MIGA1

Chr 1

mitoguardin 1

Also known as: FAM73A

NCBI Gene: 374986 ENSG00000180488 UniProt: Q8NAN2

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).

ResearchSummary from RefSeq, UniProt

Enables protein heterodimerization activity and protein homodimerization activity. Involved in mitochondrial fusion. Located in mitochondrion and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.73

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.000

Z-score 2.82

OE 0.49 (0.33–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.53Z-score

OE missense 0.92 (0.83–1.01)

302 obs / 329.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.33–0.73)

0≤0.351.4

Missense OE?0.92 (0.83–1.01)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 17 / 35.0Missense obs/exp: 302 / 329.2Syn Z: 0.37

Background carrier burden — how many people carry a rare variant somewhere in MIGA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 81

829 rare PASS variants

Rare truncating (LoF)

1 in 440

146 rare PASS variants

Rare synonymous (reference)

1 in 150

279 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MIGA1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 470
South Asian	~43k	1 in 82	1 in 610
Remaining (unassigned)	~30k	1 in 67	1 in 570
European (Finnish)	~27k	1 in 160	1 in 3,300
Admixed American	~22k	1 in 86	1 in 680
African / African American	~21k	1 in 66	1 in 750
East Asian	~20k	1 in 86	1 in 600
Ashkenazi Jewish	~13k	1 in 600	none seen
Middle Eastern	~2,884	1 in 74	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 15 coding exons well covered in gnomAD exomes; exons 2, 4, 5, 7, 9 marginal. Genomes: all 15.? see exons ↓