HMHB1
protein-codinghistocompatibility minor HB-1, the group of Minor histocompatibility antigens
Gene summary
This gene encodes one of the minor histocompatibility antigens, which play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). This gene is only expressed in B cell acute lymphoblastic leukemia cells and Epstein-Barr virus-transformed B cells. The translation of this mRNA initiates at a non-AUG (CUG) codon. [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 ~8.6 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 HMHB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021182.3. 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 | 0 | |||||
| missense | 4 | 1 | 5 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 4 | 1 | 0 | 5 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067005.1 | 2 | MANE Select | |
| Ensembl | ENSP00000289448.3 | 2 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- adaptive immune response
- regulation of gene expression
- regulation of cytolysis
- cellular response to tumor necrosis factor
- positive regulation of interferon-gamma secretion
Molecular Function
- molecular_function
Cellular Component
- cellular_component
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000289448
- Coding exons
- 2
- Length
- 8559
- Individuals with no LoFs
- 124741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124743
- p
- 0.00000802
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.468 | 25 | 19.2 | 1.30 | 8.75e-7 | 259 |
| Missense (PolyPhen) | 2 | 1.0696 | 1.8698 | 11 | ||
| Synonymous | -0.653 | 11 | 8.57 | 1.28 | 4.55e-7 | 76 |
| Loss of Function | -2.06 | 2 | 0.473 | 4.22 | 1.99e-8 | 6 |
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 | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Precursor of the histocomplatibility antigen HB-1. More generally, minor histocomplatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA- identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocomplatibility antigen in HLA-matched sibling marrow transplants. HB-1 is presented on the cell surface by MHC class I HLA-B44. This complex specifically elicits donor-cytotoxic T lymphocyte (CTL) reactivity in B-cell acute lymphoblastic leukemia (B-ALL) after treatment by HLA-identical allogenic bone marrow transplantation (BMT). It induces cell recognition and lysis by CTL. However, HB-1 restricted expression in B-ALL cells and not in normal tissues may allow a specific CTL reactivity against B-ALL without the risk of evoking graft-versus-host disease. {ECO:0000269|PubMed:15102363, ECO:0000269|PubMed:8992968, ECO:0000269|PubMed:9892612}.;
Intolerance Scores
- RVIS EVS
- 0.19
- RVIS percentile EVS
- 66.57
Essentials
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |