MFHAS1
protein-codingmultifunctional ROCO family signaling regulator 1, the group of ROCO family
Gene summary
Identified in a human 8p amplicon, this gene is a potential oncogene whose expression is enhanced in some malignant fibrous histiocytomas (MFH). The primary structure of its product includes an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, which are structural or functional elements for interactions among proteins related to the cell cycle, and which suggest that overexpression might be oncogenic with respect to MFH. [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 ~110.3 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 MFHAS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004225.3. 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 | 15 | 3 | 18 | |||
| missense | 204 | 5 | 1 | 210 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 206 | 21 | 4 | 231 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004216.2 | 3 | MANE Select | |
| Ensembl | ENSP00000276282.6 | 3 | MANE Select | |
| Ensembl | ENSP00000675155.1 | 3 | Standard | |
| Ensembl | ENSP00000749112.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- inflammatory response
- erythrocyte differentiation
- negative regulation of toll-like receptor 2 signaling pathway
- positive regulation of toll-like receptor 2 signaling pathway
- negative regulation of toll-like receptor 4 signaling pathway
Molecular Function
- protein binding
- GTP binding
- ubiquitin protein ligase binding
- protein phosphatase 2A binding
Cellular Component
- cytoplasm
- mitochondrion
- lysosome
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000276282
- Coding exons
- 3
- Length
- 110292
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125748
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.94 | 757 | 621 | 1.22 | 0.0000367 | 6660 |
| Missense (PolyPhen) | 215 | 225.79 | 0.95221 | 2573 | ||
| Synonymous | -5.73 | 415 | 291 | 1.43 | 0.0000178 | 2293 |
| Loss of Function | 2.36 | 19 | 33.8 | 0.562 | 0.00000202 | 338 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable GTP-binding protein (PubMed:24286120). Functions in innate immunity and more specifically the inflammatory response as a regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways (PubMed:26599367, PubMed:28471450, PubMed:28609714). Negatively regulates the part of the TLR4 signaling pathway that leads to the activation of the transcription factor AP-1. By retaining the phosphatase complex PP2A into the cytoplasm, prevents the dephosphorylation of the AP- 1 subunit JUN which is required for proper activation of the transcription factor (PubMed:28609714). Both inhibits and activates the TLR2-dependent signaling pathway (PubMed:26599367). Positively regulates the TLR2 signaling pathway to activate specifically the downstream p38 and JNK MAP kinases and promote the polarization of macrophages toward the pro-inflammatory M1 phenotype (PubMed:28471450). It may also play a role in the regulation of inflammation induced by high glucose through the PKB/AKT signaling pathway (PubMed:29168081). Also involved in erythrocyte differentiation through activation of the ERK1/ERK2 signaling pathway (PubMed:23327923). {ECO:0000269|PubMed:23327923, ECO:0000269|PubMed:24286120, ECO:0000269|PubMed:26599367, ECO:0000269|PubMed:28471450, ECO:0000269|PubMed:28609714, ECO:0000269|PubMed:29168081}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving MFHAS1 may be a cause of B-cell lymphoma. Translocation t(8;14)(p23.1;q21) with a cryptic exon named '14q21 element'. The resulting fusion protein named 'chimeric MASL1' is tumorigenic in nude mice. {ECO:0000269|PubMed:14691450}.;
Recessive Scores
- pRec
- 0.116
Intolerance Scores
- LoFtool
- 0.509
- RVIS EVS
- -1.19
- RVIS percentile EVS
- 5.89
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.410
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |