THSD4

Summary

THSD4 (thrombospondin type 1 domain containing 4, HGNC:25835) is a protein-coding gene on chromosome 15q23, encoding Thrombospondin type-1 domain-containing protein 4 (Q6ZMP0). Promotes FBN1 matrix assembly.

Predicted to enable hydrolase activity. Predicted to be an extracellular matrix structural constituent. Involved in microfibril assembly. Located in microfibril. Implicated in thoracic aortic aneurysm.

Source: NCBI Gene 79875 — RefSeq curated summary.

At a glance

• Gene–disease (curated): aortic aneurysm, familial thoracic 12 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 38
• Clinical variants (ClinVar): 260 total — 5 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 53
• MANE Select transcript: NM_024817

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25835
Approved symbol	THSD4
Name	thrombospondin type 1 domain containing 4
Location	15q23
Locus type	gene with protein product
Status	Approved
Aliases	FVSY9334, PRO34005, FLJ13710, ADAMTSL6
Ensembl gene	ENSG00000187720
Ensembl biotype	protein_coding
OMIM	614476
Entrez	79875

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000261862, ENST00000355327, ENST00000357769, ENST00000567745, ENST00000567776, ENST00000567838, ENST00000620694

RefSeq mRNA: 3 — MANE Select: NM_024817 NM_001286429, NM_001394532, NM_024817

CCDS: CCDS10238, CCDS66817

Canonical transcript exons

ENST00000261862 — 18 exons

Exon	Start	End
ENSE00000697095	71771064	71771208
ENSE00001483237	71411687	71411823
ENSE00001483238	71256613	71256715
ENSE00001483239	71242649	71243096
ENSE00001483241	71215035	71215399
ENSE00001483243	71154863	71154932
ENSE00001535272	71141449	71141556
ENSE00001535281	71777232	71783383
ENSE00003479953	71728549	71728724
ENSE00003495741	71748421	71748594
ENSE00003499251	71746838	71747042
ENSE00003526090	71757902	71758075
ENSE00003597048	71731121	71731217
ENSE00003630333	71737732	71738007
ENSE00003637945	71765020	71765199
ENSE00003654924	71745106	71745235
ENSE00003670857	71660530	71660734
ENSE00003938769	71115471	71115698

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9933 / max 563.5207, expressed in 1373 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147516	10.5261	1287
147540	1.2056	186
147515	0.8592	473
147542	0.8373	361
147509	0.2313	79
147510	0.1448	57
147523	0.0677	22
147521	0.0617	21
147541	0.0513	22
147539	0.0082	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.80	gold quality
esophagus squamous epithelium	UBERON:0006920	96.84	gold quality
secondary oocyte	CL:0000655	96.63	gold quality
mammalian vulva	UBERON:0000997	95.34	gold quality
trigeminal ganglion	UBERON:0001675	95.34	gold quality
nipple	UBERON:0002030	95.07	gold quality
urethra	UBERON:0000057	94.45	gold quality
esophagus mucosa	UBERON:0002469	93.42	gold quality
right uterine tube	UBERON:0001302	92.66	gold quality
apex of heart	UBERON:0002098	92.27	gold quality
decidua	UBERON:0002450	91.74	gold quality
penis	UBERON:0000989	91.54	gold quality
vagina	UBERON:0000996	90.99	gold quality
epithelium of esophagus	UBERON:0001976	90.92	gold quality
cardiac ventricle	UBERON:0002082	90.79	gold quality
heart left ventricle	UBERON:0002084	90.78	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.31	gold quality
mammary duct	UBERON:0001765	90.11	gold quality
prostate gland	UBERON:0002367	89.91	gold quality
descending thoracic aorta	UBERON:0002345	89.57	gold quality
visceral pleura	UBERON:0002401	89.43	gold quality
endocervix	UBERON:0000458	89.35	gold quality
heart right ventricle	UBERON:0002080	89.28	gold quality
germinal epithelium of ovary	UBERON:0001304	88.98	gold quality
thoracic aorta	UBERON:0001515	88.75	gold quality
ascending aorta	UBERON:0001496	88.63	gold quality
lower esophagus mucosa	UBERON:0035834	88.63	gold quality
jejunal mucosa	UBERON:0000399	88.30	gold quality
dorsal root ganglion	UBERON:0000044	87.90	gold quality
stromal cell of endometrium	CL:0002255	87.79	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	4412.69
E-CURD-119	yes	1434.06
E-HCAD-35	yes	22.98
E-ANND-3	yes	14.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

167 targeting THSD4, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390

Literature-anchored findings (GeneRIF, showing 6)

• Variations may be important determinants of osteoporosis in Japanese women. (PMID:18488137)
• Data show expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in lung tissue and indicate potential targets for interventions to alleviate respiratory disease. (PMID:20010834)
• ADAMTSL6beta has a role in fibrillin-1 microfibril formation (PMID:21880733)
• THSD4 polymorphism was not found to be associated with COPD risk (PMID:21965014)
• In breast cancer, some GATA3 effects shift from tumor suppressing to tumor promoting during tumorigenesis, with deregulation of three genes, BCL2, DACH1, THSD4, representing major GATA3-controlled processes in cancer progression. (PMID:25410484)
• ZNF37A promotes tumor metastasis through transcriptional control of THSD4/TGF-beta axis in colorectal cancer. (PMID:33875786)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Thsd4	ENSMUSG00000032289
rattus_norvegicus	Thsd4	ENSRNOG00000053753

Paralogs (25): ADAMTS6 (ENSG00000049192), ADAMTS2 (ENSG00000087116), PAPLN (ENSG00000100767), ADAMTS8 (ENSG00000134917), ADAMTS7 (ENSG00000136378), ADAMTS14 (ENSG00000138316), ADAMTS17 (ENSG00000140470), ADAMTS18 (ENSG00000140873), ADAMTS10 (ENSG00000142303), ADAMTSL4 (ENSG00000143382), ADAMTS16 (ENSG00000145536), ADAMTS19 (ENSG00000145808), ADAMTS12 (ENSG00000151388), ADAMTS1 (ENSG00000154734), ADAMTS5 (ENSG00000154736), ADAMTS3 (ENSG00000156140), ADAMTSL3 (ENSG00000156218), ADAMTS4 (ENSG00000158859), ADAMTS13 (ENSG00000160323), ADAMTS9 (ENSG00000163638), ADAMTS15 (ENSG00000166106), ADAMTS20 (ENSG00000173157), ADAMTSL1 (ENSG00000178031), ADAMTSL5 (ENSG00000185761), ADAMTSL2 (ENSG00000197859)

Protein

Protein identifiers

Thrombospondin type-1 domain-containing protein 4 — Q6ZMP0 (reviewed: Q6ZMP0)

Alternative names: A disintegrin and metalloproteinase with thrombospondin motifs-like protein 6

All UniProt accessions (2): A0A087X1T0, Q6ZMP0

UniProt curated annotations — full annotation on UniProt →

Function. Promotes FBN1 matrix assembly. Attenuates TGFB signaling, possibly by accelerating the sequestration of large latent complexes of TGFB or active TGFB by FBN1 microfibril assembly, thereby negatively regulating the expression of TGFB regulatory targets, such as POSTN.

Subunit / interactions. Interacts with FBN1. May interact with TGFB1.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Disease relevance. Aortic aneurysm, familial thoracic 12 (AAT12) [MIM:619825] A form of thoracic aortic aneurysm, 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. AAT12 is an autosomal dominant disease manifesting with aortic dissection and progressive dilation of the aortic root, ascending aorta, and abdominal aorta. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6ZMP0-1	1	yes
Q6ZMP0-2	2
Q6ZMP0-3	3
Q6ZMP0-4	4

RefSeq proteins (3): NP_001273358, NP_001381461, NP_079093* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR010294	ADAMTS_spacer1	Domain
IPR010909	PLAC	Domain
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR045371	ADAMTS_CR_3	Domain
IPR050439	ADAMTS_ADAMTS-like	Family

Pfam: PF00090, PF05986, PF08686, PF19030, PF19236

UniProt features (31 total): splice variant 8, domain 7, compositionally biased region 5, region of interest 3, sequence variant 3, sequence conflict 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMP0-F1	67.29	0.14

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
R-HSA-1643685	Disease
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 247 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOZGIT_ESR1_TARGETS_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_EXTRACELLULAR_MATRIX_ASSEMBLY, CHANDRAN_METASTASIS_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, chr15q23, VECCHI_GASTRIC_CANCER_EARLY_DN, HAN_SATB1_TARGETS_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, YNGTTNNNATT_UNKNOWN, THUM_SYSTOLIC_HEART_FAILURE_DN

GO Biological Process (3): elastic fiber assembly (GO:0048251), microfibril assembly (GO:0160054), supramolecular fiber organization (GO:0097435)

GO Molecular Function (2): hydrolase activity (GO:0016787), extracellular matrix structural constituent (GO:0005201)

GO Cellular Component (4): microfibril (GO:0001527), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
supramolecular fiber organization	2
extracellular matrix assembly	1
cellular component assembly	1
cellular component organization	1
catalytic activity	1
structural molecule activity	1
extracellular matrix	1
elastic fiber	1
supramolecular fiber	1
external encapsulating structure	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THSD4	GSTCD	Q8NEC7	703
THSD4	FAM13A	O94988	601
THSD4	INTS12	Q96CB8	571
THSD4	PID1	Q7Z2X4	544
THSD4	SIM2	Q14190	529
THSD4	LRMDA	Q9H2I8	515
THSD4	TNS1	Q9HBL0	506
THSD4	HHIP	Q96QV1	506
THSD4	FBN1	P35555	482
THSD4	NPNT	Q6UXI9	480
THSD4	ADAMTS10	Q9H324	451
THSD4	ADAM19	Q9H013	450
THSD4	ADGRG6	Q86SQ4	449
THSD4	CYRIB	Q9NUQ9	449
THSD4	PPT2	Q9UMR5	447

IntAct

29 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
THSD4	KRBA1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KANSL1	ECI2	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
NCR3	POTEF	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
EDN3	POTEF	psi-mi:“MI:0914”(association)	0.350
LOXL4	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
PI15		psi-mi:“MI:0914”(association)	0.350
FHL3		psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350
NXPH3	ACACB	psi-mi:“MI:0914”(association)	0.350
BCAN	LAMA5	psi-mi:“MI:0914”(association)	0.350
CDHR4	TAPBP	psi-mi:“MI:0914”(association)	0.350
UQCC1	MGRN1	psi-mi:“MI:0914”(association)	0.350
TRIM68	TJP1	psi-mi:“MI:0914”(association)	0.350
NPTX1	NPTXR	psi-mi:“MI:0914”(association)	0.350
EPDR1	DUSP14	psi-mi:“MI:0914”(association)	0.350
	THSD4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (64): ZNF195 (Affinity Capture-MS), ALMS1 (Affinity Capture-MS), KRBA1 (Affinity Capture-MS), CEP164 (Affinity Capture-MS), GLI3 (Affinity Capture-MS), ZNF609 (Affinity Capture-MS), FOXG1 (Affinity Capture-MS), APPBP2 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), USP54 (Affinity Capture-MS), OFD1 (Affinity Capture-MS), RIPK1 (Affinity Capture-MS), ARID5B (Affinity Capture-MS), MLF1 (Affinity Capture-MS), NUFIP2 (Affinity Capture-MS)

ESM2 similar proteins: A7MBS7, D3YXF5, F1LW30, O89103, P10643, P11680, P27918, P35446, P82987, P90884, Q29RQ1, Q2I0M5, Q2MKA7, Q3UPR9, Q3UTY6, Q4R7Z5, Q5M7L6, Q5RAD0, Q5RBP1, Q5RBP8, Q5UE90, Q64181, Q66PY1, Q69ZU6, Q6NZL8, Q6P4U0, Q6UXX9, Q6ZMP0, Q7T3Q2, Q7TSK7, Q80YN4, Q86TH1, Q8BFU0, Q8BJ73, Q8BLI0, Q8IUX8, Q8IWY4, Q8IX30, Q8N6G6, Q8VCC9

Diamond homologs: A2VEC9, A6QLU6, B3EWY9, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, E9Q6D8, F1LW30, G5ECS8, O08721, O08722, O08747, O14514, O15072, O60241, O60242, O76840, O95185, O95428, O95450, P07358, P07996, P11680, P13671, P27918, P35440, P35441, P35442, P35446, P35448, P55314, P57110, P58397, P59384, P59510, P61134, P61135

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	186
Likely benign	26
Benign	14

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1069468	NM_024817.3(THSD4):c.314_317dup (p.Ala107fs)	Pathogenic
1675221	NM_024817.3(THSD4):c.740del (p.Pro246_Leu247insTer)	Pathogenic
1675223	NM_024817.3(THSD4):c.1402del (p.Ala468fs)	Pathogenic
1675224	NM_024817.3(THSD4):c.137_145dup (p.Asp46_Gly48dup)	Pathogenic
1675225	NM_024817.3(THSD4):c.961T>A (p.Tyr321Asn)	Pathogenic
2584577	Single allele	Likely pathogenic
2691038	NM_024817.3(THSD4):c.1533+1G>C	Likely pathogenic
3236718	NM_024817.3(THSD4):c.358G>T (p.Glu120Ter)	Likely pathogenic
3236719	NM_024817.3(THSD4):c.853C>T (p.Arg285Ter)	Likely pathogenic
3236720	NM_024817.3(THSD4):c.1902dup (p.Lys635fs)	Likely pathogenic

SpliceAI

5498 predictions. Top by Δscore:

Variant	Effect	Δscore
15:71115271:C:CA	donor_gain	1.0000
15:71115278:A:AC	donor_gain	1.0000
15:71115279:C:CC	donor_gain	1.0000
15:71115295:C:A	donor_gain	1.0000
15:71115329:T:TA	donor_gain	1.0000
15:71141444:CATA:C	acceptor_loss	1.0000
15:71141445:ATAG:A	acceptor_gain	1.0000
15:71141447:A:AG	acceptor_gain	1.0000
15:71141447:A:C	acceptor_loss	1.0000
15:71141447:AG:A	acceptor_gain	1.0000
15:71141448:G:GA	acceptor_gain	1.0000
15:71141448:G:GC	acceptor_loss	1.0000
15:71141448:GG:G	acceptor_gain	1.0000
15:71141555:AGGT:A	donor_loss	1.0000
15:71141557:G:C	donor_loss	1.0000
15:71141557:G:GG	donor_gain	1.0000
15:71141558:T:G	donor_loss	1.0000
15:71233120:G:GT	donor_gain	1.0000
15:71256610:TAGGT:T	acceptor_loss	1.0000
15:71256611:A:T	acceptor_loss	1.0000
15:71256612:GGTAT:G	acceptor_gain	1.0000
15:71411672:A:AG	acceptor_gain	1.0000
15:71411673:T:G	acceptor_gain	1.0000
15:71411677:A:AG	acceptor_gain	1.0000
15:71411677:ACTTT:A	acceptor_gain	1.0000
15:71411681:T:TA	acceptor_gain	1.0000
15:71411685:A:AG	acceptor_gain	1.0000
15:71411686:G:GA	acceptor_gain	1.0000
15:71411686:GTAA:G	acceptor_gain	1.0000
15:71411821:AAGG:A	donor_loss	1.0000

AlphaMissense

1413 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:71660675:T:C	I433T	0.999
15:71660719:A:C	S448R	0.999
15:71660721:C:A	S448R	0.999
15:71660721:C:G	S448R	0.999
15:71660539:T:A	C388S	0.998
15:71660539:T:C	C388R	0.998
15:71660540:G:A	C388Y	0.998
15:71660540:G:C	C388S	0.998
15:71660578:T:C	C401R	0.998
15:71660587:T:A	C404S	0.998
15:71660587:T:C	C404R	0.998
15:71660588:G:C	C404S	0.998
15:71660608:T:A	C411S	0.998
15:71660608:T:C	C411R	0.998
15:71660609:G:C	C411S	0.998
15:71660657:A:G	Y427C	0.998
15:71660675:T:G	I433S	0.998
15:71660686:G:C	A437P	0.998
15:71660687:C:A	A437D	0.998
15:71660696:T:G	I440S	0.998
15:71660720:G:T	S448I	0.998
15:71660578:T:A	C401S	0.997
15:71660579:G:C	C401S	0.997
15:71660656:T:G	Y427D	0.997
15:71660666:T:A	V430D	0.997
15:71660696:T:A	I440N	0.997
15:71660696:T:C	I440T	0.997
15:71660702:T:A	I442N	0.997
15:71660540:G:T	C388F	0.996
15:71660541:T:G	C388W	0.996

