MIA3

Chr 1AR

MIA SH3 domain ER export factor 3

Also known as: D320, ODCD2, TANGO, TANGO1, UNQ6077

This protein functions as a cargo receptor that loads large proteins like collagen VII and lipoproteins into transport vesicles for export from the endoplasmic reticulum. Biallelic mutations cause odontochondrodysplasia 2, a syndrome involving skeletal dysplasia, hearing loss, and diabetes mellitus. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.354) and follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.351 OMIM phenotype
Clinical SummaryMIA3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.35LOEUF
pLI 0.037
Z-score 6.46
OE 0.25 (0.170.35)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.69Z-score
OE missense 0.94 (0.890.99)
927 obs / 988.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.170.35)
00.351.4
Missense OE0.94 (0.890.99)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 21 / 85.4Missense obs/exp: 927 / 988.4Syn Z: 2.14
DN
0.6746th %ile
GOF
0.3491th %ile
LOF
0.3067th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MIA3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →