MUC5AC

Summary

MUC5AC (mucin 5AC, oligomeric mucus/gel-forming, HGNC:7515) is a protein-coding gene on chromosome 11p15.5, encoding Mucin-5AC (P98088). Gel-forming glycoprotein of gastric and respiratory tract epithelia that protects the mucosa from infection and chemical damage by binding to inhaled microorganisms and particles that are subsequently removed by the mucociliary system.

Predicted to enable extracellular matrix constituent, lubricant activity. Predicted to be an extracellular matrix structural constituent. Predicted to act upstream of or within maintenance of lens transparency. Located in extracellular space and mucus layer. Implicated in dry eye syndrome. Biomarker of several diseases, including Sjogren’s syndrome; biliary tract disease (multiple); cystic fibrosis; eye disease (multiple); and pancreatic cancer (multiple).

Source: NCBI Gene 4586 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 38 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_001304359

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7515
Approved symbol	MUC5AC
Name	mucin 5AC, oligomeric mucus/gel-forming
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	MUC5
Ensembl gene	ENSG00000215182
Ensembl biotype	protein_coding
OMIM	158373
Entrez	4586

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000621226

RefSeq mRNA: 1 — MANE Select: NM_001304359 NM_001304359

CCDS: CCDS76369

Canonical transcript exons

ENST00000621226 — 49 exons

Exon	Start	End
ENSE00002159139	1157953	1158072
ENSE00002218664	1168483	1168552
ENSE00002220702	1164407	1164532
ENSE00002232538	1168642	1168779
ENSE00002242603	1163882	1163991
ENSE00002248521	1168862	1169026
ENSE00002253970	1161907	1162168
ENSE00002282058	1167877	1167987
ENSE00002298111	1164106	1164319
ENSE00002306710	1161527	1161586
ENSE00002309852	1162532	1162646
ENSE00002310419	1165622	1165760
ENSE00002310438	1162955	1163045
ENSE00002313711	1165302	1165419
ENSE00002316814	1160612	1160689
ENSE00003711854	1195012	1195279
ENSE00003712771	1199087	1199185
ENSE00003719499	1195876	1196054
ENSE00003722197	1194110	1194360
ENSE00003722780	1196877	1196908
ENSE00003723583	1199855	1199969
ENSE00003725928	1196617	1196720
ENSE00003729686	1198268	1198305
ENSE00003730163	1199371	1199490
ENSE00003731072	1197903	1198004
ENSE00003735077	1197468	1197639
ENSE00003735509	1198874	1198996
ENSE00003736454	1193485	1193659
ENSE00003738794	1194487	1194670
ENSE00003740635	1200438	1201138
ENSE00003741883	1199695	1199764
ENSE00003748190	1196388	1196475
ENSE00003751568	1192783	1192982
ENSE00003751810	1182155	1192525
ENSE00003755089	1176928	1177066
ENSE00003755905	1181139	1181182
ENSE00003756047	1176151	1176251
ENSE00003756139	1181271	1181459
ENSE00003756332	1179092	1179248
ENSE00003756363	1172429	1172523
ENSE00003756790	1180354	1180516
ENSE00003757319	1176514	1176665
ENSE00003757351	1178444	1178683
ENSE00003757516	1174882	1175137
ENSE00003758201	1174496	1174622
ENSE00003759016	1180022	1180150
ENSE00003759096	1177231	1177344
ENSE00003760014	1175218	1175270
ENSE00003760106	1177454	1177633

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 95.13.

FANTOM5 (CAGE): breadth broad, TPM avg 11.7972 / max 9319.1327, expressed in 243 samples.

FANTOM5 promoters (24 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112376	8.0302	208
206131	1.0389	142
206118	0.6511	117
206123	0.2435	65
206121	0.1944	55
206124	0.1855	54
206133	0.1796	47
206128	0.1722	46
206120	0.1465	39
206119	0.1284	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	95.13	gold quality
mucosa of stomach	UBERON:0001199	92.77	gold quality
body of stomach	UBERON:0001161	86.68	gold quality
stomach	UBERON:0000945	86.56	gold quality
fundus of stomach	UBERON:0001160	77.54	gold quality
gall bladder	UBERON:0002110	67.60	gold quality
colonic epithelium	UBERON:0000397	56.28	gold quality
bone marrow cell	CL:0002092	55.09	gold quality
endocervix	UBERON:0000458	53.39	gold quality
sural nerve	UBERON:0015488	50.85	gold quality
islet of Langerhans	UBERON:0000006	48.10	gold quality
duodenum	UBERON:0002114	45.94	silver quality
uterine cervix	UBERON:0000002	45.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.66	gold quality
vermiform appendix	UBERON:0001154	43.48	gold quality
urinary bladder	UBERON:0001255	43.21	silver quality
skeletal muscle tissue	UBERON:0001134	42.70	gold quality
pancreas	UBERON:0001264	42.43	gold quality
muscle tissue	UBERON:0002385	42.06	gold quality
tonsil	UBERON:0002372	41.61	gold quality
bone marrow	UBERON:0002371	41.41	gold quality
right lung	UBERON:0002167	41.15	silver quality
rectum	UBERON:0001052	40.20	gold quality
superior frontal gyrus	UBERON:0002661	39.93	gold quality
leukocyte	CL:0000738	39.15	gold quality
monocyte	CL:0000576	38.72	gold quality
stromal cell of endometrium	CL:0002255	38.59	gold quality
lower esophagus mucosa	UBERON:0035834	38.51	gold quality
lung	UBERON:0002048	38.18	gold quality
body of pancreas	UBERON:0001150	38.02	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATOH1, CREB1, CTCF, DNMT1, ETS1, GLI1, GLI2, HDAC2, HES1, HIF1A, JUN, NFE2L2, NFKB1, NFKB, NFKBID, NR3C1, NR4A3, PPARG, RARA, RELA, SMAD4, SOX2, SP1, SP3, ZFHX3, ZHX2

miRNA regulators (miRDB)

15 targeting MUC5AC, 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-4673	100.00	66.64	1490
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-6847-5P	97.93	66.74	1808

Literature-anchored findings (GeneRIF, showing 40)

• Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species (PMID:11919081)
• Gastric MUC5AC and MUC6 are large oligomeric mucins that differ in size, glycosylation and tissue distribution (PMID:11988092)
• Mapping of two new epitopes on the apomucin encoded by MUC5AC gene: expression in normal GI tract and colon tumors. (PMID:11992401)
• Overexpression of MUC5AC induced by interleukin-1 beta, tumor necrosis factor-alpha, lipopolysaccharide, and neutrophil elastase is inhibited by a retinoic acid receptor alpha antagonist. (PMID:12042033)
• Aberrant expression of MUC5AC and MUC6 gastric mucins and sialyl Tn antigen in intraepithelial neoplasms of the pancreas. (PMID:12360467)
• 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)
• A significant reduction of gastric differentiation as reflected by MUC5AC immunoreactivity represents a marker of worse survival probability in gastric cancer. Finally, reduced MUC5AC positivity defines a high-risk subgroup of pTNM stage I patients. (PMID:12417511)
• The expression of MUC5AC in pancreatic cancer cell lines may involve additional regions or other mechanisms than proximal promoter methylation. (PMID:12527922)
• FUT1 catalyses the addition of alpha-1,2-fucose to MUC1 and MUC5AC apomucins (PMID:12652076)
• IL1beta and TNFalpha activation of MSK1 and CREB and cAMP-response element signaling cascades occurs via ERK/p38 MAP kinases and are crucial aspects of the intracellular mechanisms that mediate MUC5AC gene expression (PMID:12690113)
• There was no correlation of MUC2 or MUC5AC mucin with polyp size or the grade of dysplasia using the non-VNTR antibodies (PMID:12820724)
• expression is meadiated by tumor necrosis factor alpha-converting enzyme in cultured airway cells (PMID:12972643)
• IL-1beta, in a dose- and time-dependent manner, increased the secretion of MUC5AC, but not MUC5B in bronchial epithelium (PMID:14527933)
• Mucin MUC5AC is the most important carrier of the LeB carbohydrate structure in normal gastric tissue and forms the major receptor for H. pylori. (PMID:14535999)
• identification of five major intracellular populations of the MUC5AC polypeptide (unglycosylated monomer and dimer, GalNAc-substituted dimer, fully glycosylated dimer, and higher order oligomers) (PMID:14749330)
• The concentration of MUC5AC and MUC5B are decreased in the CF airways relative to normal mucus. This may be due to a relative increase in other components of sputum in the CF airway or to a primary defect in mucin secretion in CF. (PMID:14988081)
• MUC5AC expression plays an important role in impacting tumor progression in invasive ductal carcinoma of the pancreas; its expression is associated with increased survival (PMID:15235131)
• Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation (PMID:15531749)
• There were significant differences were found in the glycosylation of MUC5B/MUC5AC or gp-340 between CF and non-CF subjects with severe lung disease, implying that CF does not influence SMG secretion mucin glycosylation in end-stage lung disease. (PMID:15563276)
• hypothesis that Duox1 activates TACE, cleaving pro-TGF-alpha into soluble TGF-alpha, resulting in MUC5AC mucin expression is examined and supported (PMID:15640347)
• 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)
• TFF1, TFF2, TFF3 and MUC5AC may have roles in pathogenesis of pterygium goblet cells (PMID:16142316)
• HNE activates TACE via ROS generation, resulting in cleavage of pro-TGF-alpha, EGFR activation, and MUC5AC mucin expression in airway epithelial cells (PMID:16148149)
• MUC1, MUC5B and MUC8, but not MUC2 or MUC5AC, are up-regulated in endometrial adenocarcinomas (PMID:16188033)
• Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression were thought to be important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease. (PMID:16251127)
• Decreased survival in colorectal carcinoma patients with MUC5AC antibody positivity may be due to a decrease in the MUC5AC expression in tumor tissues of surviving carcinoma patients. (PMID:16409634)
• IL-13 might induce the expression of MUC5AC and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might also differentiate into goblet cells and become hyperplastic. (PMID:16465045)
• Overexpresssed in the progression and lymphatic metastasis of prostate cancer. (PMID:16475027)
• This is the first reliable investigation of the regulation of MUC5AC mucin secretion by silencing AQP5. (PMID:16500622)
• MUC5AC/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA ratios in the study group was significantly increased compared with those in both control groups (P < .05). (PMID:16540890)
• The expression of MUC5AC increased with the progression of lesions in pancreatic carcinoma. (PMID:16552336)
• Increased MUC5AC is associated with the pancreatobiliary phenotype of ampulla of vater carcinoma and involved in later events in carcinogenesis, such as invasion and metastasis (PMID:16596179)
• MUC5AC is preferentially expressed in intraductal papillary mucinous adenomas than in mucinous cystdenomas. (PMID:16722930)
• The cleavage of MUC5AC and the generation of the reactive new C-terminus could contribute to the adherent and viscous mucus found at chronic lung diseases, characterized by mucus hypersecretion and lowered pH of the airways. (PMID:16787389)
• An inflammation-dependent EGF-R cascade causes overproduction of the gel-forming mucin MUC5AC, which accumulates in cholesterol gallstone disease. The ability to interrupt this cascade is of potential interest in the prevention of cholesterol gallstones. (PMID:17148666)
• a decrease in MUC2 expression and staining of MUC5AC in non-goblet-like cells are observed in progression of preneoplastic lesions (PMID:17203232)
• Expressions of membrane (MUC1) and secreted (MUC5AC, MUC6) mucins are frequently modified in reactive gastropathy. (PMID:17227128)
• pneumolysin is required for up-regulation of MUC5AC mucin via TLR4-dependent activation of ERK1 in Streptococcus pneumoniae infections; IKK alpha and IKKbeta are distinctly involved in MUC5AC induction by S. pneumoniae via an ERK1-dependent mechanism (PMID:17237423)
• MUC5AC was isolated from an adenomatous colorectal neoplasm cell line and from gallbladder. The effect of chitinase on it was studied. (PMID:17321686)
• Results indicate that ATBF1 in the nucleus negatively regulates the MUC5AC gene in gastric cancer by binding to an AT motif-like element in the MUC5AC promoter. (PMID:17330845)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000109688
mus_musculus	Muc5ac	ENSMUSG00000037974
rattus_norvegicus	Muc5ac	ENSRNOG00000055996

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), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), FCGBP (ENSG00000275395)

Protein

Protein identifiers

Mucin-5AC — P98088 (reviewed: P98088)

Alternative names: Gastric mucin, Major airway glycoprotein, Mucin-5 subtype AC, tracheobronchial, Tracheobronchial mucin

All UniProt accessions (1): P98088

UniProt curated annotations — full annotation on UniProt →

Function. Gel-forming glycoprotein of gastric and respiratory tract epithelia that protects the mucosa from infection and chemical damage by binding to inhaled microorganisms and particles that are subsequently removed by the mucociliary system. Interacts with H.pylori in the gastric epithelium, Barrett’s esophagus as well as in gastric metaplasia of the duodenum (GMD).

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 from different CTCK-linked dimers to produce long, disulfide-linked polymers that remain highly compact until secretion.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in surface mucosal cells of respiratory tract and stomach epithelia. Overexpressed in a number of carcinomas. Also expressed in Barrett’s esophagus epithelium and in the proximal duodenum.

Post-translational modifications. C-, O- and N-glycosylated. O-glycosylated on the second and last Thr of the Thr-/Ser-rich tandem repeats TTPSPVPTTSTTSA. One form of glycosylation is also known as Lewis B (LeB) blood group antigen, a tetrasaccharide consisting of N-acetylglucosamine having a fucosyl residue attached. It has a role as an epitope and antigen and functions as a receptor for H.pylori binding and facilitates infection. C-mannosylation in the Cys-rich subdomains may be required for proper folding of these regions and for export from the endoplasmic reticulum during biosynthesis. Proteolytic cleavage in the C-terminal is initiated early in the secretory pathway and does not involve a serine protease. The extent of cleavage is increased in the acidic parts of the secretory pathway. Cleavage generates a reactive group which could link the protein to a primary amide.

Domain organisation. The cysteine residues in the Cys-rich subdomain repeats are not involved in disulfide bonding. The CTCK domain mediates interchain disulfide bonds with another molecule of MUC5AC.

Induction. By IL4.

RefSeq proteins (1): NP_001291288* (*=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, PF25962

UniProt features (366 total): strand 95, sequence conflict 74, glycosylation site 58, helix 34, compositionally biased region 23, turn 19, region of interest 17, disulfide bond 16, domain 12, repeat 9, binding site 3, mutagenesis site 2, signal peptide 1, chain 1, sequence variant 1, site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
5AJO	X-RAY DIFFRACTION	1.48
5AJP	X-RAY DIFFRACTION	1.65
5AJN	X-RAY DIFFRACTION	1.67
8OV0	X-RAY DIFFRACTION	1.7
8V9Q	X-RAY DIFFRACTION	2.29
8UI6	X-RAY DIFFRACTION	2.65
8UJF	X-RAY DIFFRACTION	2.87
9GVJ	ELECTRON MICROSCOPY	2.91
8QTB	ELECTRON MICROSCOPY	2.94
8R1U	ELECTRON MICROSCOPY	3.19
8R1Z	ELECTRON MICROSCOPY	3.2
8QTV	ELECTRON MICROSCOPY	3.25
8QSP	ELECTRON MICROSCOPY	3.69
9GVQ	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

No AlphaFold model available for P98088 — 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): 4926–4927 (cleavage)

Ligand- & substrate-binding residues (3): 198; 320; 367

Disulfide bonds (16): 81–211, 103–248, 434–571, 456–606, 478–486, 903–1036, 925–1071, 934–1033, 953–960, 4921–5063, 4943–5102, 4967–4975, 5532–5582, 5546–5596, 5557–5612, 5561–5614

Glycosylation sites (58): 4306, 4320, 4330, 4376, 4386, 4440, 4450, 4480, 4490, 4512, 4522, 4568, 4578, 4633, 4869, 4942, 5057, 5093, 5236, 5347 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
2122	no binding to mannose-specific lectin. loss of secretion from the endoplasmic reticulum.
4926	abolishes cleavage.

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: 67 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, WATANABE_COLON_CANCER_MSI_VS_MSS_UP, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, NUYTTEN_EZH2_TARGETS_DN, GOCC_GOLGI_LUMEN, NUYTTEN_NIPP1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, PEDRIOLI_MIR31_TARGETS_UP, CYCLIN_D1_KE_.V1_UP, CYCLIN_D1_UP.V1_UP, REACTOME_DISEASES_OF_GLYCOSYLATION, REACTOME_DISEASES_ASSOCIATED_WITH_O_GLYCOSYLATION_OF_PROTEINS

GO Biological Process (0):

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), mucus layer (GO:0070701), 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
structural molecule activity	1
extracellular matrix	1
cation binding	1
binding	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
external encapsulating structure	1
extracellular vesicle	1
extracellular region	1

Protein interactions and networks

STRING

2472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MUC5AC	MUC1	P13931	972
MUC5AC	MUC5B	Q9HC84	962
MUC5AC	MUC7	Q8TAX7	912
MUC5AC	MUC13	Q9H3R2	879
MUC5AC	MUC12	Q9UKN1	843
MUC5AC	MUC6	Q6W4X9	835
MUC5AC	MUC17	Q685J3	830
MUC5AC	MUC16	Q8WXI7	818
MUC5AC	MUC20	Q8N307	814
MUC5AC	TFF2	Q03403	807
MUC5AC	MUC19	Q7Z5P9	798
MUC5AC	IL13	P35225	795
MUC5AC	TFF3	Q07654	792
MUC5AC	MUC2	Q02817	785
MUC5AC	CD44	P16070	756

IntAct

15 interactions, top by confidence:

A	B	Type	Score
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
RIBC1	CNOT1	psi-mi:“MI:0914”(association)	0.530
INSR	HAX1	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
RASL11B	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
SLC5A1	CD63	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
FKBP14	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
TWF1	SERPINA3	psi-mi:“MI:0914”(association)	0.350
CST4	MUC5AC	psi-mi:“MI:0915”(physical association)	0.000
IGHA2	MUC5AC	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0A292G9J6, A1A5Y0, A2VCU8, A6QR11, F7A4A7, O00187, O55225, O57472, O95450, P04275, P57110, P59511, P79331, P80012, P98088, P98089, Q02817, Q13219, Q28295, Q28833, Q2VWQ2, Q3ZCN5, Q4VC17, Q5R3Z7, Q60519, Q61220, Q62635, Q62918, Q62919, Q6PZE0, Q6W4X9, Q6ZRI0, Q7ZXL5, Q80T03, Q80Z19, Q86XX4, Q8CIZ8, Q8CJ69, Q8N8U9, Q8R4K8

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	25
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

36537 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:1179229:G:C	W1155C	1.000
11:1179229:G:T	W1155C	1.000
11:1187829:G:C	W3228C	1.000
11:1187829:G:T	W3228C	1.000
11:1187838:G:C	W3231C	1.000
11:1187838:G:T	W3231C	1.000
11:1188732:G:C	W3529C	1.000
11:1188732:G:T	W3529C	1.000
11:1190022:G:C	W3959C	1.000
11:1190022:G:T	W3959C	1.000
11:1190031:G:C	W3962C	1.000
11:1190031:G:T	W3962C	1.000
11:1178664:T:G	F1103C	0.999
11:1179227:T:A	W1155R	0.999
11:1179227:T:C	W1155R	0.999
11:1182906:G:C	W1587C	0.999
11:1182906:G:T	W1587C	0.999
11:1184016:G:C	W1957C	0.999
11:1184016:G:T	W1957C	0.999
11:1184025:G:C	W1960C	0.999
11:1184025:G:T	W1960C	0.999
11:1184134:T:A	C1997S	0.999
11:1184135:G:C	C1997S	0.999
11:1184215:T:A	C2024S	0.999
11:1184216:G:C	C2024S	0.999
11:1188037:T:A	C3298S	0.999
11:1188038:G:C	C3298S	0.999
11:1188073:T:A	C3310S	0.999
11:1188074:G:C	C3310S	0.999
11:1188092:G:C	R3316P	0.999

dbSNP variants (sampled 300 via entrez): RS1000074471 (11:1157175 A>G), RS1000126349 (11:1156792 C>G,T), RS1000186805 (11:1178909 C>A,T), RS1000197991 (11:1178684 G>A,C), RS1000458146 (11:1199012 C>T), RS1000525807 (11:1179834 A>G), RS1000538694 (11:1179475 C>A,T), RS1000564741 (11:1156845 T>C), RS1000616208 (11:1161816 TG>T,TGG), RS1000687262 (11:1193396 C>T), RS1000753124 (11:1188176 C>G,T), RS1000799397 (11:1168078 C>T), RS1000869171 (11:1195740 A>C,T), RS1001041391 (11:1157233 G>A,C), RS1001053130 (11:1200060 C>T)

Disease associations

OMIM: gene MIM:158373 | disease phenotypes: MIM:148300

GenCC curated gene-disease

Mondo (3): lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096), keratoconus (MONDO:0015486)

Orphanet (3): NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268), OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000563	Keratoconus

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001974_1	Idiopathic pulmonary fibrosis	2.000000e-50
GCST006911_18	Asthma (moderate or severe)	2.000000e-08
GCST007993_21	Asthma (adult onset)	1.000000e-08
GCST009798_52	Asthma	2.000000e-10
GCST90014325_18	Asthma	4.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0000768	idiopathic pulmonary fibrosis
EFO:1002011	adult onset asthma

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D007640	Keratoconus	C11.204.627

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713020 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases reaction, increases expression, increases reaction, increases secretion, affects expression (+2 more)	10
Particulate Matter	decreases reaction, increases abundance, increases expression, affects cotreatment, affects reaction (+2 more)	10
Lipopolysaccharides	decreases reaction, increases expression, increases secretion, increases reaction, affects reaction (+1 more)	7
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, increases secretion	6
pyrazolanthrone	increases reaction, decreases reaction, increases secretion, increases expression, increases abundance	6
Acetylcysteine	decreases reaction, increases expression	5
1,3-dimethylthiourea	decreases reaction, increases expression	4
SB 203580	decreases reaction, increases secretion, increases expression	4
RTKI cpd	decreases reaction, increases expression, increases abundance	4
Acrolein	decreases reaction, increases expression, affects secretion, increases reaction, affects reaction	4
Smoke	decreases reaction, increases abundance, increases expression, increases reaction, affects reaction (+2 more)	4
Resveratrol	decreases reaction, increases expression, decreases expression	3
Air Pollutants	increases abundance, increases expression	3
Vehicle Emissions	increases expression	3
Benzo(a)pyrene	decreases reaction, increases expression, increases reaction, affects reaction	3
Tretinoin	affects cotreatment, increases expression, decreases expression, decreases reaction	3
kaempferol	decreases reaction, increases expression	2
sodium arsenite	decreases expression, decreases secretion, increases expression, decreases reaction	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	2
Histamine	decreases reaction, increases expression, increases secretion	2
Hydrogen Peroxide	decreases reaction, increases expression	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression	2
Tetradecanoylphorbol Acetate	increases reaction, increases secretion, decreases reaction, increases expression	2
Zearalenone	affects cotreatment, decreases expression, increases secretion, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Reactive Oxygen Species	affects reaction, increases expression, increases reaction	2
Cadmium Chloride	affects secretion, decreases expression, increases expression	2
deapi-platycodin D	decreases reaction, increases expression, increases reaction, increases secretion	1
4-oxoretinoic acid	increases expression	1
allyl isothiocyanate	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6AP	HyCyte A-549 KO-hMUC5AC	Cancer cell line	Male
CVCL_E0II	Ubigene HeLa MUC5AC KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118144	PHASE2	COMPLETED	Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
NCT00126581	PHASE2	COMPLETED	Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer
NCT00334815	PHASE2	ACTIVE_NOT_RECRUITING	Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT00368992	PHASE2	COMPLETED	S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
NCT00511485	PHASE2	COMPLETED	Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03)
NCT00950365	PHASE2	COMPLETED	Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer
NCT00955305	PHASE2	TERMINATED	Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
NCT01218516	PHASE2	COMPLETED	A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung
NCT01294306	PHASE2	COMPLETED	MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy
NCT01557959	PHASE2	COMPLETED	Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
NCT01561456	PHASE2	COMPLETED	Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung
NCT01578551	PHASE2	TERMINATED	Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma.
NCT01578668	PHASE2	COMPLETED	Erlotinib Plus Pemetrexed to Treat Lung Adenocarcinoma With Brain Metastases
NCT01819428	PHASE2	TERMINATED	NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma
NCT01935336	PHASE2	COMPLETED	Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
NCT02134912	PHASE2	TERMINATED	S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib
NCT02186847	PHASE2	COMPLETED	Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer