MR1
protein-codingmajor histocompatibility complex, class I-related, the group of C1-set domain containing|Minor histocompatibility antigens
Gene summary
MAIT (mucosal-associated invariant T-cells) lymphocytes represent a small population of T-cells primarily found in the gut. The protein encoded by this gene is an antigen-presenting molecule that presents metabolites of microbial vitamin B to MAITs. This presentation may activate the MAITs to regulate the amounts of specific types of bacteria in the gut. Several transcript variants encoding different isoforms have been found for this gene, and a pseudogene of it has been detected about 36 kbp upstream on the same chromosome. [provided by RefSeq, Jul 2015]
- HLALS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Medical treatment (eg, with benzodiazepines) have been described as beneficial
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001385161.1. 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 | 4 | 1 | 5 | |||
| missense | 55 | 5 | 60 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 55 | 9 | 1 | 65 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001372090.1 | 6 | MANE Select | |
| Ensembl | ENSP00000356552.5 | 6 | MANE Select | |
| RefSeq | NP_001181928.1 | 6 | Standard | |
| RefSeq | NP_001181929.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cytokine production involved in immune response
- antigen processing and presentation of peptide antigen via MHC class I
- immune response
- interleukin-1 beta production
- interleukin-17 production
Molecular Function
- protein binding
- MHC class I receptor activity
Cellular Component
- extracellular region
- extracellular space
- endoplasmic reticulum
- endoplasmic reticulum membrane
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367580
- Coding exons
- 6
- Length
- 28008
- Individuals with no LoFs
- 125642
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 106
- Defined
- 125748
- p
- 0.000422
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.343 | 205 | 192 | 1.07 | 0.0000103 | 2222 |
| Missense (PolyPhen) | 79 | 73.035 | 1.0817 | 918 | ||
| Synonymous | -0.124 | 76 | 74.6 | 1.02 | 0.00000422 | 660 |
| Loss of Function | -1.33 | 23 | 17.1 | 1.35 | 7.98e-7 | 190 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.0023 | 0.0023 | notable |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Antigen-presenting molecule specialized in presenting microbial vitamin B metabolites. Involved in the development and expansion of a small population of T-cells expressing an invariant T-cell receptor alpha chain called mucosal-associated invariant T- cells (MAIT). MAIT lymphocytes are preferentially located in the gut lamina propria and therefore may be involved in monitoring commensal flora or serve as a distress signal. Expression and MAIT cell recognition seem to be ligand-dependent. {ECO:0000269|PubMed:12794138, ECO:0000269|PubMed:19416870}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.818
- RVIS EVS
- 0.49
- RVIS percentile EVS
- 79.38
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.123
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |