MFAP5

Summary

MFAP5 (microfibril associated protein 5, HGNC:29673) is a protein-coding gene on chromosome 12p13.31, encoding Microfibrillar-associated protein 5 (Q13361). May play a role in hematopoiesis.

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.

Source: NCBI Gene 8076 — RefSeq curated summary.

At a glance

• Gene–disease (curated): aortic aneurysm, familial thoracic 9 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 273 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 52
• MANE Select transcript: NM_003480

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29673
Approved symbol	MFAP5
Name	microfibril associated protein 5
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	MAGP2, MP25
Ensembl gene	ENSG00000197614
Ensembl biotype	protein_coding
OMIM	601103
Entrez	8076

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000359478, ENST00000396549, ENST00000433590, ENST00000534833, ENST00000535336, ENST00000535411, ENST00000537009, ENST00000537128, ENST00000538107, ENST00000538694, ENST00000543369, ENST00000543467, ENST00000544211, ENST00000544889, ENST00000856657, ENST00000856658, ENST00000952197, ENST00000952198, ENST00000952199, ENST00000952200

RefSeq mRNA: 5 — MANE Select: NM_003480 NM_001297709, NM_001297710, NM_001297711, NM_001297712, NM_003480

CCDS: CCDS73437, CCDS76522, CCDS76523, CCDS76524, CCDS8595

Canonical transcript exons

ENST00000359478 — 10 exons

Exon	Start	End
ENSE00001181279	8662627	8662826
ENSE00001411401	8645943	8648203
ENSE00003470089	8650502	8650589
ENSE00003554439	8655415	8655447
ENSE00003585675	8651662	8651691
ENSE00003595861	8662047	8662106
ENSE00003628252	8649501	8649574
ENSE00003634242	8660863	8660898
ENSE00003650359	8655786	8655830
ENSE00003661007	8654437	8654481

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.37.

FANTOM5 (CAGE): breadth broad, TPM avg 111.1493 / max 4175.3104, expressed in 767 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129367	33.5824	614
129364	28.1683	616
129365	23.8824	605
129366	20.9042	581
129368	2.1144	273
129351	1.0948	283
129357	0.5081	174
129348	0.3287	134
129361	0.1938	90
129350	0.1550	82

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	99.37	gold quality
skin of hip	UBERON:0001554	98.83	gold quality
tibial nerve	UBERON:0001323	98.49	gold quality
smooth muscle tissue	UBERON:0001135	98.13	gold quality
pericardium	UBERON:0002407	97.90	gold quality
placenta	UBERON:0001987	97.89	gold quality
right coronary artery	UBERON:0001625	97.79	gold quality
vena cava	UBERON:0004087	97.70	gold quality
urethra	UBERON:0000057	97.55	gold quality
decidua	UBERON:0002450	97.48	gold quality
tendon of biceps brachii	UBERON:0008188	97.34	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.24	gold quality
saphenous vein	UBERON:0007318	97.21	gold quality
myometrium	UBERON:0001296	96.62	gold quality
calcaneal tendon	UBERON:0003701	96.58	gold quality
diaphragm	UBERON:0001103	96.54	gold quality
coronary artery	UBERON:0001621	96.41	gold quality
left coronary artery	UBERON:0001626	96.33	gold quality
tendon	UBERON:0000043	96.25	gold quality
adipose tissue	UBERON:0001013	95.97	gold quality
rectum	UBERON:0001052	95.52	gold quality
connective tissue	UBERON:0002384	95.26	gold quality
penis	UBERON:0000989	94.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.01	gold quality
superficial temporal artery	UBERON:0001614	93.94	gold quality
lower esophagus	UBERON:0013473	93.93	gold quality
dorsal root ganglion	UBERON:0000044	93.68	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	4540.57
E-HCAD-36	yes	3300.88
E-HCAD-23	yes	1033.57
E-MTAB-10290	yes	656.11
E-MTAB-6701	yes	86.06
E-HCAD-1	yes	19.72
E-MTAB-6678	yes	18.12
E-HCAD-11	yes	10.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

129 targeting MFAP5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 29)

• microfibrillar proteins MAGP-1 and MAGP-2 can function outside of their role in elastic fibers to activate a cellular signaling pathway (PMID:16492672)
• MAGP-2 promotes angiogenic cell spouting in vitro by antagonizing Notch signaling pathways in endothelial cells. (PMID:18417156)
• Independent evaluation confirmed the association of a prognostic gene microfibril-associated glycoprotein 2 (MAGP2) with poor prognosis in advanced ovarian cancer (PMID:19962670)
• The MAGP2-based assay provided superior performance for the purpose of cell culture identification compared to assays using standard reference genes. (PMID:20345228)
• Decreased MFAP5 gene expression in the endometrium of patients with implantation failure after in vitro ertilization treatment (PMID:22885067)
• EPS led to the discovery of two novel immunomodulatory proteins, MFAP5 and PENK that when administered to mice subjected to endotoxemic shock, reversed the cytokine storm and provided a significant survival benefit (PMID:24496384)
• FAK/CREB/TNNC1 has a role in mediating the effect of stromal MFAP5 on ovarian cancer metastatic potential (PMID:25277212)
• Alteration of MAGP-2, a component of microfibrils and elastic fibers, appears as an initiating mechanism of inherited Thoracic aortic aneurysm and dissection (TAAD). (PMID:25434006)
• Our results demonstrate that factors involving low-grade inflammation modulate MFAP5 expression and that the modified expression of MFAP5 may further regulate adipose tissue inflammation. (PMID:26054006)
• The results answer the question of how MAGP2 controls cell type dependent Notch signaling, but more importantly uncover a new mechanism to understand how extracellular matrices and cellular environments impact Notch signaling. (PMID:26808411)
• Likely pathogenic variants included a TGFB2 variant in one patient and a SMAD3 variant in another. These variants have been reported previously in individuals with similar phenotypes. Variants of uncertain significance of particular interest included novel variants in MYLK and MFAP5, which were identified in a third patient (PMID:26854089)
• Study shows that over-expression of MFAP5 and TNNC1 is correlated with cervical lymph node metastasis (CLNM), metastasis relapse-free survival and overall survival. These results propose that MFAP5 and TNNC1 may be potential markers for predicting occult cervical lymphatic metastasis and prognosis of oral tongue carcinoma. (PMID:27713166)
• Data show that MAGP-2, component of the extracellular matrix interact with fibrillin and impart unique biological properties that influence microfibril function. Mutations in MAGP-2 have been linked to thoracic aneurysms and metabolic diseases and was shown to be an important biomarker in several human cancers. Also, mice lacking MAGP-2 have defects in multiple organ systems. [review] (PMID:29524629)
• MFAP5 was up-regulated in breast cancers compared with that in normal breast tissues, and further increased in breast cancer bone metastasis. Functionally, MFAP5 overexpression accelerated breast cancer cell proliferation and migration, while an opposite effect was observed when MFAP5 was knocked down. (PMID:29526753)
• Using in vitro assays, we demonstrated that MFAP5 activated OTSCC ( Oral Tongue Squamous Cell Carcinoma) cell growth and migration via activation of MAPK and AKT pathways. Using a tissue microarray of richly annotated primary human OTSCCs, we demonstrated an association of MFAP5 expression with patient survival. (PMID:29681158)
• We identified several potential key players contributing to extracellular matrix remodeling in varicose veins. Specifically, our analysis suggests MFAP5 acting as a master regulator, upstream of integrins, of the cellular network affecting the varicose vein condition. (PMID:30070582)
• this study showed that MFAP5 is a novel myoepithelial cell marker that appears to be upregulated in duct epithelium in duct carcinoma in situ and invasive carcinoma of no special type during tumorogenesis (PMID:30320661)
• This study identified a critical role played by MFAP5 in the progression of cervical cancer. (PMID:30454902)
• Stromal fibroblast-derived MFAP5 promotes the invasion and migration of breast cancer cells via Notch1/slug signaling. (PMID:31190277)
• Anticancer Immunotherapy by MFAP5 Blockade Inhibits Fibrosis and Enhances Chemosensitivity in Ovarian and Pancreatic Cancer. (PMID:31332047)
• MFAP5 is a useful marker that may help distinguish normal connective tissue from stroma within invasive colonic adenocarcinoma (PMID:31422503)
• Microfibrial-associated glycoprotein 2(MAGP2) negatively modulated by miR-200b-3p, is an oncogene of colorectal cancer associated with patients’ prognosis. It may function as a potential biomarker and therapeutic target for colorectal cancer (PMID:31426719)
• Authors showed that MFAP5 promoted ICC cell growth and G1 to S-phase transition. Using RNA-seq expression and ATAC-seq chromatin accessibility profiling of ICC cells with suppressed MFAP5 secretion, we showed that MFAP5 regulated the expression of genes involved in the Notch1 signaling pathway. (PMID:31775892)
• CAFs-derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling. (PMID:32293074)
• Reduced MFAP5 expression in stroma of gallbladder adenocarcinoma and its potential diagnostic utility. (PMID:32895766)
• MAGP2 induces tumor progression by enhancing uPAR-mediated cell proliferation. (PMID:34915136)
• Microfibril-Associated Glycoprotein-2 Promoted Fracture Healing via Integrin alphavbeta3/PTK2/AKT Signaling. (PMID:36934797)
• Targeting MFAP5 in cancer-associated fibroblasts sensitizes pancreatic cancer to PD-L1-based immunochemotherapy via remodeling the matrix. (PMID:37156839)
• Loci cg06256735 and cg15815843 in the MFAP5 gene regulatory regions are hypomethylated in varicose veins apparently due to active demethylation. (PMID:38743016)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfap5	ENSDARG00000090560
mus_musculus	Mfap5	ENSMUSG00000030116
rattus_norvegicus	Mfap5	ENSRNOG00000015505

Paralogs (1): MFAP2 (ENSG00000117122)

Protein

Protein identifiers

Microfibrillar-associated protein 5 — Q13361 (reviewed: Q13361)

Alternative names: MP25, Microfibril-associated glycoprotein 2

All UniProt accessions (9): B3KW70, Q13361, F5GYX4, F5H1C0, F5H2W4, F5H413, F5H7Z2, H0YG03, H0YGS3

UniProt curated annotations — full annotation on UniProt →

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. Component of the elastin-associated microfibrils.

Subunit / interactions. Interacts with TGFB2. Interacts with BMP2. Interacts with FBN1 (via N-terminal domain) and FBN2.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. Forms intermolecular disulfide bonds either with other MAGP-2 molecules or with other components of the microfibrils. N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. O-glycan heterogeneity at Thr-54: HexHexNAc (major) and HexHexNAc + sulfate (minor).

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the MFAP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13361-1	1	yes
Q13361-2	2

RefSeq proteins (5): NP_001284638, NP_001284639, NP_001284640, NP_001284641, NP_003471* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008673	MAGP	Family

Pfam: PF05507

UniProt features (8 total): glycosylation site 2, sequence variant 2, signal peptide 1, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13361-F1	65.79	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 54, 79

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1566948	Elastic fibre formation
R-HSA-2129379	Molecules associated with elastic fibres
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 300 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGACCTY_ERR1_Q2, ONDER_CDH1_TARGETS_3_DN, GRANDVAUX_IRF3_TARGETS_DN, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, MARTINEZ_RB1_TARGETS_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, SOX9_B1, MARTINEZ_RB1_TARGETS_DN, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, HUPER_BREAST_BASAL_VS_LUMINAL_UP, BASSO_HAIRY_CELL_LEUKEMIA_UP, PETRETTO_CARDIAC_HYPERTROPHY

GO Biological Process (3): embryonic eye morphogenesis (GO:0048048), definitive hemopoiesis (GO:0060216), supramolecular fiber organization (GO:0097435)

GO Molecular Function (1): extracellular matrix structural constituent (GO:0005201)

GO Cellular Component (3): microfibril (GO:0001527), extracellular region (GO:0005576), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Extracellular matrix organization	1
Elastic fibre formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
embryonic organ morphogenesis	1
eye morphogenesis	1
hemopoiesis	1
cellular component organization	1
structural molecule activity	1
extracellular matrix	1
elastic fiber	1
supramolecular fiber	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFAP5	FBN1	P35555	939
MFAP5	FBN2	P35556	879
MFAP5	JAG2	Q9Y219	812
MFAP5	MEGF6	O75095	714
MFAP5	DLL1	O00548	707
MFAP5	MFAP2	P55001	703
MFAP5	ELN	P15502	664
MFAP5	LTBP2	Q14767	606
MFAP5	COL1A1	P02452	589
MFAP5	FBLN5	Q9UBX5	581
MFAP5	EFEMP2	O95967	541
MFAP5	LOXL1	Q08397	540
MFAP5	EGF	P01133	522
MFAP5	FOXE3	Q13461	509
MFAP5	COL3A1	P02461	507

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MFAP5	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): VWDE (Affinity Capture-MS), ZNF507 (Affinity Capture-MS), TRPC4AP (Affinity Capture-MS), NOTCH3 (Affinity Capture-MS), LDLR (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), PASK (Affinity Capture-MS), CTU1 (Affinity Capture-MS), GALNT18 (Affinity Capture-MS), LAMA5 (Affinity Capture-MS), MIOS (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), ASB3 (Affinity Capture-MS), NEO1 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HTT5, A2BD09, A4IIT5, A6QLD2, F1N4E5, F1Q930, O14525, O18738, O35181, O73683, O75129, O93279, P05067, P08592, P12023, P15943, P29788, P53601, P79307, Q06335, Q06481, Q13361, Q28685, Q29243, Q3UZZ4, Q3V1G4, Q5EGE1, Q5IS80, Q5JTV8, Q5PQX1, Q5QQ37, Q5R7A3, Q60495, Q61137, Q62165, Q68BL7, Q68BL8, Q6L8S8, Q6QD51, Q701R2

Diamond homologs: P27424, P55001, P55002, Q13361, Q28022, Q9QZJ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

273 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	122
Likely benign	85
Benign	38

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1965449	NM_003480.4(MFAP5):c.236dup (p.Asn79fs)	Pathogenic
2445859	NM_003480.4(MFAP5):c.59-1G>C	Likely pathogenic
2581013	NM_003480.4(MFAP5):c.264del (p.Lys88fs)	Likely pathogenic

SpliceAI

1638 predictions. Top by Δscore:

Variant	Effect	Δscore
12:8648199:CTCAT:C	acceptor_gain	1.0000
12:8648201:CAT:C	acceptor_gain	1.0000
12:8649593:CA:C	acceptor_gain	1.0000
12:8649594:A:C	acceptor_gain	1.0000
12:8649600:A:T	acceptor_gain	1.0000
12:8655780:G:C	donor_gain	1.0000
12:8655781:CTTA:C	donor_loss	1.0000
12:8655782:TTA:T	donor_loss	1.0000
12:8655784:A:AC	donor_gain	1.0000
12:8655785:C:CA	donor_gain	1.0000
12:8655785:CT:C	donor_gain	1.0000
12:8655827:TCGT:T	acceptor_gain	1.0000
12:8655827:TCGTC:T	acceptor_loss	1.0000
12:8655828:CGT:C	acceptor_gain	1.0000
12:8655828:CGTC:C	acceptor_gain	1.0000
12:8655829:GT:G	acceptor_gain	1.0000
12:8655829:GTCTG:G	acceptor_loss	1.0000
12:8655830:TC:T	acceptor_loss	1.0000
12:8655831:C:CA	acceptor_loss	1.0000
12:8655831:C:CC	acceptor_gain	1.0000
12:8662626:CTGT:C	donor_gain	1.0000
12:8648200:TCAT:T	acceptor_gain	0.9900
12:8648201:CATC:C	acceptor_gain	0.9900
12:8648202:ATCTA:A	acceptor_loss	0.9900
12:8648203:TC:T	acceptor_loss	0.9900
12:8648204:C:CC	acceptor_gain	0.9900
12:8648204:CTAGA:C	acceptor_loss	0.9900
12:8648205:T:G	acceptor_loss	0.9900
12:8649585:CCCAG:C	acceptor_gain	0.9900
12:8649586:CCAG:C	acceptor_gain	0.9900

AlphaMissense

1130 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:8650570:A:C	F89L	0.996
12:8650570:A:T	F89L	0.996
12:8650571:A:C	F89C	0.996
12:8650572:A:G	F89L	0.996
12:8649539:C:G	C124S	0.995
12:8649540:A:T	C124S	0.995
12:8649524:C:G	C129S	0.994
12:8649525:A:T	C129S	0.994
12:8650565:C:T	C91Y	0.994
12:8648194:C:G	C140S	0.993
12:8648195:A:T	C140S	0.993
12:8649538:G:C	C124W	0.993
12:8649539:C:T	C124Y	0.993
12:8650564:G:C	C91W	0.993
12:8650565:C:G	C91S	0.992
12:8650566:A:T	C91S	0.992
12:8649525:A:G	C129R	0.991
12:8649540:A:G	C124R	0.991
12:8650566:A:G	C91R	0.991
12:8649524:C:T	C129Y	0.990
12:8648191:C:G	R141P	0.988
12:8649533:C:G	R126P	0.987
12:8650526:C:G	C104S	0.987
12:8650527:A:T	C104S	0.987
12:8650586:C:G	C84S	0.987
12:8650587:A:T	C84S	0.987
12:8648192:G:T	R141S	0.986
12:8648193:G:C	C140W	0.986
12:8648194:C:T	C140Y	0.986
12:8648195:A:G	C140R	0.986

dbSNP variants (sampled 300 via entrez): RS1000049704 (12:8659603 C>G), RS1000087853 (12:8649392 T>C), RS1000335943 (12:8646877 C>T), RS1000343237 (12:8653314 T>C), RS1000452078 (12:8647088 G>A,T), RS1000905986 (12:8660431 C>G), RS1000950364 (12:8651754 C>T), RS1001041794 (12:8664568 G>A), RS1001054130 (12:8658017 T>C), RS1001194843 (12:8656026 A>G), RS1001236161 (12:8653940 C>A,T), RS1001247259 (12:8647421 T>G), RS1001286207 (12:8658355 A>T), RS1001385593 (12:8660313 T>C), RS1001855819 (12:8653667 C>A)

Disease associations

OMIM: gene MIM:601103 | disease phenotypes: MIM:616166, MIM:607086

GenCC curated gene-disease

Disease	Classification	Inheritance
aortic aneurysm, familial thoracic 9	Strong	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Moderate	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
familial thoracic aortic aneurysm and aortic dissection	Moderate	AD

Mondo (3): aortic aneurysm, familial thoracic 9 (MONDO:0014514), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), connective tissue disorder (MONDO:0003900)

Orphanet (1): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000525	Abnormality iris morphology
HP:0000766	Abnormal sternum morphology
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000822	Hypertension
HP:0000965	Cutis marmorata
HP:0000978	Bruising susceptibility
HP:0001166	Arachnodactyly
HP:0001297	Stroke
HP:0001519	Disproportionate tall stature
HP:0001634	Mitral valve prolapse
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001763	Pes planus
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002138	Subarachnoid hemorrhage
HP:0002140	Ischemic stroke
HP:0002326	Transient ischemic attack
HP:0002616	Aortic root aneurysm
HP:0002647	Aortic dissection

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects splicing, decreases expression, increases abundance, increases expression	4
chloropicrin	decreases expression	2
bisphenol S	affects cotreatment, increases methylation, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Estradiol	increases expression, decreases expression, affects cotreatment	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
bisphenol A	increases expression	1
manganese chloride	increases abundance, increases expression	1
triadimefon	decreases expression	1
mercuric bromide	affects cotreatment, increases expression	1
tebuconazole	decreases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	affects expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression	1
Mercury	increases expression	1
Progesterone	decreases expression, affects cotreatment	1
Silicon Dioxide	increases expression	1

Clinical trials (associated diseases)

86 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	PHASE1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	PHASE1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	PHASE1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	PHASE1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT05636527	Not specified	RECRUITING	Further Evaluation of Safety and Performance of the NEXUS Aortic Arch Stent Graft System and the Custom-Made NEXUS Multibranch™ Aortic Arch Stent Graft System
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT06783803	Not specified	ACTIVE_NOT_RECRUITING	Application of Linkage Analysis in the Identification of Novel Hereditary Factors in Familial Aneurysms
NCT01424033	PHASE2/PHASE3	TERMINATED	A Clinical Trial for CTD-ILD Treatment
NCT04915482	PHASE2/PHASE3	UNKNOWN	TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT06574581	PHASE1/PHASE2	RECRUITING	ADSCs Therapy in Patients With CTD-ILD
NCT00001330	Not specified	COMPLETED	Study of Silicone-Associated Connective Tissue Diseases
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00001978	Not specified	TERMINATED	Determination of Kidney Function
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease