfide bond 6, domain 5, chain 3, signal peptide 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q99102 — 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): 4687–4688 (cleavage)

Disulfide bonds (6): 5122–5133, 5127–5145, 5147–5156, 5324–5335, 5329–5344, 5346–5359

Glycosylation sites (547): 154, 156, 230, 234, 255, 364, 369, 376, 617, 620, 666, 688, 747, 797, 798, 802, 804, 813, 814, 881 …

Function

Pathways and Gene Ontology

Reactome pathways

16 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
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

MSigDB gene sets: 124 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_DIGESTION, REACTOME_INNATE_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, CACCAGC_MIR138, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, CAGCAGG_MIR370, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_MAINTENANCE_OF_GASTROINTESTINAL_EPITHELIUM, NAKAMURA_LUNG_CANCER_DIFFERENTIATION_MARKERS, GOBP_DIGESTIVE_SYSTEM_PROCESS, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, MODULE_544

GO Biological Process (3): cell-matrix adhesion (GO:0007160), maintenance of gastrointestinal epithelium (GO:0030277), cell adhesion (GO:0007155)

GO Molecular Function (2): ErbB-2 class receptor binding (GO:0005176), extracellular matrix constituent, lubricant activity (GO:0030197)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular matrix (GO:0031012), vesicle (GO:0031982), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-11 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
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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell-substrate adhesion	1
epithelial structure maintenance	1
digestive system process	1
cellular process	1
signaling receptor binding	1
extracellular matrix structural constituent	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
external encapsulating structure	1
membrane-bounded organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

2292 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MUC4	ERBB2	P04626	993
MUC4	MUC1	P13931	979
MUC4	MUC20	Q8N307	948
MUC4	MUC2	Q02817	938
MUC4	MUC16	Q8WXI7	930
MUC4	MUC13	Q9H3R2	923
MUC4	ERBB3	P21860	886
MUC4	MUC15	Q8N387	846
MUC4	EGFR	P00533	839
MUC4	MUC6	Q6W4X9	825
MUC4	ISM2	Q6H9L7	809
MUC4	MUC7	Q8TAX7	798
MUC4	MUC21	Q5SSG8	781
MUC4	MUC22	E2RYF6	701
MUC4	MUC19	Q7Z5P9	696

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MUC4		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): MUC4 (Affinity Capture-MS), MUC4 (Affinity Capture-MS), MUC4 (Two-hybrid), MUC4 (Two-hybrid), MUC4 (Two-hybrid), MUC4 (Two-hybrid), MUC4 (Two-hybrid), MUC4 (Affinity Capture-Western), ERBB2 (Affinity Capture-Western), MUC4 (Affinity Capture-MS), MUC4 (Affinity Capture-MS), MUC4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUW6, A1EGX6, A6NM11, A6NMS7, A6QLF8, D3YU32, I3L273, J3KML8, O35930, O60309, Q08DY0, Q14242, Q2TBI7, Q32KG4, Q32L62, Q3MIW9, Q3TNW5, Q3V0E1, Q4R729, Q5VWK0, Q5VYM1, Q62170, Q659K0, Q68DN1, Q6AZ54, Q6MG22, Q6UXB8, Q6ZRG5, Q8BUE7, Q8K4E0, Q8N307, Q8N3K9, Q8TCU4, Q8WNU4, Q8WXI7, Q95JY5, Q96F05, Q96JA4, Q96M34, Q96M43

Diamond homologs: Q63661, Q8JZM8, Q99102, B5DFC9, O08523, O75443, O88322, Q14112, Q9DBX3, Q9UGT4, Q9YH85

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CREB1	“up-regulates quantity by expression”	MUC4	“transcriptional regulation”
ELK1	“up-regulates quantity by expression”	MUC4	“transcriptional regulation”
ETS1	“up-regulates quantity by expression”	MUC4	“transcriptional regulation”
STAT1	“up-regulates quantity by expression”	MUC4	“transcriptional regulation”
E2F1	“up-regulates quantity by expression”	MUC4	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	211
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

4549 predictions. Top by Δscore:

Variant	Effect	Δscore
3:195747389:C:CT	acceptor_gain	1.0000
3:195747390:A:T	acceptor_gain	1.0000
3:195748961:A:AC	donor_gain	1.0000
3:195748962:C:CC	donor_gain	1.0000
3:195750054:AG:A	donor_gain	1.0000
3:195750883:A:AC	donor_gain	1.0000
3:195750884:C:CC	donor_gain	1.0000
3:195750887:A:AC	donor_gain	1.0000
3:195750887:ACGGG:A	donor_gain	1.0000
3:195750888:C:CC	donor_gain	1.0000
3:195750888:CGGG:C	donor_gain	1.0000
3:195750888:CGGGC:C	donor_gain	1.0000
3:195751110:TCG:T	acceptor_gain	1.0000
3:195751111:CG:C	acceptor_gain	1.0000
3:195751111:CGC:C	acceptor_gain	1.0000
3:195751113:C:CC	acceptor_gain	1.0000
3:195751205:A:AC	donor_gain	1.0000
3:195751206:C:CC	donor_gain	1.0000
3:195751206:CATT:C	donor_gain	1.0000
3:195757335:C:T	acceptor_gain	1.0000
3:195759119:CCTA:C	donor_loss	1.0000
3:195759120:CTA:C	donor_loss	1.0000
3:195759121:TA:T	donor_loss	1.0000
3:195759122:A:AC	donor_gain	1.0000
3:195759122:A:T	donor_loss	1.0000
3:195759123:C:CA	donor_loss	1.0000
3:195759123:C:CC	donor_gain	1.0000
3:195759257:CTGAT:C	acceptor_gain	1.0000
3:195759258:TGAT:T	acceptor_gain	1.0000
3:195759260:AT:A	acceptor_gain	1.0000

AlphaMissense

33855 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000109363 (3:195808375 C>G), RS1000113465 (3:195794277 CTT>C,CT,CTTT), RS1000156433 (3:195810046 C>T), RS1000178223 (3:195788787 G>A,C,T), RS1000338448 (3:195800346 A>G), RS1000348467 (3:195774672 C>A,G,T), RS1000376370 (3:195805255 G>A,C), RS1000381034 (3:195758037 C>G,T), RS1000402386 (3:195810274 A>C), RS1000512364 (3:195766895 A>C,G,T), RS1000517372 (3:195813791 G>T), RS1000558466 (3:195757466 G>C), RS1000578826 (3:195768388 G>A), RS1000627450 (3:195773526 C>T), RS1000718135 (3:195752053 C>T)

Disease associations

OMIM: gene MIM:158372 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 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
GCST004379_2	Red blood cell density in sickle cell anemia	7.000000e-07
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	8
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	6
trichostatin A	increases expression, affects cotreatment	4
Tobacco Smoke Pollution	affects expression, decreases expression	3
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Vehicle Emissions	decreases reaction, increases expression, increases abundance	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
Phthalic Acids	increases abundance, increases methylation	2
aristolochic acid I	increases expression	1
hempseed oil	affects cotreatment, decreases secretion	1
glycidyl methacrylate	decreases expression	1
titanium dioxide	increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
Ro 41-5253	increases reaction, decreases reaction, increases expression	1
SB 203580	decreases reaction, 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
abrine	increases expression	1
necrostatin-1	decreases reaction, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
10-(6’-plastoquinonyl)decyltriphenylphosphonium	decreases expression, decreases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Dust	increases expression	1
Estradiol	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D6AN	HyCyte A-549 KO-hMUC4	Cancer cell line	Male

Clinical trials (associated diseases)

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