MIA3

Summary

MIA3 (MIA SH3 domain ER export factor 3, HGNC:24008) is a protein-coding gene on chromosome 1q41, encoding Transport and Golgi organization protein 1 homolog (Q5JRA6). Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum.

Enables cargo receptor activity. Involved in several processes, including COPII-coated vesicle cargo loading; cell migration involved in sprouting angiogenesis; and regulation of leukocyte migration. Located in endoplasmic reticulum exit site and endoplasmic reticulum membrane.

Source: NCBI Gene 375056 — RefSeq curated summary.

At a glance

• Gene–disease (curated): odontochondrodysplasia 2 with hearing loss and diabetes (Strong, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 332 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 28
• Druggable target: yes
• MANE Select transcript: NM_198551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24008
Approved symbol	MIA3
Name	MIA SH3 domain ER export factor 3
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	UNQ6077, FLJ39207, KIAA0268, TANGO, TANGO1
Ensembl gene	ENSG00000154305
Ensembl biotype	protein_coding
OMIM	613455
Entrez	375056

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 7 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000340535, ENST00000344922, ENST00000354906, ENST00000450260, ENST00000467190, ENST00000470521, ENST00000475451, ENST00000476400, ENST00000477519, ENST00000479370, ENST00000495210, ENST00000883516, ENST00000929360, ENST00000929361, ENST00000929362, ENST00000929363, ENST00000957134

RefSeq mRNA: 6 — MANE Select: NM_198551 NM_001300867, NM_001324062, NM_001324063, NM_001324064, NM_001324065, NM_198551

CCDS: CCDS41470, CCDS73035

Canonical transcript exons

ENST00000344922 — 28 exons

Exon	Start	End
ENSE00001862211	222618097	222618243
ENSE00001893417	222665309	222668007
ENSE00002211537	222653228	222653339
ENSE00002214215	222653008	222653130
ENSE00002219374	222652228	222652332
ENSE00002247338	222663998	222664148
ENSE00002264105	222659906	222660006
ENSE00002276969	222654243	222654298
ENSE00002281874	222648829	222648850
ENSE00002282876	222658722	222658823
ENSE00002283359	222654389	222654479
ENSE00002320982	222654655	222654793
ENSE00003465133	222650793	222650903
ENSE00003506034	222651977	222652048
ENSE00003529400	222659622	222659657
ENSE00003536912	222659734	222659801
ENSE00003567647	222662056	222662124
ENSE00003575497	222660177	222660314
ENSE00003589906	222650634	222650711
ENSE00003592244	222650292	222650380
ENSE00003606455	222621159	222621292
ENSE00003608249	222645554	222645685
ENSE00003622767	222659453	222659513
ENSE00003645538	222627575	222630389
ENSE00003646611	222662253	222662332
ENSE00003647067	222632165	222632326
ENSE00003655443	222633104	222633249
ENSE00003674386	222624768	222624854

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.7627 / max 904.2777, expressed in 1822 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8714	37.8992	1820
8716	10.5497	1772
8717	1.0811	618
8718	0.4579	144
8715	0.3987	151
8713	0.1198	51
8712	0.0865	44
8711	0.0633	39
8710	0.0360	9
8720	0.0360	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.56	gold quality
adrenal tissue	UBERON:0018303	97.32	gold quality
body of pancreas	UBERON:0001150	97.27	gold quality
stromal cell of endometrium	CL:0002255	97.16	gold quality
mucosa of stomach	UBERON:0001199	97.01	gold quality
minor salivary gland	UBERON:0001830	96.79	gold quality
right lobe of liver	UBERON:0001114	96.60	gold quality
rectum	UBERON:0001052	96.40	gold quality
body of uterus	UBERON:0009853	96.38	gold quality
endocervix	UBERON:0000458	96.35	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.30	gold quality
left coronary artery	UBERON:0001626	96.28	gold quality
body of stomach	UBERON:0001161	96.26	gold quality
right ovary	UBERON:0002118	96.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.18	gold quality
gall bladder	UBERON:0002110	96.09	gold quality
right lobe of thyroid gland	UBERON:0001119	96.03	gold quality
right coronary artery	UBERON:0001625	96.01	gold quality
cerebellar hemisphere	UBERON:0002245	95.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.92	gold quality
lower esophagus	UBERON:0013473	95.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.88	gold quality
left ovary	UBERON:0002119	95.87	gold quality
cerebellar cortex	UBERON:0002129	95.82	gold quality
right lung	UBERON:0002167	95.81	gold quality
left lobe of thyroid gland	UBERON:0001120	95.76	gold quality
ascending aorta	UBERON:0001496	95.73	gold quality
thoracic aorta	UBERON:0001515	95.73	gold quality
tibial nerve	UBERON:0001323	95.64	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ADTRP, AKT1, PIK3R3

miRNA regulators (miRDB)

128 targeting MIA3, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 22)

• TANGO transfected cell lines revealed that TANGO expression reduces motility, whereas reduction of TANGO enhances migration. (PMID:17044017)
• The results from this study present TANGO as a novel ligand for CD11c, regulating migratory processes of hematopoietic cells. (PMID:17726152)
• Reduced expression of TANGO is associated with colon and hepatocellular carcinomas (PMID:17786351)
• genetic polymorphism is associated with an increased risk of myocardial infarction (PMID:21264445)
• results suggest a potential association of the MIA3 rs17465637 with cardiovascular disease in dyslipidemic patients with rheumatoid arthritis (PMID:22577832)
• We conclude that SNP rs17465637 in MIA3 is indeed a genetic risk factor for CAD across different ethnic populations including Han Chinese. (PMID:24125424)
• TANGO expression was strongly associated with tumour progression, nodal metastasis, clinical stage and number of blood or lymph vessels in oral squamous cell carcinoma. (PMID:24889917)
• TANGO1 is thus pivotal in concentrating procollagen VII in the lumen and recruiting ERGIC membranes on the cytoplasmic surface of the endoplasmic reticulum. (PMID:26568311)
• TANGO1/CTAGE5 receptor serves as a polyvalent template for assembly of large COPII coats. (PMID:27551091)
• ADTRP positively regulates PIK3R3 expression, which leads to activation of AKT and up-regulation of MIA3/TANGO1, thereby regulating endothelial cell functions directly relevant to atherosclerosis. (PMID:28341552)
• Mammalian endoplasmic reticulum exit sites are organized by TANGO1 acting as a scaffold, in cooperation with Sec16 for efficient secretion. (PMID:28442536)
• These data showed that the NRZ tether is required for TANGO1 to assemble into a ring and indicated that stable complexes of TANGO1, cTAGE5 and TANGO1-short, recruit the tether. (PMID:29513218)
• Both cTAGE5 and SEC12 were exported with TANGO1 in large COPII carriers. (PMID:30545919)
• The Mediterranean diet reduces the genetic risk of chromosome 9p21 for myocardial infarction in an Asian population community cohort. (PMID:31804579)
• Biallelic TANGO1 mutations cause a novel syndromal disease due to hampered cellular collagen secretion. (PMID:32101163)
• TANGO1 membrane helices create a lipid diffusion barrier at curved membranes. (PMID:32452385)
• Low HDL concentration in rs2048327-G carriers can predispose men to develop coronary heart disease: Tehran Cardiometabolic genetic study (TCGS). (PMID:33581269)
• A general role for TANGO1, encoded by MIA3, in secretory pathway organization and function. (PMID:34350936)
• A novel mutation in collagen transport protein, MIA3 gene, detected in a patient with clinical symptoms of Ehlers-Danlos hypermobile syndrome. (PMID:36603143)
• Caspase 1 Enhances Transport and Golgi Organization Protein 1 Expression to Promote Procollagen Export From the Endoplasmic Reticulum in Systemic Sclerosis Contributing to Fibrosis. (PMID:37067501)
• TANGO1 interacts with NRTN to promote hepatocellular carcinoma progression by regulating the PI3K/AKT/mTOR signaling pathway. (PMID:37211171)
• MIA3 promotes the degradation of GSH (glutathione) by binding to CHAC1, thereby promoting the progression of hepatocellular carcinoma. (PMID:37948019)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mia3	ENSMUSG00000056050
rattus_norvegicus	Mia3	ENSRNOG00000059202
drosophila_melanogaster	Tango1	FBGN0286898

Paralogs (10): OTOR (ENSG00000125879), MIA2 (ENSG00000150527), SPZ1 (ENSG00000164299), CTAGE1 (ENSG00000212710), CTAGE9 (ENSG00000236761), MIA (ENSG00000261857), CTAGE15 (ENSG00000271079), CTAGE6 (ENSG00000271321), CTAGE4 (ENSG00000288784), CTAGE8 (ENSG00000289604)

Protein

Protein identifiers

Transport and Golgi organization protein 1 homolog — Q5JRA6 (reviewed: Q5JRA6)

Alternative names: C219-reactive peptide, D320, Melanoma inhibitory activity protein 3

All UniProt accessions (2): Q5JRA6, A0A0A0MRH6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum. This protein is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers. It may participate in cargo loading of COL7A1 at endoplasmic reticulum exit sites by binding to COPII coat subunits Sec23/24 and guiding SH3-bound COL7A1 into a growing carrier. Does not play a role in global protein secretion and is apparently specific to COL7A1 cargo loading. However, it may participate in secretion of other proteins in cells that do not secrete COL7A1. It is also specifically required for the secretion of lipoproteins by participating in their export from the endoplasmic reticulum. Required for correct assembly of COPII coat components at endoplasmic reticulum exit sites (ERES) and for the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES.

Subunit / interactions. Interacts with MIA2. Interacts (via SH3 domain) with COL7A1. Interacts with the COPII coat subunits SEC23A, SEC23B and maybe SEC24C. May interact with APOB and MIA2. Isoform 1 and isoform 4 interact with SEC16A.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Broadly expressed, except in bone marrow and peripheral blood mononuclear cells. Down-regulated in melanoma tissue.

Disease relevance. Odontochondrodysplasia 2 with hearing loss and diabetes (ODCD2) [MIM:619269] An autosomal recessive disorder characterized by dentinogenesis imperfecta, delayed tooth eruption, growth retardation with proportionate short stature, skeletal abnormalities, and dysmorphic facies in association with insulin-dependent diabetes mellitus, sensorineural hearing loss, and mild intellectual disability. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The proline-rich domain (PRD) contains repeated PPP motifs. A single PPP motif is necessary and sufficient to mediate interaction with the COPII coat subunits SEC23A and SEC23B. Although 2 transmembrane domains are predicted, PubMed:19269366 showed that it only contains one transmembrane domain. The other predicted transmembrane region is probably a hairpin-type region embedded into the membrane, which does not cross the membrane. It is unclear which of the 2 predicted transmembrane regions is the transmembrane or the hairpin-type region.

Similarity. Belongs to the MIA/OTOR family. Tango1 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5JRA6-1	1, TANGO1L	yes
Q5JRA6-2	2
Q5JRA6-3	3
Q5JRA6-4	4, TANGO1S

RefSeq proteins (6): NP_001287796, NP_001310991, NP_001310992, NP_001310993, NP_001310994, NP_940953* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR051500	cTAGE_MIA/OTOR	Family

Pfam: PF07653

UniProt features (88 total): compositionally biased region 26, modified residue 15, region of interest 10, strand 8, splice variant 5, sequence variant 5, sequence conflict 4, coiled-coil region 3, topological domain 3, glycosylation site 2, signal peptide 1, chain 1, intramembrane region 1, transmembrane region 1, domain 1, helix 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5KYN	X-RAY DIFFRACTION	2.55
5KYW	X-RAY DIFFRACTION	3.2
5KYU	X-RAY DIFFRACTION	3.51
7R3M	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JRA6-F1	52.49	0.18

Functional residue map

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

Post-translational modifications (15): 226, 229, 727, 876, 1067, 1431, 1666, 1678, 1706, 1727, 1741, 1745, 1784, 1892, 1906

Glycosylation sites (2): 246, 589

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-5694530	Cargo concentration in the ER
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 355 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_VESICLE_ORGANIZATION, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_VESICLE_MEDIATED_TRANSPORT, SCIBETTA_KDM5B_TARGETS_UP, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_MONONUCLEAR_CELL_MIGRATION, GOBP_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_WOUND_HEALING, GOBP_CELL_CELL_ADHESION, GOBP_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_LEUKOCYTE_MIGRATION

GO Biological Process (19): cell migration involved in sprouting angiogenesis (GO:0002042), positive regulation of leukocyte migration (GO:0002687), exocytosis (GO:0006887), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), endoplasmic reticulum organization (GO:0007029), negative regulation of cell adhesion (GO:0007162), protein secretion (GO:0009306), protein transport (GO:0015031), negative regulation of cell migration (GO:0030336), vesicle cargo loading (GO:0035459), wound healing (GO:0042060), lipoprotein transport (GO:0042953), protein localization to endoplasmic reticulum exit site (GO:0070973), COPII-coated vesicle cargo loading (GO:0090110), cellular response to oxidised low-density lipoprotein particle stimulus (GO:0140052), negative regulation of leukocyte cell-cell adhesion (GO:1903038), negative regulation of lymphocyte migration (GO:2000402), vesicle-mediated transport (GO:0016192), system development (GO:0048731)

GO Molecular Function (2): cargo receptor activity (GO:0038024), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum exit site (GO:0070971), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Metabolism of proteins	2
Post-translational protein modification	2
ER to Golgi Anterograde Transport	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle-mediated transport	3
transport	3
secretion by cell	2
cytoplasm	2
intracellular transport	2
protein transport	2
endoplasmic reticulum	2
cellular anatomical structure	2
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
positive regulation of immune system process	1
regulation of leukocyte migration	1
positive regulation of cell migration	1
leukocyte migration	1
vesicle fusion to plasma membrane	1
intercellular transport	1
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
intracellular protein localization	1
establishment of protein localization	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
response to wounding	1
tissue regeneration	1
lipoprotein localization	1
protein localization to endoplasmic reticulum	1
vesicle cargo loading	1
COPII-coated vesicle budding	1
cellular response to low-density lipoprotein particle stimulus	1
leukocyte cell-cell adhesion	1
negative regulation of cell-cell adhesion	1
regulation of leukocyte cell-cell adhesion	1
negative regulation of mononuclear cell migration	1

Protein interactions and networks

STRING

2095 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIA3	SEC24B	O95487	971
MIA3	MIA2	Q96PC5	947
MIA3	TRAPPC2	P0DI81	857
MIA3	SEC24A	O95486	835
MIA3	SEC23A	Q15436	827
MIA3	SEC16A	O15027	795
MIA3	PREB	Q9HCU5	785
MIA3	COL7A1	Q02388	744
MIA3	SCFD1	Q8WVM8	718
MIA3	SERPINH1	P29043	712
MIA3	SEC13	P55735	709
MIA3	GOLGA2	Q08379	638
MIA3	LMAN1	P49257	631
MIA3	KLHL12	Q53G59	624
MIA3	SAR1B	Q9Y6B6	613

IntAct

149 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MARCHF5	MFN2	psi-mi:“MI:0914”(association)	0.670
MIA2	RGPD8	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
SAV1	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
MIA3	LENG8	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	MIA3	psi-mi:“MI:0915”(physical association)	0.560
CLIC3	MIA3	psi-mi:“MI:0915”(physical association)	0.560
NCK2	MIA3	psi-mi:“MI:0915”(physical association)	0.560
MIA3	HOMER3	psi-mi:“MI:0915”(physical association)	0.560
SERPINA10	MIA3	psi-mi:“MI:0915”(physical association)	0.560
CLTB	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
SERPINA5	ZZEF1	psi-mi:“MI:0914”(association)	0.530
HAO2	EIF4G3	psi-mi:“MI:0914”(association)	0.530
SERPINA12	TSPAN6	psi-mi:“MI:0914”(association)	0.530
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
PPFIBP2	SNAP29	psi-mi:“MI:0914”(association)	0.530
ANO6	CDC27	psi-mi:“MI:0914”(association)	0.530
ANO4	ANO6	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530

BioGRID (317): MIA3 (Two-hybrid), MIA3 (Two-hybrid), MIA3 (Two-hybrid), MIA3 (Two-hybrid), MIA3 (Affinity Capture-MS), MIA3 (Affinity Capture-MS), MIA3 (Affinity Capture-MS), MIA3 (Affinity Capture-MS), MIA3 (Affinity Capture-MS), MIA3 (Affinity Capture-MS), MIA3 (Affinity Capture-MS), MIA3 (Affinity Capture-MS), CRTAP (Affinity Capture-MS), SIGLEC12 (Affinity Capture-MS), CTAGE5 (Affinity Capture-MS)

ESM2 similar proteins: A2TJV2, A4FU49, A5YM69, A6QP92, E9Q0C6, E9Q3S4, E9Q7D5, O94854, P20398, P43597, Q00756, Q08DY0, Q0VC16, Q12802, Q32L62, Q5JRA6, Q5QJ38, Q5TM68, Q5VWK0, Q68DN1, Q68DQ2, Q69ZZ9, Q6AZ54, Q6P6B1, Q7TSG5, Q810T2, Q86TB3, Q8BHW6, Q8BI84, Q8K0S2, Q8K4E0, Q8N3K9, Q8NDH2, Q8TCU4, Q8VBT6, Q91ZB0, Q923B3, Q924C5, Q95J40, Q95JY5

Diamond homologs: Q0VC16, Q16674, Q28038, Q5JRA6, Q61865, Q62946, Q8BI84, Q9I8P5, Q9I8P6, Q9JIE3, Q9NRC9, P52735, Q60992, Q96PC5, Q9R0C8, Q9UKW4, Q91ZV0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	260
Likely benign	36
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1064426	NM_198551.4(MIA3):c.3621A>G (p.Arg1207=)	Pathogenic
4076961	NM_198551.4(MIA3):c.354+2T>G	Likely pathogenic
4277882	NM_198551.4(MIA3):c.3720+1G>A	Likely pathogenic

SpliceAI

3629 predictions. Top by Δscore:

Variant	Effect	Δscore
1:222618239:CAGCA:C	donor_gain	1.0000
1:222618240:AGCA:A	donor_gain	1.0000
1:222618241:GCA:G	donor_gain	1.0000
1:222618241:GCAG:G	donor_gain	1.0000
1:222618242:CA:C	donor_gain	1.0000
1:222618242:CAG:C	donor_loss	1.0000
1:222618244:G:T	donor_loss	1.0000
1:222618244:GTGA:G	donor_gain	1.0000
1:222618248:G:GG	donor_gain	1.0000
1:222619069:G:GT	donor_gain	1.0000
1:222621151:A:AG	acceptor_gain	1.0000
1:222621152:T:G	acceptor_gain	1.0000
1:222621153:A:AG	acceptor_gain	1.0000
1:222621154:T:G	acceptor_gain	1.0000
1:222621155:A:AG	acceptor_gain	1.0000
1:222621155:ACAGT:A	acceptor_gain	1.0000
1:222621156:C:G	acceptor_gain	1.0000
1:222621157:A:AG	acceptor_gain	1.0000
1:222621157:A:G	acceptor_loss	1.0000
1:222621157:AGT:A	acceptor_gain	1.0000
1:222621158:G:GT	acceptor_gain	1.0000
1:222621158:GT:G	acceptor_gain	1.0000
1:222621158:GTG:G	acceptor_gain	1.0000
1:222621158:GTGT:G	acceptor_gain	1.0000
1:222621158:GTGTT:G	acceptor_gain	1.0000
1:222621288:G:GT	donor_gain	1.0000
1:222621288:GAAGT:G	donor_gain	1.0000
1:222621289:AAGT:A	donor_gain	1.0000
1:222621289:AAGTG:A	donor_loss	1.0000
1:222621290:AGT:A	donor_gain	1.0000

AlphaMissense

12638 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:222652249:G:C	A1335P	0.998
1:222659657:G:C	W1602C	0.997
1:222659657:G:T	W1602C	0.997
1:222659749:G:C	A1608P	0.997
1:222659655:T:A	W1602R	0.996
1:222659655:T:C	W1602R	0.996
1:222654754:T:C	L1523P	0.994
1:222658748:G:C	R1545P	0.994
1:222659740:G:C	A1605P	0.994
1:222658727:T:C	L1538P	0.993
1:222618237:T:A	C43S	0.992
1:222618237:T:C	C43R	0.992
1:222618238:G:C	C43S	0.992
1:222652241:T:C	L1332P	0.992
1:222618222:T:A	C38S	0.991
1:222618223:G:C	C38S	0.991
1:222652313:T:C	L1356P	0.991
1:222654763:T:C	L1526P	0.991
1:222659643:G:C	A1598P	0.991
1:222659735:T:C	L1603P	0.991
1:222659744:G:C	R1606P	0.991
1:222621212:T:C	F63L	0.990
1:222621214:T:A	F63L	0.990
1:222621214:T:G	F63L	0.990
1:222659512:A:C	Q1590P	0.990
1:222621246:T:A	V74D	0.989
1:222654783:G:C	A1533P	0.989
1:222659654:C:A	N1601K	0.989
1:222659654:C:G	N1601K	0.989
1:222659782:G:C	A1619P	0.988

dbSNP variants (sampled 300 via entrez): RS1000124225 (1:222622415 A>C), RS1000134295 (1:222652639 A>C), RS1000174285 (1:222650166 T>C,G), RS1000232738 (1:222657637 G>C,T), RS1000546349 (1:222659037 G>A), RS1000552384 (1:222659168 G>A,C), RS1000569632 (1:222630688 G>A), RS1000606129 (1:222658883 A>G), RS1000677677 (1:222644746 G>T), RS1000759816 (1:222644899 G>A), RS1000828485 (1:222664672 G>A), RS1000860608 (1:222650482 ATT>A), RS1000876740 (1:222617788 A>G), RS1000880634 (1:222664943 C>T), RS1000899182 (1:222625111 G>A)

Disease associations

OMIM: gene MIM:613455 | disease phenotypes: MIM:619269

GenCC curated gene-disease

Disease	Classification	Inheritance
odontochondrodysplasia 2 with hearing loss and diabetes	Strong	Autosomal recessive

Mondo (2): coronary artery disorder (MONDO:0005010), odontochondrodysplasia 2 with hearing loss and diabetes (MONDO:0031010)

Orphanet (0):

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000126	Hydronephrosis
HP:0000278	Retrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000488	Retinopathy
HP:0000696	Delayed eruption of permanent teeth
HP:0000703	Dentinogenesis imperfecta
HP:0000704	Periodontitis
HP:0000826	Precocious puberty
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0000989	Pruritus
HP:0001256	Mild intellectual disability
HP:0001510	Growth delay
HP:0001513	Obesity
HP:0001831	Short toe
HP:0002099	Asthma
HP:0002650	Scoliosis
HP:0003508	Proportionate short stature
HP:0003593	Infantile onset
HP:0004209	Clinodactyly of the 5th finger
HP:0006480	Premature loss of teeth
HP:0009803	Short phalanx of finger
HP:0010230	Cone-shaped epiphyses of the phalanges of the hand
HP:0012594	Moderate albuminuria
HP:0030866	Large knee
HP:0100651	Type I diabetes mellitus

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000057_6	Coronary heart disease	1.000000e-06
GCST000340_8	Myocardial infarction (early onset)	1.000000e-09
GCST000998_2	Coronary heart disease	1.000000e-08
GCST003116_21	Coronary artery disease	1.000000e-12
GCST003117_23	Myocardial infarction	2.000000e-11
GCST004787_18	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	9.000000e-14
GCST005194_20	Coronary artery disease	9.000000e-28
GCST005195_145	Coronary artery disease	6.000000e-28
GCST005196_194	Coronary artery disease	8.000000e-31
GCST010479_54	Coronary artery disease	6.000000e-12
GCST010480_1	Coronary artery disease	3.000000e-10
GCST010866_28	Coronary artery disease	5.000000e-48
GCST010867_51	Coronary artery disease	1.000000e-22
GCST011364_3	Myocardial infarction	3.000000e-15
GCST011365_32	Myocardial infarction	2.000000e-24

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003324	Coronary Artery Disease	C14.280.647.250.260; C14.907.137.126.339; C14.907.585.250.260

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066483 (SINGLE PROTEIN)

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

PharmGKB variants

12 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs904323	MIA3		0.00	0
rs1053316	MIA3		0.00	0
rs2088514	MIA3		0.00	0
rs2291834	MIA3		0.00	0
rs3002145	MIA3		0.00	0
rs3008610	MIA3		0.00	0
rs10495197	MIA3		0.00	0
rs17163303	MIA3		0.00	0
rs35397194	MIA3		0.00	0
rs35822937	MIA3		0.00	0
rs75328711	MIA3		0.00	0
rs142155704	MIA3		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.49	Kd	3222	nM	CHEMBL3752910
5.44	ED50	3637	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148749: Binding affinity to human MIA3 incubated for 45 mins by Kinobead based pull down assay	kd	3.2216	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects methylation, increases expression	4
sodium arsenite	increases expression, decreases expression	4
Valproic Acid	increases expression	3
Cyclosporine	increases expression	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression	2
Endosulfan	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	decreases expression	1
butyraldehyde	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	decreases expression, increases abundance, affects cotreatment	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651791	Binding	Binding affinity to human MIA3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2C7	HAP1 MIA3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00025766	PHASE4	COMPLETED	Angioplasty and Heart Stents to Treat Individuals With an Occluded Artery Following a Heart Attack
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00111566	PHASE4	COMPLETED	BRIEF-PCI: Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention
NCT00129038	PHASE4	COMPLETED	Modified-release Dipyridamole/Aspirin (200mg/25mg bd) Versus Aspirin (75mg) in Aspirin-resistant Patients
NCT00133003	PHASE4	COMPLETED	Abciximab, Clopidogrel and Percutaneous Coronary Intervention in Acute Coronary Syndrome (ISAR-REACT-2)
NCT00133237	PHASE4	COMPLETED	Drug-eluting-stents for Unprotected Left Main Stem Disease (ISAR-LEFT-MAIN)
NCT00133692	PHASE4	COMPLETED	INVEST: INternational VErapamil SR Trandolapril STudy
NCT00139386	PHASE4	COMPLETED	Candesartan for Prevention of Cardiovascular Events After Cypher or Taxus Coronary Stenting (4C) Trial
NCT00140465	PHASE4	COMPLETED	75 or 150 mg Clopidogrel Maintenance Doses Following PCI (ISAR-CHOICE-2)
NCT00140530	PHASE4	COMPLETED	Nonpolymer- and Polymer-Based Drug-Eluting Stents for Restenosis (ISAR-TEST-1)
NCT00146575	PHASE4	COMPLETED	Sirolimus- and Paclitaxel-Eluting Stents for Small Vessels (ISAR-SMART-3)
NCT00152308	PHASE4	TERMINATED	Non-Polymer-Based, Rapamycin-Eluting Stents to Prevent Restenosis
NCT00155350	PHASE4	UNKNOWN	Treatment of Coronary Atherosclerosis by Insulin Sensitizers in Insulin-Resistant Patients
NCT00162370	PHASE4	COMPLETED	A Study of Stress Echocardiography in Post-Menopausal Women at Risk for Coronary Disease
NCT00163202	PHASE4	COMPLETED	Comparative Atorvastatin Pleiotropic Effects
NCT00169819	PHASE4	COMPLETED	EArly Discharge After Transradial Stenting of CoronarY Arteries: The EASY Study
NCT00171275	PHASE4	COMPLETED	Fluvastatin in the Therapy of Acute Coronary Syndrome
NCT00175240	PHASE4	COMPLETED	Enhancing the Secondary Prevention of Coronary Artery Disease
NCT00180388	PHASE4	TERMINATED	VENEK: Healing in Different Vein Harvesting Methods During Aortocoronary Coronary Artery Bypass Graft Surgery (CABG)
NCT00180583	PHASE4	COMPLETED	Vision II: Evaluation of GALILEO Intravascular Radiotherapy System
NCT00189215	PHASE4	COMPLETED	Long-Term Cognitive Decline After Coronary Artery Bypass Grafting: is Off-Pump Surgery Beneficial?
NCT00200629	PHASE4	TERMINATED	Both Exercise and Adenosine Stress Testing
NCT00202904	PHASE4	COMPLETED	Effectiveness and Safety of Ezetimibe Added to Atorvastatin in Patients With High Cholesterol and Coronary Heart Disease (Study P03740)
NCT00209404	PHASE4	COMPLETED	Iodixanol in Multidetector-Row Computed Tomography-Coronary Angiography (MDCT-CA)
NCT00209430	PHASE4	COMPLETED	Renal Effects of Two Iodinated Contrast Media in Patients at Risk Undergoing Coronary Angiography
NCT00220558	PHASE4	UNKNOWN	GISSOC II: Sirolimus Eluting Stent Versus Bare Metal Stent in Chronic Total Coronary Occlusions
NCT00222261	PHASE4	COMPLETED	Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.
NCT00229528	PHASE4	COMPLETED	Effect of Paroxetine on COAT-Platelet Production in Normal Volunteers and Patients With Cardiovascular Disease
NCT00232804	PHASE4	COMPLETED	The BRIDGE Registry: Safety and Efficacy Registry of Bx Cypher Stent
NCT00232856	PHASE4	COMPLETED	A Study of the Cypher SES to Treat Restenotic Native Coronary Artery Lesions.
NCT00235066	PHASE4	COMPLETED	The CYPHER™ Stent Study in Patients With Small de Novo Coronary Artery Lesions.
NCT00235092	PHASE4	COMPLETED	The REALITY Study - Head-to-Head Comparison Between Cypher and Taxus
NCT00235950	PHASE4	COMPLETED	Assessment of the Lipid Lowering Effect of Rosuvastatin Compared to Atorvastatin in Subjects With Coronary Heart Disease
NCT00238004	PHASE4	UNKNOWN	The Low HDL On Six Weeks Statin Therapy (LOW) Study
NCT00241904	PHASE4	COMPLETED	Reducing Total Cardiovascular Risk in an Urban Community
NCT00242944	PHASE4	COMPLETED	Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS)
NCT00243477	PHASE4	COMPLETED	MOTIV Study- Effect of Antidepressive Treatment by Escitalopram in Patients Undergoing Coronary Artery Bypass Grafting
NCT00244530	PHASE4	COMPLETED	Prophylactic Effect of Nifedipine on Further Decline in Renal Function in Patients Undergoing Open-Heart Surgery
NCT00245401	PHASE4	COMPLETED	CYPHERTM Stent Post-Marketing Surveillance Registry (US-PMS)