MFAP5
protein-codingmicrofibril associated protein 5
Gene summary
This gene encodes a 25-kD microfibril-associated glycoprotein which is a component of microfibrils of the extracellular matrix. The encoded protein promotes attachment of cells to microfibrils via alpha-V-beta-3 integrin. Deficiency of this gene in mice results in neutropenia. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014514
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0019625
Submitter: ClinGen
Inheritance Pattern: AD
Disease ID:MONDO:0014514
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0019625
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0014514
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular
Intervention: Cardiovascular
Rationale: Individual have been described with aortic dilatation and arrhthymias, and awareness may allow surveillance and early medical and/or surgical management, which may reduce morbidity and mortality
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MFAP5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003480.4. 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 | 3 | 52 | 55 | |||
| missense | 112 | 16 | 128 | |||
| nonsense | 1 | 1 | 6 | 8 | ||
| start loss | 1 | 1 | 2 | |||
| frameshift | 1 | 1 | 6 | 8 | ||
| splice donor/acceptor (+/-2bp) | 1 | 12 | 13 | |||
| Total | 2 | 4 | 140 | 68 | 0 | 214 |
Highest pathogenic variant AF is 0.000020523401
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003471.1 | 9 | MANE Select | |
| Ensembl | ENSP00000352455.2 | 9 | MANE Select | |
| RefSeq | NP_001284638.1 | 8 | Standard | |
| RefSeq | NP_001284639.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MFAP5-mediated ovarian cancer cell motility and invasiveness
- Extracellular matrix organization
- Molecules associated with elastic fibres
- Elastic fibre formation
- Notch signaling pathway
Biological Process
- extracellular matrix organization
- definitive hemopoiesis
- supramolecular fiber organization
Molecular Function
- extracellular matrix structural constituent
Cellular Component
- microfibril
- extracellular region
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359478
- Coding exons
- 9
- Length
- 25543
- Individuals with no LoFs
- 125716
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125747
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.322 | 96 | 105 | 0.912 | 0.00000619 | 1123 |
| Missense (PolyPhen) | 44 | 44.935 | 0.97919 | 460 | ||
| Synonymous | -0.600 | 39 | 34.5 | 1.13 | 0.00000190 | 323 |
| Loss of Function | 1.97 | 6 | 14.0 | 0.430 | 7.91e-7 | 147 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| 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: May play a role in hematopoiesis. In the cardiovascular system, could regulate growth factors or participate in cell signaling in maintaining large vessel integrity (By similarity). Component of the elastin-associated microfibrils (PubMed:8557636). {ECO:0000250|UniProtKB:Q9QZJ6, ECO:0000269|PubMed:8557636}.;
- Disease
- DISEASE: Aortic aneurysm, familial thoracic 9 (AAT9) [MIM:616166]: A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:25434006}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.511
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |