MICA
protein-codingMHC class I polypeptide-related sequence A, the group of C1-set domain containing
Gene summary
This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.5 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 MICA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001177519.3. 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 | 2 | 3 | |||
| missense | 39 | 4 | 1 | 44 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 0 | 0 | 42 | 7 | 1 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001170990.1 | 5 | MANE Select | |
| Ensembl | ENSP00000413079.1 | 5 | MANE Select | |
| RefSeq | NP_001276081.1 | 4 | Standard | |
| RefSeq | NP_001276082.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Natural killer cell mediated cytotoxicity - Homo sapiens (human)
- Allograft Rejection
- Immune System
- Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Biological Process
- T cell mediated cytotoxicity
- immune response to tumor cell
- immune response
- cellular response to DNA damage stimulus
- response to heat
Molecular Function
- protein binding
- beta-2-microglobulin binding
- natural killer cell lectin-like receptor binding
Cellular Component
- extracellular space
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- external side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000449934
- Coding exons
- 5
- Length
- 11737
- Individuals with no LoFs
- 114318
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 114325
- p
- 0.0000306
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.802 | 144 | 174 | 0.829 | 0.00000886 | 2116 |
| Missense (PolyPhen) | 46 | 55.848 | 0.82367 | 773 | ||
| Synonymous | 0.658 | 59 | 65.8 | 0.897 | 0.00000337 | 607 |
| Loss of Function | 1.96 | 6 | 13.9 | 0.432 | 6.42e-7 | 166 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00015 | 0.00015 | rare |
| Latino/Admixed American | 0.00015 | 0.00015 | rare |
| 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: Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T- cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis. {ECO:0000269|PubMed:10426993, ECO:0000269|PubMed:11224526, ECO:0000269|PubMed:11491531, ECO:0000269|PubMed:11777960, ECO:0000269|PubMed:9497295}.;
- Disease
- DISEASE: Note=Anti-MICA antibodies and ligand shedding are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS)to multiple myeloma.; DISEASE: Psoriasis 1 (PSORS1) [MIM:177900]: A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Psoriatic arthritis (PSORAS) [MIM:607507]: An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). {ECO:0000269|PubMed:10323458}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Intolerance Scores
- RVIS EVS
- 3.71
- RVIS percentile EVS
- 99.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.101
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |