BOLA3

Chr 2AR

bolA family member 3

Also known as: MMDS2

The protein is essential for iron-sulfur cluster production required for maturation of lipoate-containing 2-oxoacid dehydrogenases and assembly of mitochondrial respiratory chain complexes. Mutations cause multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia, inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects disrupting normal mitochondrial function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.061 OMIM phenotype
Clinical SummaryBOLA3
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
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ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 61 VUS of 130 total submissions
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GeneReview available — BOLA3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.149
Z-score 1.50
OE 0.34 (0.141.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.55Z-score
OE missense 0.80 (0.641.02)
48 obs / 59.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.141.06)
00.351.4
Missense OE0.80 (0.641.02)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 2 / 5.9Missense obs/exp: 48 / 59.9Syn Z: 0.54
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongBOLA3-related multiple mitochondrial dysfunctions syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.5464th %ile
LOF
0.3647th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

130 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic7
VUS61
Likely Benign29
Benign17
Conflicting4
11
Pathogenic
7
Likely Pathogenic
61
VUS
29
Likely Benign
17
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
9
0
11
Likely Pathogenic
1
4
2
0
7
VUS
2
48
8
3
61
Likely Benign
0
4
19
6
29
Benign
0
0
17
0
17
Conflicting
4
Total556559129

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

View in ClinVar →

Protein Context — Lollipop Plot

BOLA3 · 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 →