MUC4
protein-codingmucin 4, cell surface associated, the group of Mucins
Gene summary
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. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~65.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MUC4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018406.7. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 25 | 165 | 1 | 191 | ||
| missense | 126 | 60 | 2 | 188 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 1 | 5 | |||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 162 | 226 | 3 | 391 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060876.5 | 25 | MANE Select | |
| Ensembl | ENSP00000417498.3 | 25 | MANE Select | |
| RefSeq | NP_004523.3 | 24 | Standard | |
| RefSeq | NP_612154.2 | 23 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Dectin-2 family
- Metabolism of proteins
- C-type lectin receptors (CLRs)
- Innate Immune System
Biological Process
- stimulatory C-type lectin receptor signaling pathway
- cell-matrix adhesion
- regulation of signaling receptor activity
- O-glycan processing
- maintenance of gastrointestinal epithelium
Molecular Function
- ErbB-2 class receptor binding
- extracellular matrix constituent, lubricant activity
Cellular Component
- extracellular space
- Golgi lumen
- plasma membrane
- integral component of plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000463781
- Coding exons
- 25
- Length
- 65513
- Individuals with no LoFs
- 125389
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 359
- Defined
- 125748
- p
- 0.00143
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -18.9 | 5424 | 2.68e+3 | 2.03 | 0.000154 | 31579 |
| Missense (PolyPhen) | 405 | 255.78 | 1.5834 | 2762 | ||
| Synonymous | -20.5 | 2070 | 1.18e+3 | 1.76 | 0.0000839 | 12685 |
| Loss of Function | 1.61 | 93 | 111 | 0.835 | 0.00000563 | 1402 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00049 | 0.00049 | rare |
| Latino/Admixed American | 0.0013 | 0.0013 | notable |
| Ashkenazi Jewish | 0.0030 | 0.0030 | notable |
| East Asian | 0.0027 | 0.0026 | notable |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.0017 | 0.0017 | notable |
| South Asian | 0.00099 | 0.00098 | rare |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a role in tumor progression. Ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation. Has anti-adhesive properties. Seems to alter cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and in its ability to act as an intramembrane ligand for ERBB2. Plays an important role in cell proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. The MUC4-ERBB2 complex causes site-specific phosphorylation of the ERBB2 'Tyr-1248'. 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. {ECO:0000269|PubMed:12102554, ECO:0000269|PubMed:16049287, ECO:0000269|PubMed:16814944, ECO:0000269|PubMed:16914178}.;
Intolerance Scores
- LoFtool
- 0.938
- RVIS EVS
- 6.32
- RVIS percentile EVS
- 99.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |