MUC16
protein-codingmucin 16, cell surface associated, the group of Mucins
Gene summary
This gene encodes a protein that is a member of the mucin family. Mucins are high molecular weight, O-glycosylated proteins that play an important role in forming a protective mucous barrier, and are found on the apical surfaces of the epithelia. The encoded protein is a membrane-tethered mucin that contains an extracellular domain at its amino terminus, a large tandem repeat domain, and a transmembrane domain with a short cytoplasmic domain. The amino terminus is highly glycosylated, while the repeat region contains 156 amino acid repeats unit that are rich in serines, threonines, and prolines. Interspersed within the repeats are Sea urchin sperm protein Enterokinase and Agrin (SEA) modules, leucine-rich repeats and ankyrin (ANK) repeats. These regions together form the ectodomain, and there is a potential cleavage site found near an SEA module close to the transmembrane domain. This protein is thought to play a role in forming a barrier, protecting epithelial cells from pathogens. Products of this gene have been used as a marker for different cancers, with higher expression levels associated with poorer outcomes. [provided by RefSeq, May 2017]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~161.5 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 MUC16 variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . 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 | 44 | 23 | 67 | |||
| missense | 24 | 30 | 54 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 0 | 68 | 53 | 121 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001388430.1 | 93 | Standard | |
| RefSeq | NP_001401615.1 | 94 | Standard | |
| RefSeq | NP_001401616.1 | 90 | Standard | |
| RefSeq | NP_078966.2 | 84 | 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 adhesion
- O-glycan processing
Molecular Function
- protein binding
Cellular Component
- Golgi lumen
- plasma membrane
- integral component of membrane
- extrinsic component of membrane
- vesicle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000397910
- Coding exons
- 84
- Length
- 132499
- Individuals with no LoFs
- 124430
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 274
- Defined
- 124704
- p
- 0.00110
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -8.06 | 9193 | 7.26e+3 | 1.27 | 0.000357 | 91882 |
| Missense (PolyPhen) | 651 | 575.15 | 1.1319 | 7547 | ||
| Synonymous | -8.41 | 3384 | 2.82e+3 | 1.20 | 0.000145 | 32884 |
| Loss of Function | 5.45 | 232 | 341 | 0.681 | 0.0000157 | 5070 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0050 | 0.0048 | notable |
| Latino/Admixed American | 0.0011 | 0.0010 | notable |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.00062 | 0.00061 | rare |
| Finnish | 0.00032 | 0.00032 | rare |
| European (Non-Finnish) | 0.00085 | 0.00082 | rare |
| South Asian | 0.0011 | 0.0011 | notable |
| Other | 0.0012 | 0.0012 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.998
- RVIS EVS
- 29.75
- RVIS percentile EVS
- 100
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0690
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |