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.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	32		34
missense			83	4		87
nonsense		2	3			5
start loss			1			1
frameshift		1	3			4
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1	7			8
splice region			7	5	2	14
non coding			3	40	37	80
Total	0	4	104	76	37

Variants in MFAP5

This is a list of pathogenic ClinVar variants found in the MFAP5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-8647970-A-G			Benign (Jun 23, 2018)
12-8648077-C-G			Likely benign (Aug 23, 2017)
12-8648087-A-G		not specified	Benign/Likely benign (Aug 03, 2024)
12-8648094-C-T			Likely benign (Jun 02, 2021)
12-8648100-A-T		not specified	Uncertain significance (Jun 09, 2024)
12-8648101-T-C		Cardiovascular phenotype	Conflicting classifications of pathogenicity (May 23, 2023)
12-8648104-G-A			Uncertain significance (Mar 04, 2023)
12-8648106-T-C		Cardiovascular phenotype	Likely benign (Sep 21, 2019)
12-8648115-AT-A			Uncertain significance (Mar 04, 2022)
12-8648134-G-A		Cardiovascular phenotype	Uncertain significance (Oct 02, 2023)
12-8648135-G-A			Uncertain significance (Nov 17, 2023)
12-8648139-T-C		Cardiovascular phenotype	Likely benign (Nov 08, 2020)
12-8648140-C-A			Uncertain significance (Jun 26, 2024)
12-8648140-C-T		Cardiovascular phenotype	Uncertain significance (Nov 21, 2023)
12-8648141-G-A		Aortic aneurysm, familial thoracic 9 • Isolated thoracic aortic aneurysm	Conflicting classifications of pathogenicity (Jul 17, 2023)
12-8648149-T-C			Uncertain significance (Sep 04, 2023)
12-8648150-T-C			Uncertain significance (Jul 14, 2022)
12-8648155-C-T		Cardiovascular phenotype	Uncertain significance (May 10, 2024)
12-8648158-C-T		MFAP5-related disorder	Uncertain significance (Apr 01, 2023)
12-8648159-G-A			Likely benign (Jan 01, 2024)
12-8648159-G-T		Cardiovascular phenotype	Uncertain significance (Jun 10, 2022)
12-8648162-G-A		Cardiovascular phenotype	Uncertain significance (Nov 28, 2021)
12-8648164-C-G			Uncertain significance (Oct 01, 2021)
12-8648167-C-A		Cardiovascular phenotype	Uncertain significance (Apr 24, 2023)
12-8648168-TA-T		Cardiovascular phenotype	Uncertain significance (Jun 20, 2024)

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