MFAP5

microfibril associated protein 5

Basic information

Region (hg38): 12:8637346-8662888

Links

ENSG00000197614

∙ NCBI:8076 ∙ OMIM:601103 ∙ HGNC:29673 ∙ Uniprot:Q13361 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

aortic aneurysm, familial thoracic 9 (Moderate), mode of inheritance: AD
aortic aneurysm, familial thoracic 9 (Limited), mode of inheritance: AD
familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
aortic aneurysm, familial thoracic 9 (Strong), mode of inheritance: AD
familial thoracic aortic aneurysm and aortic dissection (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aortic aneurysm, familial thoracic 9	AD	Cardiovascular	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	Cardiovascular	25434006

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MFAP5 gene.

not_provided (208 variants)
Cardiovascular_phenotype (113 variants)
not_specified (18 variants)
Aortic_aneurysm,_familial_thoracic_9 (13 variants)
MFAP5-related_disorder (13 variants)
Familial_thoracic_aortic_aneurysm_and_aortic_dissection (3 variants)
Isolated_thoracic_aortic_aneurysm (1 variants)
Connective_tissue_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MFAP5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003480.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	46 clinvar		49
missense			98 clinvar	14 clinvar		112
nonsense		3 clinvar	5 clinvar			8
start loss		1	1			2
frameshift		1 clinvar	6 clinvar			7
splice donor/acceptor (+/-2bp)		1 clinvar	8 clinvar			9
Total	0	6	121	60	0

Highest pathogenic variant AF is 0.0000205234

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MFAP5	protein_coding	protein_coding	ENST00000359478	9	25543

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00506	0.971	125716	0	31	125747	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.322	96	105	0.912	0.00000619	1123
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000908	0.000907
Ashkenazi Jewish	0.00	0.00
East Asian	0.000223	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000537	0.0000527
Middle Eastern	0.000223	0.000217
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

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.;
Pathway: MFAP5-mediated ovarian cancer cell motility and invasiveness;Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation;Notch signaling pathway (Consensus)

Recessive Scores

pRec: 0.103

Intolerance Scores

loftool: 0.511
rvis_EVS: -0.34
rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

pHI: 0.736
hipred: Y
hipred_score: 0.742
ghis: 0.584

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Mfap5
Phenotype: skeleton phenotype; immune system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype;

Gene ontology

Biological process: extracellular matrix organization;definitive hemopoiesis;supramolecular fiber organization
Cellular component: microfibril;extracellular region;collagen-containing extracellular matrix
Molecular function: extracellular matrix structural constituent