dbSNP variants (sampled 300 via entrez): RS1000000575 (15:71318110 T>C), RS1000007540 (15:71245881 G>C), RS1000021620 (15:71668686 T>C), RS1000024242 (15:71604488 G>A), RS1000025153 (15:71714867 C>A,T), RS1000025213 (15:71152341 G>C), RS1000033454 (15:71521548 C>A), RS1000034440 (15:71356815 C>A,T), RS1000037042 (15:71246172 C>G), RS1000039624 (15:71647442 A>G), RS1000042259 (15:71452172 G>A), RS1000050688 (15:71164513 G>A,T), RS1000051287 (15:71100529 G>A), RS1000051655 (15:71332994 C>G), RS1000054416 (15:71604811 GAAAACA>G)

Disease associations

OMIM: gene MIM:614476 | disease phenotypes: MIM:619825, MIM:607086

GenCC curated gene-disease

Disease	Classification	Inheritance
aortic aneurysm, familial thoracic 12	Strong	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Moderate	Autosomal dominant

Mondo (2): aortic aneurysm, familial thoracic 12 (MONDO:0030731), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625)

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

HPO phenotypes

53 total (30 of 53 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:0000822	Hypertension
HP:0000965	Cutis marmorata
HP:0000978	Bruising susceptibility
HP:0001166	Arachnodactyly
HP:0001297	Stroke
HP:0001369	Arthritis
HP:0001519	Disproportionate tall stature
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:0002108	Spontaneous 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

38 associations (top):

Study	Trait	p-value
GCST000544_1	Pulmonary function	7.000000e-15
GCST001621_16	Airflow obstruction	1.000000e-07
GCST001784_31	Pulmonary function (smoking interaction)	4.000000e-21
GCST002113_3	Pulmonary function	3.000000e-09
GCST002127_6	Periodontitis (Mean PAL)	7.000000e-06
GCST002136_16	Periodontitis (PAL4Q3)	7.000000e-06
GCST002136_2	Periodontitis (PAL4Q3)	2.000000e-06
GCST004147_12	Chronic obstructive pulmonary disease	8.000000e-16
GCST004185_38	Lung function (FEV1/FVC)	1.000000e-24
GCST004185_7	Lung function (FEV1/FVC)	6.000000e-10
GCST004379_11	Red blood cell density in sickle cell anemia	2.000000e-06
GCST005549_15	Alzheimer’s disease (late onset)	4.000000e-06
GCST006105_1	Eye morphology	2.000000e-07
GCST006105_8	Eye morphology	2.000000e-06
GCST007094_148	Diastolic blood pressure	1.000000e-08
GCST007268_52	Diastolic blood pressure	1.000000e-13
GCST007269_283	Pulse pressure	3.000000e-12
GCST007430_127	Peak expiratory flow	3.000000e-55
GCST007431_123	Lung function (FEV1/FVC)	4.000000e-145
GCST007431_124	Lung function (FEV1/FVC)	1.000000e-23
GCST007432_156	FEV1	4.000000e-21
GCST007432_157	FEV1	1.000000e-11
GCST007692_34	Chronic obstructive pulmonary disease	2.000000e-17
GCST007692_35	Chronic obstructive pulmonary disease	1.000000e-24
GCST007692_71	Chronic obstructive pulmonary disease	7.000000e-33
GCST008154_3	Trunk fat mass	2.000000e-07
GCST008155_58	Waist-hip ratio	5.000000e-06
GCST008157_25	Body fat mass	9.000000e-06
GCST008157_41	Body fat mass	4.000000e-07
GCST009723_90	Vertical cup-disc ratio (adjusted for vertical disc diameter)	5.000000e-07

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:1001870	late-onset Alzheimers disease
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009718	peak expiratory flow
EFO:0004314	forced expiratory volume
EFO:0004343	waist-hip ratio
EFO:0006939	cup-to-disc ratio measurement
EFO:0008007	age at assessment
EFO:0004346	neuroimaging measurement
EFO:0008336	disease progression measurement
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects methylation, affects cotreatment, increases expression	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, affects expression	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
bisphenol F	increases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation, increases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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