MIA3

MIA SH3 domain ER export factor 3, the group of MIA family|CTAGE family

Basic information

Region (hg38): 1:222618097-222668007

Links

ENSG00000154305 ∙ NCBI:375056 ∙ OMIM:613455 ∙ HGNC:24008 ∙ Uniprot:Q5JRA6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• odontochondrodysplasia 2 with hearing loss and diabetes (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ondontochondrodysplasia 2 with hearing loss and diabetes	AR	Audiologic/Otolaryngologic; Endocrine	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition can involved insulin-dependent diabetes mellitus, and awareness may enable early medical management	Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic	32101163

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MIA3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MIA3 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		2
missense			106	11	1	118
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding					1	1
Total	0	0	106	13	2

Variants in MIA3

This is a list of pathogenic ClinVar variants found in the MIA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-222618154-G-A		Inborn genetic diseases	Uncertain significance (May 10, 2023)
1-222624769-T-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
1-222624774-C-T		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
1-222624816-C-T		Inborn genetic diseases	Uncertain significance (Apr 01, 2024)
1-222624820-A-C		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
1-222627641-T-G		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
1-222627645-G-A		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
1-222627756-C-T		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
1-222627760-A-C		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)
1-222627890-C-G		Inborn genetic diseases	Uncertain significance (Oct 24, 2023)
1-222627891-A-C		Inborn genetic diseases	Uncertain significance (Oct 24, 2023)
1-222627893-G-C			Likely benign (Jan 01, 2024)
1-222628013-A-G		Inborn genetic diseases	Uncertain significance (Jun 10, 2024)
1-222628067-G-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
1-222628106-G-A		Inborn genetic diseases	Likely benign (Jul 28, 2021)
1-222628129-T-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
1-222628235-A-G		Inborn genetic diseases	Likely benign (Jul 20, 2021)
1-222628301-G-A		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
1-222628307-A-G		Inborn genetic diseases	Uncertain significance (May 20, 2024)
1-222628319-A-T			Benign (Jul 01, 2023)
1-222628410-C-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
1-222628459-A-T		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
1-222628501-A-T		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
1-222628530-C-T		Inborn genetic diseases	Uncertain significance (May 24, 2023)
1-222628548-G-C		Inborn genetic diseases	Uncertain significance (Jul 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MIA3	protein_coding	protein_coding	ENST00000344922	28	49927

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0367	0.963	124782	0	71	124853	0.000284

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.694	927	988	0.938	0.0000500	12590
Missense in Polyphen		213	256.63	0.82998		3240
Synonymous	2.14	303	354	0.855	0.0000184	3548
Loss of Function	6.46	21	85.4	0.246	0.00000413	1144

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000397	0.000397
Ashkenazi Jewish	0.000604	0.000596
East Asian	0.000223	0.000222
Finnish	0.0000928	0.0000926
European (Non-Finnish)	0.000222	0.000221
Middle Eastern	0.000223	0.000222
South Asian	0.000671	0.000621
Other	0.000861	0.000824

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:27138255). {ECO:0000269|PubMed:19269366, ECO:0000269|PubMed:27138255}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Cargo concentration in the ER;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.0883

Intolerance Scores

• loftool: 0.545
• rvis_EVS: 0.79
• rvis_percentile_EVS: 87.34

Haploinsufficiency Scores

• pHI: 0.0661
• hipred: N
• hipred_score: 0.271
• ghis: 0.478

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.266

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mia3
• Phenotype: respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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); limbs/digits/tail phenotype; skeleton phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype

Gene ontology

• Biological process: cell migration involved in sprouting angiogenesis;positive regulation of leukocyte migration;exocytosis;endoplasmic reticulum to Golgi vesicle-mediated transport;endoplasmic reticulum organization;negative regulation of cell adhesion;protein secretion;protein transport;negative regulation of cell migration;vesicle cargo loading;wound healing;lipoprotein transport;post-translational protein modification;cellular protein metabolic process;protein localization to endoplasmic reticulum exit site;COPII-coated vesicle cargo loading;cellular response to oxidised low-density lipoprotein particle stimulus;negative regulation of leukocyte cell-cell adhesion;negative regulation of lymphocyte migration
• Cellular component: Golgi membrane;endoplasmic reticulum lumen;endoplasmic reticulum membrane;membrane;integral component of membrane;intracellular membrane-bounded organelle;endoplasmic reticulum exit site
• Molecular function: protein binding;lipoprotein transporter activity