BOLA1

Summary

BOLA1 (bolA family member 1, HGNC:24263) is a protein-coding gene on chromosome 1q21.2, encoding BolA-like protein 1 (Q9Y3E2). Acts as a mitochondrial iron-sulfur (Fe-S) cluster assembly factor that facilitates (Fe-S) cluster insertion into a subset of mitochondrial proteins.

Predicted to be involved in cell redox homeostasis; intracellular iron ion homeostasis; and iron-sulfur cluster assembly. Located in mitochondrion. Part of iron-sulfur cluster assembly complex.

Source: NCBI Gene 51027 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_016074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24263
Approved symbol	BOLA1
Name	bolA family member 1
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	CGI-143
Ensembl gene	ENSG00000178096
Ensembl biotype	protein_coding
OMIM	613181
Entrez	51027

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000369150, ENST00000369152, ENST00000369153, ENST00000476344, ENST00000864769

RefSeq mRNA: 3 — MANE Select: NM_016074 NM_001321025, NM_001321026, NM_016074

CCDS: CCDS939

Canonical transcript exons

ENST00000369152 — 2 exons

Exon	Start	End
ENSE00001448918	149900010	149900795
ENSE00001826545	149899568	149899672

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 90.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0213 / max 128.8738, expressed in 1792 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5040	6.0492	1629
5037	4.9914	1270
5039	3.5953	1490
5041	1.9867	1010
5036	0.3986	172

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.98	gold quality
apex of heart	UBERON:0002098	90.63	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.90	gold quality
lower esophagus	UBERON:0013473	88.88	gold quality
right adrenal gland	UBERON:0001233	88.34	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.90	gold quality
right lobe of liver	UBERON:0001114	87.75	gold quality
right adrenal gland cortex	UBERON:0035827	87.44	gold quality
left adrenal gland	UBERON:0001234	86.86	gold quality
left adrenal gland cortex	UBERON:0035825	86.78	gold quality
prefrontal cortex	UBERON:0000451	86.69	gold quality
gastrocnemius	UBERON:0001388	86.65	gold quality
body of stomach	UBERON:0001161	86.45	gold quality
muscle of leg	UBERON:0001383	86.43	gold quality
right atrium auricular region	UBERON:0006631	86.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.17	gold quality
skin of abdomen	UBERON:0001416	86.14	gold quality
mucosa of transverse colon	UBERON:0004991	86.12	gold quality
left coronary artery	UBERON:0001626	86.04	gold quality
skin of leg	UBERON:0001511	85.88	gold quality
popliteal artery	UBERON:0002250	85.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.58	gold quality
tibial artery	UBERON:0007610	85.56	gold quality
right lobe of thyroid gland	UBERON:0001119	85.19	gold quality
body of pancreas	UBERON:0001150	85.08	gold quality
anterior cingulate cortex	UBERON:0009835	85.08	gold quality
right uterine tube	UBERON:0001302	85.02	gold quality
descending thoracic aorta	UBERON:0002345	84.99	gold quality
aorta	UBERON:0000947	84.95	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.84
E-GEOD-110499	no	142.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting BOLA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-6886-3P	96.96	66.36	844
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-5739	88.09	63.94	123

Literature-anchored findings (GeneRIF, showing 4)

• BOLA-like proteins are widely conserved from prokaryotes to eukaryotes and may be involved in cell proliferation or cell-cycle regulation. (PMID:14718656)
• This study reported that all three human BolA proteins (hBolA1, hBolA2, and hBolA3) are novel non-classical secreted proteins identified with bioinformatics and molecular biology experiments. (PMID:18548201)
• is an aerobic, mitochondrial protein that prevents mitochondrial morphology aberrations induced by GSH depletion and reduces the associated oxidative shift of the mitochondrial thiol redox potential (PMID:22746225)
• Cluster exchange reactivity of [2Fe-2S]-bridged heterodimeric BOLA1-GLRX5. (PMID:32542995)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bola1	ENSDARG00000039915
mus_musculus	Bola1	ENSMUSG00000015943
rattus_norvegicus	Bola1	ENSRNOG00000021185
drosophila_melanogaster	CG31126	FBGN0051126
caenorhabditis_elegans		WBGENE00019658

Paralogs (3): BOLA3 (ENSG00000163170), BOLA2B (ENSG00000169627), BOLA2 (ENSG00000183336)

Protein

Protein identifiers

BolA-like protein 1 — Q9Y3E2 (reviewed: Q9Y3E2)

Alternative names: hBolA

All UniProt accessions (1): Q9Y3E2

UniProt curated annotations — full annotation on UniProt →

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 the monothiol glutaredoxin GLRX5. May protect cells against oxidative stress.

Subunit / interactions. Interacts with GLRX5.

Subcellular location. Mitochondrion.

Tissue specificity. Widely expressed.

Similarity. Belongs to the BolA/IbaG family.

RefSeq proteins (3): NP_001307954, NP_001307955, NP_057158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002634	BolA	Family
IPR036065	BolA-like_sf	Homologous_superfamily
IPR050961	BolA/IbaG_stress_morph_reg	Family

Pfam: PF01722

UniProt features (13 total): helix 6, strand 3, chain 1, region of interest 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5LCI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3E2-F1	78.40	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 81

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 118 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, RODRIGUES_NTN1_TARGETS_DN, PATIL_LIVER_CANCER, GOBP_CELL_REDOX_HOMEOSTASIS, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_MONOATOMIC_ION_HOMEOSTASIS, ACEVEDO_LIVER_CANCER_UP, DURCHDEWALD_SKIN_CARCINOGENESIS_UP, chr1q21, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP

GO Biological Process (3): intracellular iron ion homeostasis (GO:0006879), iron-sulfur cluster assembly (GO:0016226), cell redox homeostasis (GO:0045454)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): mitochondrion (GO:0005739), iron-sulfur cluster assembly complex (GO:1990229)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
metallo-sulfur cluster assembly	1
cellular homeostasis	1
binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BOLA1	BOLA3	Q53S33	993
BOLA1	GLRX5	Q86SX6	841
BOLA1	NFU1	Q9UMS0	797
BOLA1	ISCA2	Q86U28	775
BOLA1	ISCA1	Q9BUE6	760
BOLA1	IBA57	Q5T440	746
BOLA1	GLRX3	O76003	734
BOLA1	LIAS	O43766	717
BOLA1	ISCU	Q9H1K1	690
BOLA1	CIAPIN1	Q6FI81	666
BOLA1	FDX2	Q6P4F2	666
BOLA1	GLRX	P35754	597
BOLA1	NUBPL	Q8TB37	571
BOLA1	MMS19	Q96T76	563
BOLA1	NFS1	Q9Y697	548

IntAct

79 interactions, top by confidence:

A	B	Type	Score
CIAPIN1	GLRX3	psi-mi:“MI:0914”(association)	0.960
GLRX3	BOLA1	psi-mi:“MI:0915”(physical association)	0.870
BOLA1	GLRX3	psi-mi:“MI:0915”(physical association)	0.870
BIRC2	BOLA1	psi-mi:“MI:0915”(physical association)	0.780
BOLA1	BIRC2	psi-mi:“MI:0915”(physical association)	0.780
COMMD8	VPS26C	psi-mi:“MI:0914”(association)	0.640
GLRX3	KLRG2	psi-mi:“MI:0914”(association)	0.640
BOLA1	GLRX5	psi-mi:“MI:0407”(direct interaction)	0.620
C1orf94	BOLA1	psi-mi:“MI:0915”(physical association)	0.560
XIAP	BOLA1	psi-mi:“MI:0915”(physical association)	0.560
HDX	BOLA1	psi-mi:“MI:0915”(physical association)	0.560
BIRC7	BOLA1	psi-mi:“MI:0915”(physical association)	0.560
TXNRD3	BOLA1	psi-mi:“MI:0915”(physical association)	0.560
ZNF572	BOLA1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (58): BOLA1 (Two-hybrid), BOLA1 (Two-hybrid), C1orf94 (Two-hybrid), BOLA1 (Affinity Capture-MS), BOLA1 (Affinity Capture-MS), BOLA1 (Affinity Capture-MS), BOLA1 (Affinity Capture-MS), BOLA1 (Co-fractionation), BOLA1 (Co-fractionation), PCBP1 (Co-fractionation), BOLA1 (Affinity Capture-MS), BOLA1 (Affinity Capture-MS), GFM1 (Affinity Capture-MS), PMPCB (Affinity Capture-MS), PMPCA (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A2BDX3, A4RPM5, A5GFZ6, A6NK58, B4FAT0, B4NXF7, B6TNK6, O19179, O43323, O95396, O95571, P19971, P55203, P85971, Q02846, Q05922, Q08DH8, Q0VFH3, Q14BV6, Q17CA7, Q1WNP0, Q3KQV9, Q3TW96, Q3UQ84, Q561R2, Q58E95, Q5PQQ1, Q5ZKI2, Q61488, Q66JK4, Q6PAT0, Q7PY41, Q86U10, Q8AWD2, Q8NFV4, Q8VBZ0, Q8VDG5, Q923K4, Q96EY9

Diamond homologs: P0A9W6, P0A9W7, P0A9W8, P33989, P45026, P57465, P73055, Q3T138, Q5RCE5, Q86KD0, Q89AF0, Q8K9G5, Q9D8S9, Q9Y3E2, P0ABE2, P0ABE3, P0ABE4, P43780, P57545, P91375, Q12238, Q3E793, Q56585, Q682I1, Q84W65, Q89AA2, Q8BGS2, Q9FIC3, Q9H3K6, Q9KPS0, P29943, O14280, Q9LF68, Q8K992, P39724, A0A1S4BZI5, A0A1S4CB73, A0A2K8FTP3, A0A509AER3, A1ABL7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BOLA1	“form complex”	“Mitochondrial BOLA1-GLRX5 iron-sulfur cluster assembly complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
iron-sulfur cluster assembly	5	86.0×	8e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

26 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

447 predictions. Top by Δscore:

Variant	Effect	Δscore
1:149888120:TTTT:T	donor_gain	1.0000
1:149888124:G:GG	donor_gain	1.0000
1:149888109:G:GT	donor_gain	0.9900
1:149888119:ATTTT:A	donor_gain	0.9900
1:149888121:TTT:T	donor_gain	0.9900
1:149888122:TT:T	donor_gain	0.9900
1:149888123:TG:T	donor_loss	0.9900
1:149888124:G:GA	donor_loss	0.9900
1:149888125:TA:T	donor_loss	0.9900
1:149888126:AAG:A	donor_loss	0.9900
1:149899451:T:A	acceptor_gain	0.9900
1:149888110:A:T	donor_gain	0.9800
1:149888127:AG:A	donor_loss	0.9800
1:149887966:A:T	donor_gain	0.9700
1:149888353:GA:G	donor_gain	0.9700
1:149888335:A:T	donor_gain	0.9600
1:149888128:G:GG	donor_gain	0.9500
1:149899915:C:T	donor_gain	0.9500
1:149887988:A:AG	donor_gain	0.9400
1:149887989:T:G	donor_gain	0.9400
1:149888127:A:AG	donor_gain	0.9400
1:149888355:G:GG	donor_gain	0.9400
1:149899446:ATT:A	acceptor_gain	0.9400
1:149887984:T:G	donor_gain	0.9300
1:149899446:A:AG	acceptor_gain	0.9300
1:149899447:T:G	acceptor_gain	0.9200
1:149899452:G:A	acceptor_gain	0.9200
1:149899870:AG:A	donor_gain	0.9200
1:149899940:G:GT	donor_gain	0.9200
1:149888128:G:C	donor_loss	0.9000

AlphaMissense

859 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:149900262:T:C	F68S	0.997
1:149900261:T:C	F68L	0.994
1:149900263:C:A	F68L	0.994
1:149900263:C:G	F68L	0.994
1:149900262:T:G	F68C	0.993
1:149900325:T:A	V89D	0.992
1:149900279:A:C	S74R	0.991
1:149900281:C:A	S74R	0.991
1:149900281:C:G	S74R	0.991
1:149900288:T:C	F77L	0.991
1:149900290:C:A	F77L	0.991
1:149900290:C:G	F77L	0.991
1:149900289:T:C	F77S	0.989
1:149900178:T:C	L40S	0.987
1:149900260:C:A	H67Q	0.986
1:149900260:C:G	H67Q	0.986
1:149900288:T:A	F77I	0.984
1:149900289:T:G	F77C	0.984
1:149900319:G:C	R87P	0.984
1:149900361:T:A	V101D	0.984
1:149900233:C:A	H58Q	0.982
1:149900233:C:G	H58Q	0.982
1:149900376:T:A	I106N	0.982
1:149900222:A:C	S55R	0.981
1:149900224:C:A	S55R	0.981
1:149900224:C:G	S55R	0.981
1:149900258:C:G	H67D	0.981
1:149900280:G:T	S74I	0.981
1:149900265:G:C	R69P	0.979
1:149900313:G:C	R85P	0.979

dbSNP variants (sampled 300 via entrez): RS1000326062 (1:149898222 A>G), RS1000376716 (1:149898543 T>C), RS1003949870 (1:149899357 T>G), RS1004298855 (1:149899096 A>G), RS1008713826 (1:149900742 C>A), RS1011656747 (1:149900158 G>T), RS1012388472 (1:149900977 C>A), RS1014438560 (1:149897902 G>T), RS1014903651 (1:149898210 A>G), RS1015238665 (1:149899108 C>T), RS1015935100 (1:149898692 T>C), RS1020848653 (1:149897912 G>A), RS1024206655 (1:149901000 G>T), RS1029365547 (1:149898625 G>T), RS1031769221 (1:149899798 G>A)

Disease associations

OMIM: gene MIM:613181 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012227_1040	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects expression, increases abundance	2
FR900359	increases phosphorylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	decreases phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

11 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery