MACC1
protein-codingMET transcriptional regulator MACC1
Gene summary
MACC1 is a key regulator of the hepatocyte growth factor (HGF; MIM 142409)-HGF receptor (HGFR, or MET; MIM 164860) pathway, which is involved in cellular growth, epithelial-mesenchymal transition, angiogenesis, cell motility, invasiveness, and metastasis. Expression of MACC1 in colon cancer (MIM 114500) specimens is an independent prognostic indicator for metastasis formation and metastasis-free survival (Stein et al., 2009 [PubMed 19098908]).[supplied by OMIM, Mar 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~82.7 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 MACC1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182762.4. 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 | 1 | ||||
| missense | 126 | 8 | 134 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 127 | 8 | 0 | 135 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_877439.3 | 4 | MANE Select | |
| Ensembl | ENSP00000383185.3 | 4 | MANE Select | |
| Ensembl | ENSP00000328410.4 | 4 | Standard | |
| Ensembl | ENSP00000328410.4 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| macc1 | Danio rerio | Structure: ceratobranchial cartilage Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of signaling receptor activity
- positive regulation of transcription by RNA polymerase II
- positive regulation of cell division
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- growth factor activity
Cellular Component
- nucleus
- cytoplasm
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000400331
- Coding exons
- 4
- Length
- 82750
- Individuals with no LoFs
- 125464
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 278
- Defined
- 125744
- p
- 0.00111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.29 | 501 | 426 | 1.18 | 0.0000202 | 5578 |
| Missense (PolyPhen) | 138 | 112.32 | 1.2286 | 1512 | ||
| Synonymous | 0.279 | 152 | 156 | 0.972 | 0.00000773 | 1625 |
| Loss of Function | 0.283 | 29 | 30.7 | 0.945 | 0.00000147 | 423 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0024 | 0.0022 | notable |
| Latino/Admixed American | 0.00069 | 0.00067 | rare |
| Ashkenazi Jewish | 0.0049 | 0.0033 | notable |
| East Asian | 0.0025 | 0.0025 | notable |
| Finnish | 0.00042 | 0.00042 | rare |
| European (Non-Finnish) | 0.00055 | 0.00055 | rare |
| South Asian | 0.0022 | 0.0021 | notable |
| Other | 0.0010 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a transcription activator for MET and as a key regulator of HGF-MET signaling. Promotes cell motility, proliferation and hepatocyte growth factor (HGF)-dependent scattering in vitro and tumor growth and metastasis in vivo. {ECO:0000269|PubMed:19098908}.;
Recessive Scores
- pRec
- 0.0968
Intolerance Scores
- LoFtool
- 0.987
- RVIS EVS
- 1.81
- RVIS percentile EVS
- 96.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.299
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |