BOLA3

bolA family member 3, the group of Mitochondrial iron-sulfur assembly components

Basic information

Region (hg38): 2:74135400-74147912

Links

ENSG00000163170 ∙ NCBI:388962 ∙ OMIM:613183 ∙ HGNC:24415 ∙ Uniprot:Q53S33 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple mitochondrial dysfunctions syndrome 2 (Strong), mode of inheritance: AR
• multiple mitochondrial dysfunctions syndrome 2 (Strong), mode of inheritance: AR
• multiple mitochondrial dysfunctions syndrome 2 (Strong), mode of inheritance: AR
• multiple mitochondrial dysfunctions syndrome 2 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple mitochondrial dysfunctions syndrome 2 with hyperglycinemia	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Neurologic	11156534; 21944046; 22562699; 24334290

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BOLA3 gene.

• Multiple mitochondrial dysfunctions syndrome 2 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BOLA3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	4		5
missense		2	32	2		36
nonsense	1					1
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			2	1		3
non coding			4	14	14	32
Total	1	3	39	20	14

Highest pathogenic variant AF is 0.0000460

Variants in BOLA3

This is a list of pathogenic ClinVar variants found in the BOLA3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-74135403-C-T		Multiple mitochondrial dysfunctions syndrome 2	Uncertain significance (Jan 12, 2018)
2-74135459-A-G		Multiple mitochondrial dysfunctions syndrome 2	Uncertain significance (Jan 12, 2018)
2-74135562-A-G		Multiple mitochondrial dysfunctions syndrome 2	Uncertain significance (Jan 13, 2018)
2-74135597-C-T		Inborn genetic diseases	Uncertain significance (Apr 20, 2022)
2-74135598-G-A		Multiple mitochondrial dysfunctions syndrome 2 • BOLA3-related disorder	Conflicting classifications of pathogenicity (Dec 31, 2023)
2-74135600-T-C		Multiple mitochondrial dysfunctions syndrome 2	Uncertain significance (Mar 12, 2019)
2-74135605-G-A			Likely benign (Jun 09, 2023)
2-74135607-CAG-C		Multiple mitochondrial dysfunctions syndrome 2	Uncertain significance (Feb 01, 2021)
2-74135611-G-A			Likely benign (Jul 12, 2023)
2-74135619-T-C		Inborn genetic diseases	Uncertain significance (Aug 09, 2022)
2-74135621-C-T		Inborn genetic diseases • Multiple mitochondrial dysfunctions syndrome 2	Uncertain significance (Dec 19, 2022)
2-74135622-G-A		Multiple mitochondrial dysfunctions syndrome 2	Uncertain significance (-)
2-74135634-T-C		Inborn genetic diseases	Uncertain significance (Aug 22, 2022)
2-74135649-C-T			Uncertain significance (Nov 01, 2022)
2-74135659-C-G		Multiple mitochondrial dysfunctions syndrome 2	Likely pathogenic (Jul 11, 2023)
2-74135676-A-C		not specified	Benign (Jan 22, 2024)
2-74135677-T-A			Likely benign (Jul 10, 2023)
2-74135863-T-A			Benign (Jun 14, 2018)
2-74135948-CT-C			Benign (Aug 06, 2019)
2-74135948-C-CT			Benign (Aug 13, 2019)
2-74135948-C-CTT			Benign (Aug 18, 2019)
2-74135948-C-CTTT			Likely benign (Aug 11, 2019)
2-74135957-T-G			Benign (Oct 21, 2019)
2-74142024-A-T			Benign (Jun 14, 2018)
2-74142263-T-G		not specified • Multiple mitochondrial dysfunctions syndrome 2	Conflicting classifications of pathogenicity (Dec 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BOLA3	protein_coding	protein_coding	ENST00000327428	4	12597

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.149	0.784	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.547	48	59.9	0.801	0.00000327	689
Missense in Polyphen		11	16.552	0.66456		206
Synonymous	0.542	16	19.0	0.842	9.24e-7	201
Loss of Function	1.50	2	5.93	0.337	3.52e-7	66

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000967	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a mitochondrial iron-sulfur (Fe-S) cluster assembly factor that facilitates (Fe-S) cluster insertion into a subset of mitochondrial proteins. Probably acts together with NFU1 (PubMed:27532772). {ECO:0000250|UniProtKB:P39724, ECO:0000305|PubMed:27532772}.

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.269
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.264
• hipred: N
• hipred_score: 0.285
• ghis: 0.648

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bola3

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;biological_process
• Cellular component: mitochondrion
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;molecular_function