MAL2
protein-codingmal, T cell differentiation protein 2, the group of MARVEL domain containing
Gene summary
This gene encodes a multispan transmembrane protein belonging to the MAL proteolipid family. The protein is a component of lipid rafts and, in polarized cells, it primarily localizes to endosomal structures beneath the apical membrane. It is required for transcytosis, an intracellular transport pathway used to deliver membrane-bound proteins and exogenous cargos from the basolateral to the apical surface. [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 ~80.6 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 MAL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_052886.3. 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 | 1 | 1 | ||||
| missense | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 14 | 0 | 0 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_443118.1 | 4 | MANE Select | |
| Ensembl | ENSP00000479708.1 | 4 | MANE Select | |
| Ensembl | ENSP00000483044.1 | 3 | Standard | |
| Ensembl | ENSP00000483044.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- myelination
- transcytosis
Molecular Function
- protein binding
- structural constituent of myelin sheath
Cellular Component
- endomembrane system
- integral component of membrane
- apical plasma membrane
- membrane raft
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000276681
- Coding exons
- 5
- Length
- 80641
- Individuals with no LoFs
- 124645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 124651
- p
- 0.0000241
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.496 | 67 | 79.4 | 0.843 | 0.00000411 | 1085 |
| Missense (PolyPhen) | 28 | 42.269 | 0.66243 | 525 | ||
| Synonymous | 0.0890 | 33 | 33.7 | 0.980 | 0.00000205 | 349 |
| Loss of Function | 1.43 | 2 | 5.69 | 0.351 | 2.41e-7 | 77 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Member of the machinery of polarized transport. Required for the indirect transcytotic route at the step of the egress of the transcytosing cargo from perinuclear endosomes in order for it to travel to the apical surface via a raft-dependent pathway. {ECO:0000269|PubMed:12370246}.;
Recessive Scores
- pRec
- 0.133
Essentials
- Indispensability pred.
- E
- Indispensability score
- 0.852
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |