MIGA1

Chr 1

mitoguardin 1

Also known as: FAM73A

The protein regulates mitochondrial fusion by forming dimers at the mitochondrial outer membrane and facilitating PLD6/MitoPLD dimer formation, potentially through phospholipid metabolism regulation. Mutations cause autosomal recessive hypomyelinating leukodystrophy-15, characterized by developmental delay, intellectual disability, and progressive white matter abnormalities affecting the central nervous system. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.728).

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
15
P/LP submissions
0%
P/LP missense
0.73
LOEUF
GOF
Mechanism· predicted
Clinical SummaryMIGA1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 16 VUS of 45 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.73LOEUF
pLI 0.000
Z-score 2.82
OE 0.49 (0.330.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.53Z-score
OE missense 0.92 (0.831.01)
302 obs / 329.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.330.73)
00.351.4
Missense OE0.92 (0.831.01)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 17 / 35.0Missense obs/exp: 302 / 329.2Syn Z: 0.37
DN
0.6065th %ile
GOF
0.6639th %ile
LOF
0.4331th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

45 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic1
VUS16
14
Pathogenic
1
Likely Pathogenic
16
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
1
0
1
VUS
0
7
9
0
16
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0724031

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MIGA1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found