MSN
protein-codingmoesin, the group of FERM domain containing
Gene summary
Moesin (for membrane-organizing extension spike protein) is a member of the ERM family which includes ezrin and radixin. ERM proteins appear to function as cross-linkers between plasma membranes and actin-based cytoskeletons. Moesin is localized to filopodia and other membranous protrusions that are important for cell-cell recognition and signaling and for cell movement. [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 ~153.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010514
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0010514
Submitter: ClinGen
MSN was first reported in relation to X-linked combined immunodeficiency due to moesin deficiency in 2016 (Lagresle-Peyrou et al., PMID: 27405666). This condition is characterized by T-B-NK- lymphopenia, recurrent infections, decreased circulating antibody level, and sepsis and leg ulcers in some patients. The age of onset and phenotypic presentation varied among patients reported. Four variants (missense & nonsense) that have been reported in 11 unrelated probands in 7 publications (PMIDs: 27405666, 28378256, 29556235, 32506361, 34093558, 36119109, 35754805, 34453634) are included in this curation. The variant was maternally inherited from unaffected mothers in all cases and in one case, the variant occured de novo in the proband's mother. Carrier mothers had skewed X chromosome inactivation in all hematopoietic lineages. Variants segregated with disease in 3 families. While seven probands were hemizygous for the same missense variant, p.Arg171Trp, it is likely that this variant occurs on different haplotypes, indicating that p.Arg171 may be a mutation hotspot. The mechanism of pathogenicity is known to be loss of function. This gene-disease association is also supported by mouse model, expression studies, functional alteration in non-patient cells, biochemical function, and rescue in patient cells (PMIDs: 22875842, 36119109, 34798556, 28978692, 27405666). In summary, MSN is definitively associated with X-linked combined immunodeficiency due to moesin deficiency. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
Inheritance Pattern: XL
Disease ID:MONDO:0010514
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XL
Disease ID:MONDO:0010514
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010514
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious
Intervention: Allergy/Immunology/Infectious
Rationale: Individuals have been described with early onset and recurrent bacterial or varicella zoster virus infections, and awareness may allow preventive measures and early and aggressive treatments of infections
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MSN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002444.3. 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 | 9 | 63 | 8 | 80 | ||
| missense | 1 | 1 | 138 | 14 | 7 | 161 |
| nonsense | 6 | 2 | 10 | 1 | 19 | |
| start loss | 0 | |||||
| frameshift | 5 | 2 | 1 | 8 | ||
| splice donor/acceptor (+/-2bp) | 2 | 18 | 20 | |||
| Total | 12 | 7 | 176 | 78 | 15 | 288 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002435.1 | 13 | MANE Select | |
| Ensembl | ENSP00000353408.5 | 13 | MANE Select | |
| RefSeq | NP_001427707.1 | 13 | Standard | |
| Ensembl | ENSP00000477441.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| msna | Danio rerio | Structure: blood vessel endothelial cell Quality: physical object quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tight junction - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Proteoglycans in cancer - Homo sapiens (human)
- Measles - Homo sapiens (human)
- Leukocyte transendothelial migration - Homo sapiens (human)
Biological Process
- immunological synapse formation
- cytoskeleton organization
- leukocyte cell-cell adhesion
- regulation of cell shape
- regulation of cell size
Molecular Function
- double-stranded RNA binding
- actin binding
- signaling receptor binding
- structural constituent of cytoskeleton
- protein binding
Cellular Component
- uropod
- extracellular space
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360270
- Coding exons
- 13
- Length
- 153535
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.93 | 110 | 237 | 0.464 | 0.0000200 | 3830 |
| Missense (PolyPhen) | 22 | 90.523 | 0.24303 | 1517 | ||
| Synonymous | 0.0771 | 82 | 82.9 | 0.989 | 0.00000619 | 1030 |
| Loss of Function | 4.44 | 0 | 23.0 | 0.00 | 0.00000173 | 386 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probably involved in connections of major cytoskeletal structures to the plasma membrane. May inhibit herpes simplex virus 1 infection at an early stage. Plays a role in regulating the proliferation, migration, and adhesion of human lymphoid cells and participates in immunologic synapse formation (PubMed:27405666). {ECO:0000269|PubMed:21549406, ECO:0000269|PubMed:27405666}.;
- Disease
- DISEASE: Immunodeficiency 50 (IMD50) [MIM:300988]: A primary immunodeficiency disorder characterized by onset of recurrent bacterial or varicella zoster virus infections in early childhood, profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, and a poor immune response to vaccine antigens. {ECO:0000269|PubMed:27405666}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.453
Intolerance Scores
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.973
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |