MICB
protein-codingMHC class I polypeptide-related sequence B, the group of C1-set domain containing
Gene summary
This gene encodes a heavily glycosylated protein which is a ligand for the NKG2D type II receptor. Binding of the ligand activates the cytolytic response of natural killer (NK) cells, CD8 alphabeta T cells, and gammadelta T cells which express the receptor. This protein is stress-induced and is similar to MHC class I molecules; however, it does not associate with beta-2-microglobulin or bind peptides. Alternative splicing 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 ~16.2 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 MICB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005931.5. 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 | 2 | 2 | 4 | |||
| missense | 48 | 5 | 53 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 53 | 5 | 2 | 60 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005922.2 | 6 | MANE Select | |
| Ensembl | ENSP00000252229.6 | 6 | MANE Select | |
| RefSeq | NP_001276089.1 | 5 | Standard | |
| RefSeq | NP_001276090.1 | 6 | 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)
- Immune System
- Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
- Adaptive Immune System
Biological Process
- T cell mediated cytotoxicity
- immune response-activating cell surface receptor signaling pathway
- immune response
- response to oxidative stress
- response to heat
Molecular Function
- natural killer cell lectin-like receptor binding
Cellular Component
- extracellular space
- plasma membrane
- external side of plasma membrane
- cell surface
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000252229
- Coding exons
- 6
- Length
- 16244
- Individuals with no LoFs
- 124743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 124750
- p
- 0.0000281
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.554 | 194 | 217 | 0.894 | 0.0000116 | 2469 |
| Missense (PolyPhen) | 106 | 112.43 | 0.94282 | 1448 | ||
| Synonymous | 0.724 | 79 | 87.6 | 0.902 | 0.00000476 | 772 |
| Loss of Function | 1.36 | 9 | 14.6 | 0.615 | 6.25e-7 | 166 |
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) | 0.000054 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| 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:11491531, ECO:0000269|PubMed:11777960, ECO:0000269|PubMed:9497295}.;
- Disease
- DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269|PubMed:17003176}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. The MICB*004 allele is associated with rheumatoid arthritis.; DISEASE: Note=Genetic variation in MICB is associated with cytomegalovirus and herpes simplex virus I seropositivity and this may be associated with schizophrenia risk.;
Intolerance Scores
- LoFtool
- 0.840
- RVIS EVS
- 1.82
- RVIS percentile EVS
- 96.99
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.178
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |