MUC5B

Summary

MUC5B (mucin 5B, oligomeric mucus/gel-forming, HGNC:7516) is a protein-coding gene on chromosome 11p15.5, encoding Mucin-5B (Q9HC84). Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus.

This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases.

Source: NCBI Gene 727897 — RefSeq curated summary.

At a glance

• Gene–disease (curated): interstitial lung disease (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 1,953 total — 1 likely-pathogenic
• Phenotypes (HPO): 27
• MANE Select transcript: NM_002458

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7516
Approved symbol	MUC5B
Name	mucin 5B, oligomeric mucus/gel-forming
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	MG1, MUC-5B
Ensembl gene	ENSG00000117983
Ensembl biotype	protein_coding
OMIM	600770
Entrez	727897

Gene structure

Transcript identifiers

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

ENST00000525715, ENST00000526859, ENST00000527802, ENST00000529681, ENST00000531082

RefSeq mRNA: 1 — MANE Select: NM_002458 NM_002458

CCDS: CCDS44515

Canonical transcript exons

ENST00000529681 — 49 exons

Exon	Start	End
ENSE00000794763	1238871	1239027
ENSE00000794765	1239438	1239566
ENSE00000794769	1239799	1239943
ENSE00000794771	1240045	1240088
ENSE00000988365	1240178	1240375
ENSE00001269768	1252343	1252524
ENSE00001399406	1254694	1254880
ENSE00001400408	1255041	1255266
ENSE00001402975	1254092	1254351
ENSE00001406193	1256156	1256225
ENSE00001410022	1259756	1259842
ENSE00001410855	1260626	1260728
ENSE00001412444	1260351	1260393
ENSE00001414317	1252809	1252980
ENSE00001417638	1257530	1257710
ENSE00001418705	1258099	1258203
ENSE00001419773	1258942	1259061
ENSE00001421228	1258330	1258367
ENSE00001425822	1255383	1255558
ENSE00001428551	1257240	1257271
ENSE00001429640	1256671	1256771
ENSE00001611083	1240851	1251743
ENSE00002143971	1261389	1262172
ENSE00003461629	1234205	1234305
ENSE00003479766	1230005	1230143
ENSE00003487579	1223066	1223193
ENSE00003489258	1230490	1230600
ENSE00003497478	1225681	1225737
ENSE00003515525	1233793	1233848
ENSE00003517862	1226205	1226276
ENSE00003544294	1235303	1235413
ENSE00003548242	1233013	1233268
ENSE00003558947	1236925	1237164
ENSE00003568046	1231423	1231560
ENSE00003577360	1232450	1232544
ENSE00003581756	1229170	1229295
ENSE00003585453	1231996	1232160
ENSE00003591115	1226615	1226876
ENSE00003600451	1229690	1229807
ENSE00003607032	1236386	1236562
ENSE00003617222	1227308	1227398
ENSE00003617605	1227031	1227145
ENSE00003634421	1227675	1227781
ENSE00003651317	1232644	1232770
ENSE00003664093	1235085	1235223
ENSE00003664687	1230936	1231005
ENSE00003669271	1228564	1228765
ENSE00003693145	1234529	1234680
ENSE00003693916	1259963	1260085

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 7.0400 / max 2879.3223, expressed in 167 samples.

FANTOM5 promoters (29 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112383	5.9357	156
112429	0.1697	73
112430	0.1071	41
112419	0.0867	17
206137	0.0730	30
112431	0.0638	22
112432	0.0616	23
206136	0.0568	15
112434	0.0414	18
112423	0.0375	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trachea	UBERON:0003126	99.82	gold quality
gall bladder	UBERON:0002110	99.10	gold quality
mucosa of transverse colon	UBERON:0004991	98.27	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.81	gold quality
bronchus	UBERON:0002185	95.83	gold quality
epithelium of bronchus	UBERON:0002031	95.69	gold quality
bronchial epithelial cell	CL:0002328	94.95	gold quality
tendon of biceps brachii	UBERON:0008188	94.54	gold quality
minor salivary gland	UBERON:0001830	94.36	gold quality
saliva-secreting gland	UBERON:0001044	90.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.23	gold quality
colonic mucosa	UBERON:0000317	89.67	gold quality
endometrium epithelium	UBERON:0004811	89.32	gold quality
mouth mucosa	UBERON:0003729	88.90	gold quality
transverse colon	UBERON:0001157	87.86	gold quality
nasal cavity mucosa	UBERON:0001826	87.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.31	gold quality
rectum	UBERON:0001052	85.93	gold quality
pharyngeal mucosa	UBERON:0000355	83.93	gold quality
pancreatic ductal cell	CL:0002079	83.81	silver quality
colonic epithelium	UBERON:0000397	82.32	gold quality
endocervix	UBERON:0000458	79.99	gold quality
triceps brachii	UBERON:0001509	79.59	gold quality
oral cavity	UBERON:0000167	79.36	gold quality
gluteal muscle	UBERON:0002000	79.31	gold quality
buccal mucosa cell	CL:0002336	78.84	silver quality
urethra	UBERON:0000057	76.98	gold quality
frontal pole	UBERON:0002795	75.74	gold quality
sural nerve	UBERON:0015488	75.03	gold quality
paraflocculus	UBERON:0005351	74.84	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	4710.48
E-MTAB-10287	yes	1343.87
E-GEOD-125970	yes	42.57
E-MTAB-8410	yes	23.27
E-HCAD-1	yes	10.70
E-MTAB-10283	no	1322.19
E-GEOD-99795	no	7.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOSL2, FOXA2, GATA4, GATA5, GATA6, JUND, MYC, NFKB1, NFKB, NFKBID, NKX2-1, RARA, RELA, SP1, SP3, STAT3, TTF1

miRNA regulators (miRDB)

18 targeting MUC5B, 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-548AW	99.99	72.57	3559
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-6823-5P	96.26	65.69	919

Literature-anchored findings (GeneRIF, showing 40)

• analysis of repertoire of unique oligosaccharides (PMID:11825880)
• saliva has additional structure and organization not present in the purified MUC5B mucin (PMID:11853536)
• Structure and biosynthesis of human salivary mucins. (PMID:11996097)
• Level of MG1 is lower in saliva of subjects with dental disease (PMID:12459324)
• results suggest that oligomeric mucin 5, subtype B(MUC5B) in saliva is assembled into much larger linear or branched assemblies through calcium-mediated protein cross-links (PMID:12756239)
• 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)
• expression was observed in 22.0% of the gastric carcinomas and was associated with the “unclassified” histological type and with the absence of venous invasion; expression had no impact on survival and was associated with the co-expression of MUC5AC (PMID:14758553)
• 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)
• 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)
• Possible involvement of MUC5B gene in diffuse panbronchiolitis is demonstrated. (PMID:15709052)
• MUC1, MUC5B and MUC8, but not MUC2 or MUC5AC, are up-regulated in endometrial adenocarcinomas (PMID:16188033)
• Up-regulation of MUC5B in the ear may play an important role in the pathogenesis of middle ear effusions. (PMID:16540890)
• MUC5B mucin gene product secretion is significantly increased in chronic sinusitis compared with control subjects. (PMID:17063754)
• this study demonstrates the important role for methylation and/or histone modifications in regulating the 11p15 mucin genes in epithelial cancer cells. (PMID:17471237)
• Thus gene is up-regulated in sinus mucosa of chronic rhinosinusitis and nasal polyposis. (PMID:17621824)
• both the MUC1-N and MUC1-C subunits evolved from secreted gel-forming mucins and that the MUC1-CD oncogenic function emerged by diversification after evolution from MUC5B (PMID:17671696)
• E2, a sex hormone, stimulates MUC5B gene overexpression by interaction with estrogen receptor alpha (ERalpha) and by acting through extracellular signal-regulated kinase 1/2 (ERK1/2)-mitogen-activated protein kinase (MAPK). (PMID:18688042)
• Results show that oxidative stress induces MUC5B up-regulation, which requires CD44 as well as EGFR and MAPK activation. (PMID:18757307)
• MUC5B (mucin 5B) is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease (PMID:18776153)
• Reflux laryngitis is associated with down-regulation of mucin gene expression. (PMID:18834073)
• The solution MUC5B and gelMUC5B preparations exhibited different biological activity when assayed with freshly plaque bacteria in suspension and in a biofilm. (PMID:19118346)
• A statistically significant association between the long rare MUC5B-MS6 alleles and the occurrence of bladder cancer was identified in the younger group (<60; odds ratio, 4.54; 95% confidence interval, 1.0-20.7; p=0.03). (PMID:19191526)
• NRG1beta1 is a novel mediator of MUC5AC and MUC5B expression in HBECs, and may represent a novel therapeutic target for mucus hypersecretion in respiratory diseases. (PMID:19556605)
• a high concentration of IL-8 is required to increase MUC5B mRNA levels in primary normal differentiated human bronchial epithelial cells (PMID:19596978)
• This study compared polymorphisms in MUC2, MUC5AC, and MUC5B genes in otitis media (OM) patients and controls. (PMID:19718741)
• The structure of the MUC5B in its unpacking state was studied. (PMID:19783639)
• In human nasal polyp epithelial cells, leptin increased the expression of MUC5AC and MUC5B, in a dose- and time-dependent manner, at the gene and protein levels. (PMID:20422702)
• Leptin up-regulates MUC5B expression in human airway epithelial cells via activation of ERK1/2 or p38 MAPK. (PMID:20497020)
• IL-1 beta increased MUC2/MUC5B mRNA levels in human nasal epithelial cells. (PMID:20873538)
• MUC5B and MUC7 from HIV patients, unlike the MUC5B and MUC7 from HIV negative individuals, did not inhibit HIV-1 activity. (PMID:20946627)
• MCP-1 has a novel function in airway epithelium, increasing the two major airway mucins MUC5AC and MUC5B, an effect mediated, at least in part, by a cascade of events initiated by interaction of its receptor CCR2B with G(q) subunits in caveolae (PMID:21097527)
• the ultrastructural distribution of the MUC5B mucin in human palatal and buccal glands (PMID:21194732)
• AQP5 expression increases MUC5AC and MUC5B mucin production (PMID:21455588)
• we identified a common variant in the putative promoter of the gene encoding mucin 5B (MUC5B) that is associated with the development of both familial interstitial pneumonia and sporadic idiopathic pulmonary fibrosis. (PMID:21506741)
• We confirm a recent association with rs35705950 in the putative promoter of MUC5B and sporadic idiopathic pulmonary fibrosis. (PMID:21506748)
• Polymorphisms in MUC1, MUC2, MUC5B and MUC6 genes are not associated with the risk of chronic atrophic gastritis. (PMID:21596555)
• Diallyl disulfide induced MUC5B expression and activated phosphorylation of ERK1/2 MAPK in airway epithelial cells. (PMID:21618303)
• results of this study show that AMPK induces MUC5B expression through the p38 MAPK signaling pathway in airway epithelial cells. (PMID:21619869)
• PGD(2) can induce MUC5B overproduction via ERK MAPK/RSK1/CREB signaling and that DP1 receptor may have suppressive effects in controlling MUC5B overproduction in the airway. (PMID:21832046)
• Agonists of TRPV1 and TRPA1 induced MUC5B release in the human nasal airways in vivo. (PMID:21981454)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	muc5.2	ENSDARG00000058556
danio_rerio	muc5.1	ENSDARG00000070331
danio_rerio	muc5.3	ENSDARG00000099470
mus_musculus	Muc5b	ENSMUSG00000066108
rattus_norvegicus	Muc5b	ENSRNOG00000019846

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), CHRDL1 (ENSG00000101938), TECTA (ENSG00000109927), VWF (ENSG00000110799), KCP (ENSG00000135253), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), OTOGL (ENSG00000165899), VWCE (ENSG00000167992), VWC2L (ENSG00000174453), MUC6 (ENSG00000184956), OTOG (ENSG00000188162), VWC2 (ENSG00000188730), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

Mucin-5B — Q9HC84 (reviewed: Q9HC84)

Alternative names: Cervical mucin, High molecular weight salivary mucin MG1, Mucin-5 subtype B, tracheobronchial, Sublingual gland mucin

All UniProt accessions (2): Q9HC84, H0YDX8

UniProt curated annotations — full annotation on UniProt →

Function. Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical 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 from different CTCK-linked dimers to produce long, disulfide-linked polymers that remain highly compact until secretion.

Subcellular location. Secreted.

Tissue specificity. Expressed on surface airway epithelia. Expressed mainly in mucous cells of submucosal glands of airway tissues. Highly expressed in the sublingual gland. Also found in submaxillary glands, endocervix, gall bladder, and pancreas.

Post-translational modifications. Highly glycosylated. C-, N- and O-glycosylated. C-mannosylated in the Cys-rich subdomains probably on the first Trp residue of the WXXW motif. Highly O-glycosylated in the Ser/Thr-rich tandem repeat (TR) region. The repeat region is about 59% O-glycosylated with a high abundance of NeuAc(2)Hex(1)HexNac1-ol.

Disease relevance. Interstitial lung disease 2 (ILD2) [MIM:178500] A form of interstitial lung disease, a heterogeneous group of diseases affecting the distal part of the lung and characterized by a progressive remodeling of the alveolar interstitium. The disease spectrum ranges from idiopathic interstitial pneumonia or pneumonitis to idiopathic pulmonary fibrosis, that is associated with an increased risk of developing lung cancer. Clinical features of interstitial lung disease include dyspnea, clubbing of the fingers, and restrictive lung capacity. ILD2 inheritance is autosomal dominant. Disease susceptibility is associated with variants affecting the gene represented in this entry. A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis, suggesting that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis.

Domain organisation. The CTCK domain mediates interchain disulfide bonds with another molecule of MUC5B. The cysteine residues in the Cys-rich subdomain repeats are not involved in disulfide bonding.

Induction. Regulated by all-trans-retinoic acid (ATRA) in a cell-type specific manner.

RefSeq proteins (1): NP_002449* (*=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 (391 total): sequence conflict 97, strand 90, glycosylation site 38, helix 33, region of interest 28, compositionally biased region 26, sequence variant 23, disulfide bond 17, turn 12, domain 11, repeat 10, binding site 3, signal peptide 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8OER	ELECTRON MICROSCOPY	3
8OES	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

No AlphaFold model available for Q9HC84 — 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.

Ligand- & substrate-binding residues (3): 194; 311; 358

Disulfide bonds (17): 77–207, 99–244, 425–562, 447–597, 469–477, 895–1026, 917–1061, 926–1023, 944–951, 5075–5221, 5097–5260, 5121–5132, 5653–5705, 5672–5719, 5681–5735, 5685–5737, 0–5741

Glycosylation sites (38): 4134, 4804, 4960, 5017, 5024, 5046, 5096, 5111, 5215, 5486, 5526, 5565, 5566, 5602, 5612, 5663, 5677, 5721, 145, 201 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
1790	poorly secreted.

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: 148 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_REGULATION_OF_BIOLOGICAL_PROCESS_INVOLVED_IN_SYMBIOTIC_INTERACTION, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_CELL_AGGREGATION, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTRASPECIES_INTERACTION_BETWEEN_ORGANISMS, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_HOST, MODULE_88, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, MODULE_6, DANG_BOUND_BY_MYC, MODULE_55, GOCC_GOLGI_LUMEN, WILCOX_RESPONSE_TO_PROGESTERONE_UP, RICKMAN_HEAD_AND_NECK_CANCER_D

GO Biological Process (1): negative regulation of single-species biofilm formation in or on host organism (GO:1900229)

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

GO Cellular Component (6): obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), 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
single-species biofilm formation in or on host organism	1
negative regulation of single-species biofilm formation	1
regulation of single-species biofilm formation in or on host organism	1
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
cellular anatomical structure	1

Protein interactions and networks

STRING

2564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MUC5B	MUC5AC	P98088	962
MUC5B	MUC7	Q8TAX7	942
MUC5B	STATH	P02808	935
MUC5B	MUC1	P13931	933
MUC5B	DMBT1	Q9UGM3	891
MUC5B	MUC12	Q9UKN1	860
MUC5B	HTN1	P15515	851
MUC5B	CST4	P01036	842
MUC5B	MUC17	Q685J3	833
MUC5B	MUC20	Q8N307	833
MUC5B	MUC13	Q9H3R2	833
MUC5B	MUC3A	Q02505	809
MUC5B	MUC2	Q02817	772
MUC5B	LTF	P02788	770
MUC5B	MUC19	Q7Z5P9	723

IntAct

45 interactions, top by confidence:

A	B	Type	Score
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
SNW1	AQR	psi-mi:“MI:0914”(association)	0.650
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
ICE2	HP	psi-mi:“MI:0914”(association)	0.530
KIR2DS2	RHOBTB3	psi-mi:“MI:0914”(association)	0.530
PCK2	IGHA1	psi-mi:“MI:0914”(association)	0.530
ATP6V0A4	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
EGFL8	MPO	psi-mi:“MI:0914”(association)	0.530
C7orf25	MUC5B	psi-mi:“MI:0915”(physical association)	0.400
TIMM50	ZNF724	psi-mi:“MI:0914”(association)	0.350
KIR2DS2	LTN1	psi-mi:“MI:0914”(association)	0.350
PCK2	PIGR	psi-mi:“MI:0914”(association)	0.350
ARHGAP12	IGHA1	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
PIK3CA	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
OR13C3	POTEF	psi-mi:“MI:0914”(association)	0.350
STK11	A2ML1	psi-mi:“MI:0914”(association)	0.350
USB1	IGLL5	psi-mi:“MI:0914”(association)	0.350
EBF2	LILRA5	psi-mi:“MI:0914”(association)	0.350
JAK2	BACH1	psi-mi:“MI:0914”(association)	0.350
NOX4	HP	psi-mi:“MI:0914”(association)	0.350
NTNG1	AMY1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Affinity Capture-MS), MUC5B (Proximity Label-MS), MUC5B (Affinity Capture-MS)

ESM2 similar proteins: C9J798, O18735, O43374, O60568, O70293, O70309, O75051, O95294, O97583, P00533, P04626, P04629, P06494, P18084, P21860, P26013, P35739, P43250, P52849, P52850, P55245, P70206, P70207, P70424, P80747, P97711, Q01279, Q0VBD0, Q3UFB7, Q4V7F2, Q5EA46, Q5R6K5, Q5RB22, Q60553, Q61526, Q62799, Q6W4X9, Q8IZ69, Q91009, Q91XD7

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

1953 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	1328
Likely benign	343
Benign	190

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3256937	NM_002458.3(MUC5B):c.897_898del (p.Ala300fs)	Likely pathogenic

SpliceAI

7544 predictions. Top by Δscore:

Variant	Effect	Δscore
11:1223192:AGGT:A	donor_loss	1.0000
11:1223193:GGT:G	donor_loss	1.0000
11:1223194:GTAA:G	donor_loss	1.0000
11:1223195:T:G	donor_loss	1.0000
11:1225600:G:T	donor_gain	1.0000
11:1225679:A:AG	acceptor_gain	1.0000
11:1225680:G:GG	acceptor_gain	1.0000
11:1225680:GA:G	acceptor_gain	1.0000
11:1225734:GGCG:G	donor_gain	1.0000
11:1225735:GCG:G	donor_gain	1.0000
11:1225735:GCGG:G	donor_gain	1.0000
11:1225738:G:GG	donor_gain	1.0000
11:1225738:GT:G	donor_loss	1.0000
11:1225739:T:G	donor_loss	1.0000
11:1226274:GCC:G	donor_gain	1.0000
11:1226277:G:GG	donor_gain	1.0000
11:1226611:ACAGC:A	acceptor_loss	1.0000
11:1226612:CAG:C	acceptor_loss	1.0000
11:1226613:A:AG	acceptor_gain	1.0000
11:1226613:AG:A	acceptor_loss	1.0000
11:1226614:G:GG	acceptor_gain	1.0000
11:1226614:G:GT	acceptor_loss	1.0000
11:1226614:GCCC:G	acceptor_gain	1.0000
11:1226614:GCCCT:G	acceptor_gain	1.0000
11:1226703:T:TA	acceptor_gain	1.0000
11:1226874:GCG:G	donor_gain	1.0000
11:1226875:CGGT:C	donor_loss	1.0000
11:1226877:G:GG	donor_gain	1.0000
11:1227063:T:TA	acceptor_gain	1.0000
11:1227146:G:C	donor_loss	1.0000

AlphaMissense

36858 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:1239008:G:C	W1145C	1.000
11:1239008:G:T	W1145C	1.000
11:1242250:G:C	W1790C	1.000
11:1242250:G:T	W1790C	1.000
11:1242259:G:C	W1793C	1.000
11:1242259:G:T	W1793C	1.000
11:1249291:G:C	W4137C	1.000
11:1249291:G:T	W4137C	1.000
11:1257544:G:C	W5428C	1.000
11:1257544:G:T	W5428C	1.000
11:1239006:T:A	W1145R	0.999
11:1239006:T:C	W1145R	0.999
11:1239481:G:C	W1166C	0.999
11:1239481:G:T	W1166C	0.999
11:1241407:G:C	W1509C	0.999
11:1241407:G:T	W1509C	0.999
11:1242257:T:A	W1793R	0.999
11:1242257:T:C	W1793R	0.999
11:1242368:T:A	C1830S	0.999
11:1242368:T:C	C1830R	0.999
11:1242369:G:C	C1830S	0.999
11:1242449:T:A	C1857S	0.999
11:1242450:G:A	C1857Y	0.999
11:1242450:G:C	C1857S	0.999
11:1242504:G:C	R1875P	0.999
11:1243849:G:C	W2323C	0.999
11:1243849:G:T	W2323C	0.999
11:1243958:T:A	C2360S	0.999
11:1243959:G:C	C2360S	0.999
11:1244039:T:A	C2387S	0.999

dbSNP variants (sampled 300 via entrez): RS1000075551 (11:1226175 G>A), RS1000104887 (11:1257033 C>A), RS1000160299 (11:1253815 T>A), RS1000174488 (11:1235195 A>G), RS1000327099 (11:1225784 G>A), RS1000444500 (11:1258453 G>A), RS1000473088 (11:1234007 C>G), RS1000652210 (11:1223006 T>C), RS1000700554 (11:1222317 G>A,C), RS1000751230 (11:1222531 G>A), RS1000762685 (11:1249111 G>C), RS1000863338 (11:1227481 C>A,T), RS1000865973 (11:1238406 C>T), RS1000880149 (11:1258551 C>A), RS1000892206 (11:1238647 G>A)

Disease associations

OMIM: gene MIM:600770 | disease phenotypes: MIM:178500

GenCC curated gene-disease

Disease	Classification	Inheritance
interstitial lung disease	Limited	Autosomal recessive
interstitial lung disease 2	Limited	Autosomal dominant

Mondo (4): interstitial lung disease 2 (MONDO:0800497), antisynthetase syndrome (MONDO:0019344), pulmonary fibrosis (MONDO:0002771), interstitial lung disease (MONDO:0015925)

Orphanet (3): Idiopathic pulmonary fibrosis (Orphanet:2032), Acute interstitial pneumonia (Orphanet:79126), Antisynthetase syndrome (Orphanet:81)

HPO phenotypes

27 total (27 of 27 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001063	Acrocyanosis
HP:0001394	Cirrhosis
HP:0002020	Gastroesophageal reflux
HP:0002092	Pulmonary arterial hypertension
HP:0002094	Dyspnea
HP:0002110	Bronchiectasis
HP:0002206	Pulmonary fibrosis
HP:0002875	Exertional dyspnea
HP:0003546	Exercise intolerance
HP:0006519	Alveolar cell carcinoma
HP:0006530	Abnormal pulmonary interstitial morphology
HP:0010444	Pulmonic regurgitation
HP:0010702	Increased circulating immunoglobulin concentration
HP:0012378	Fatigue
HP:0012735	Cough
HP:0025175	Honeycomb lung
HP:0025179	Ground-glass opacification
HP:0025390	Reticular pattern on pulmonary HRCT
HP:0030830	Crackles
HP:0031631	Subpleural honeycombing
HP:0031950	Usual interstitial pneumonia
HP:0032341	Reduced forced vital capacity
HP:0032977	Elevated bronchoalveolar lavage fluid neutrophil proportion
HP:0033367	Orthodeoxia
HP:0045051	Decreased DLCO
HP:0100759	Clubbing of fingers

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001974_1	Idiopathic pulmonary fibrosis	2.000000e-50
GCST001974_4	Idiopathic pulmonary fibrosis	1.000000e-12
GCST001974_5	Idiopathic pulmonary fibrosis	3.000000e-11
GCST004986_5	Idiopathic pulmonary fibrosis	1.000000e-66
GCST005547_4	Major depressive disorder	2.000000e-09
GCST007666_8	Depressive symptom improvement	1.000000e-06
GCST007798_126	Asthma	4.000000e-12
GCST007799_29	Asthma (adult onset)	3.000000e-12
GCST009501_4	Interstitial lung abnormalities	3.000000e-27
GCST009501_5	Interstitial lung abnormalities	4.000000e-27
GCST009502_1	Subpleural-predominant interstitial lung abnormalities	5.000000e-29
GCST009502_6	Subpleural-predominant interstitial lung abnormalities	2.000000e-29
GCST009758_17	Idiopathic pulmonary fibrosis	1.000000e-203
GCST009798_52	Asthma	2.000000e-10
GCST010206_5	Anorectal malformation	8.000000e-17

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0000768	idiopathic pulmonary fibrosis
EFO:0007006	depressive symptom measurement
EFO:1002011	adult onset asthma

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D017563	Lung Diseases, Interstitial	C08.381.483
D011658	Pulmonary Fibrosis	C08.381.483.652; C23.550.355.644
C537778	Antisynthetase syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs35705950	MUC5B		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, decreases secretion, increases expression, increases secretion	6
Air Pollutants	increases abundance, increases expression, increases response to substance	3
Benzo(a)pyrene	affects methylation, decreases methylation	2
Smoke	increases abundance, increases expression	2
Zearalenone	increases expression, increases secretion, affects cotreatment, decreases expression, decreases secretion	2
Cadmium Chloride	affects secretion, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
deoxynivalenol	increases expression, increases secretion	1
potassium persulfate	increases expression	1
decabromobiphenyl ether	decreases reaction, increases expression	1
sodium arsenite	decreases expression, decreases secretion, decreases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
ochratoxin A	decreases expression, decreases secretion, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
mustard oil	increases secretion	1
aflatoxin B2	increases methylation	1
nivalenol	increases expression, increases secretion	1
fumonisin B1	increases expression, increases secretion	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6AQ	HyCyte A-549 KO-hMUC5B	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00637065	PHASE4	UNKNOWN	Bosentan in Pulmonary Hypertension in Interstitial Lung Disease Treatment Study
NCT00882817	PHASE4	COMPLETED	Pulmonary Rehabilitation in Interstitial Lung Diseases
NCT02143687	PHASE4	COMPLETED	Patients With Pulmonary Hypertension or Interstitial Lung Disease at Altitude - Effect of Oxygen on Exercise Performance
NCT02150616	PHASE4	UNKNOWN	Patients With Pulmonary Hypertension or Interstitial Lung Disease at Altitude - Effect of Oxygen on Breathing and Sleep
NCT02622022	PHASE4	COMPLETED	Palliation of Dyspnea With Morphine in Patients With Interstitial Lung Disease
NCT02821689	PHASE4	UNKNOWN	Pirfenidone in Progressive Interstitial Lung Disease Associated With Clinically Amyopathic Dermatomyositis
NCT04036721	PHASE4	SUSPENDED	Coorticosteroid Regimen in Patients With Anti-PD-1/PD-L1 Induced Pneumonitis
NCT04311567	PHASE4	TERMINATED	Effects of Tofacitinib vs Methotrexate on Rheumatoid Arthritis Interstitial Lung Disease
NCT04619680	PHASE4	COMPLETED	The Study of the Use of Nintedanib in Slowing Lung Disease in Patients With Fibrotic or Non-Fibrotic Interstitial Lung Disease Related to COVID-19
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT04988282	PHASE4	COMPLETED	Systemic Corticosteroids in Treatment of Post-COVID-19 Interstitial Lung Disease
NCT05129410	PHASE4	UNKNOWN	Clinical Study of MMF in Treatment of IIM-ILD and Its Effect on Peripheral Blood Treg Cells
NCT05375435	PHASE4	UNKNOWN	Efficacy and Safety of Triple Therapy in Patients With Anti-MDA5 Antibody-positive Dermatomyositis
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT07077486	PHASE4	RECRUITING	Effects of Telitacicept vs Cyclophosphamide on Lupus Related Interstitial Lung Disease
NCT07319598	PHASE4	RECRUITING	A Study to Test Tetrandrine Tablets for Connective Tissue Disease-Related Lung Disease
NCT07570888	PHASE4	NOT_YET_RECRUITING	This is a Trial Designed to Evaluate the Combination of Nerandomilast With Mycophenolate Across a Wide Variety of Pulmonary Fibrosis Subtypes, With the Aim of Providing Clinicians With Assurance That This is an Appropriate Therapeutic Combination.
NCT01570764	PHASE3	COMPLETED	Cyclophosphamide Systemic Sclerosis Associated Interstitial Lung Disease
NCT02896205	PHASE3	COMPLETED	Study to Compare the Efficacy of Mycophenolate Mofetil in Systemic Sclerosis Related Early Interstitial Lung Disease
NCT03018756	PHASE3	COMPLETED	Nebulized Fentanyl in Patients With Mild to Moderate Interstitial Lung Disease and Chronic Dyspnea
NCT03770663	PHASE3	UNKNOWN	Cyclophosphamide and Azathioprine vs Tacrolimus in Antisynthetase Syndrome-related Interstitial Lung Disease
NCT04708782	PHASE3	COMPLETED	Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
NCT04905693	PHASE3	ENROLLING_BY_INVITATION	Extension Study of Inhaled Treprostinil in Subjects With Fibrotic Lung Disease
NCT05255991	PHASE3	COMPLETED	Multinational Study of Efficacy and Safety of Inhaled Treprostinil in Subjects With Idiopathic Pulmonary Fibrosis
NCT05943535	PHASE3	RECRUITING	Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
NCT06297096	PHASE3	RECRUITING	Study of the Efficacy of Nintedanib+Tocilizumab in Patients With Systemic Sclerosis and Interstitial Lung Disease
NCT06806592	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Helps People With Lungfibrosis Related to Rheumatic Diseases
NCT07179380	PHASE3	RECRUITING	Efficacy and Safety Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
NCT07201922	PHASE3	RECRUITING	A Study to Test Whether Nerandomilast Can Help Slow Down Changes in the Lung in People With a Family History of Pulmonary Fibrosis
NCT07234032	PHASE3	NOT_YET_RECRUITING	An Open-Label Extension Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
NCT07540988	PHASE3	NOT_YET_RECRUITING	FIBRONEER-ACT: A Study to Test Whether Nerandomilast Helps People With Fibrosing Interstitial Lung Disease at Risk for Disease Progression
NCT07613099	PHASE3	NOT_YET_RECRUITING	Evaluation of Fibrotic Disease Activity in Cardiopulmonary Disorders Using 18F-Fibroblast Activation Protein Inhibitor (18F-FAPI-74 PET/CT Imaging)
NCT05979441	PHASE3	ENROLLING_BY_INVITATION	A Study to Assess the Long-term Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod in Adults With Active Idiopathic Inflammatory Myopathy
NCT00004563	PHASE3	COMPLETED	Scleroderma Lung Disease
NCT00052039	PHASE3	TERMINATED	A Randomized, Double-Blind, Three-Arm, Phase 3b Study Comparing the Safety and Efficacy of Interferon Gamma-1b With Azathioprine, and Azathioprine Alone in Patients With IPF Receiving Prednisone
NCT00075998	PHASE3	TERMINATED	The INSPIRE Trial: A Study of Interferon Gamma-1b for Idiopathic Pulmonary Fibrosis (IPF)
NCT00076635	PHASE3	TERMINATED	An Open-Label Study of the Safety of Interferon Gamma-1b in Patients With IPF
NCT00517933	PHASE3	COMPLETED	Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis
NCT00639496	PHASE3	COMPLETED	Study of the Effects of High-dose N-acetylcysteine (NAC) in Idiopathic Pulmonary Fibrosis (IPF)