MIA3
protein-codingMIA SH3 domain ER export factor 3, the group of MIA family|CTAGE family
Gene summary
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. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: LiferaOmics
Genetic evidence – Published Published reports of biallelic MIA3 variants (PMID 32101163, 40119123, 33778321) describe odontochondrodysplasia type 2, characterized primarily by skeletal dysplasia, dentinogenesis imperfecta, hearing loss, short stature, and metabolic abnormalities. These phenotypes are distinct from the proposed MIA3-related neurodevelopmental disorder with muscular dystrophy (AR) and do not demonstrate a primary neurodevelopmental disorder with muscular dystrophy presentation consistent with our disease definition. Because the published cases represent a different clinical entity, they are not scorable for this specific GDR. Published genetic evidence total = 0 / 12 Genetic evidence – Our cases Family 1 – One proband. Case-level (biallelic predicted null in AR model; homozygous scored once; consanguinity −0.5 applied) = 1.0; segregation = 0 (affected brother untested; not scorable); case-control = 0; Family 1 total = 1.0. Our cases total = 1.0 / 12 Additional unpublished evidence (not scored) We are aware of two additional unrelated families with a similar phenotype characterized by neurodevelopmental impairment and muscular dystrophy features, each harboring homozygous predicted loss-of-function variants in MIA3. However, these families are currently unpublished, and detailed phenotypic and segregation data are not yet publicly available. In keeping with transparency and reproducibility standards, these cases were not included in the formal scoring. Total genetic evidence (published + our cases) 0 + 1.0 = 1.0 / 12 Experimental evidence – Published Current experimental data for MIA3 support its role in collagen secretion and skeletal/connective tissue biology associated with odontochondrodysplasia. There is presently no published experimental evidence linking MIA3 to a neurodevelopmental disorder with muscular dystrophy phenotype. Experimental evidence total = 0 / 6 Overall score Genetic evidence = 1.0 Experimental evidence = 0 Overall score = 1.0 / 18
Inheritance Pattern: AR
Disease ID:MONDO:0031010
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0031010
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal; Neurologic
Intervention: Audiologic/Otolaryngologic; Endocrine
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MIA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198551.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 12 | 15 | ||
| missense | 274 | 33 | 1 | 308 | ||
| nonsense | 3 | 3 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 3 | 5 | |||
| Total | 1 | 2 | 284 | 45 | 1 | 333 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_940953.2 | 28 | MANE Select | |
| Ensembl | ENSP00000340900.5 | 28 | MANE Select | |
| RefSeq | NP_001287796.1 | 23 | Standard | |
| RefSeq | NP_001310991.1 | 29 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein phosphorylation
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- cell migration involved in sprouting angiogenesis
- positive regulation of leukocyte migration
- exocytosis
- endoplasmic reticulum to Golgi vesicle-mediated transport
- endoplasmic reticulum organization
Molecular Function
- protein binding
- lipoprotein transporter activity
Cellular Component
- Golgi membrane
- endoplasmic reticulum lumen
- endoplasmic reticulum membrane
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000344922
- Coding exons
- 28
- Length
- 49927
- Individuals with no LoFs
- 124782
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 71
- Defined
- 124853
- p
- 0.000284
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.694 | 927 | 988 | 0.938 | 0.0000500 | 12590 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.00027 | 0.00023 | rare |
| Ashkenazi Jewish | 0.00060 | 0.00060 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.00022 | 0.00022 | rare |
| South Asian | 0.00067 | 0.00062 | rare |
| Other | 0.00086 | 0.00082 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.0883
Intolerance Scores
- LoFtool
- 0.545
- RVIS EVS
- 0.79
- RVIS percentile EVS
- 87.34
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- N
- Indispensability score
- 0.266
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |