BOLA2B

Summary

BOLA2B (bolA family member 2B, HGNC:32479) is a protein-coding gene on chromosome 16p11.2, encoding BolA-like protein 2 (Q9H3K6). Acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins.

This gene is located within a region of a segmental duplication on chromosome 16 and is identical to BOLA2 (bolA family member 2). The product of this gene belongs to a family of proteins that are widely conserved and may be involved in iron maturation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 654483 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001039182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32479
Approved symbol	BOLA2B
Name	bolA family member 2B
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169627
Ensembl biotype	protein_coding
Entrez	654483

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000305321, ENST00000565525, ENST00000567436, ENST00000569282, ENST00000651894, ENST00000922578, ENST00000948891

RefSeq mRNA: 2 — MANE Select: NM_001039182 NM_001039182, NM_001320607

CCDS: CCDS32430, CCDS92138

Canonical transcript exons

ENST00000651894 — 3 exons

Exon	Start	End
ENSE00001738107	30193358	30193455
ENSE00002593583	30193533	30193666
ENSE00003890283	30192932	30193074

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.56.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4891 / max 11.7358, expressed in 264 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157035	0.4891	264

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.56	gold quality
granulocyte	CL:0000094	97.28	gold quality
stromal cell of endometrium	CL:0002255	97.15	gold quality
lower esophagus mucosa	UBERON:0035834	96.99	gold quality
bone marrow cell	CL:0002092	96.96	gold quality
apex of heart	UBERON:0002098	96.88	gold quality
prefrontal cortex	UBERON:0000451	96.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.59	gold quality
primary visual cortex	UBERON:0002436	96.54	gold quality
cortex of kidney	UBERON:0001225	96.49	gold quality
duodenum	UBERON:0002114	96.32	gold quality
substantia nigra	UBERON:0002038	96.22	gold quality
vermiform appendix	UBERON:0001154	96.16	gold quality
temporal lobe	UBERON:0001871	96.15	gold quality
amygdala	UBERON:0001876	96.13	gold quality
esophagus mucosa	UBERON:0002469	95.95	gold quality
adenohypophysis	UBERON:0002196	95.90	gold quality
lymph node	UBERON:0000029	95.89	gold quality
pituitary gland	UBERON:0000007	95.88	gold quality
bone marrow	UBERON:0002371	95.87	gold quality
adult mammalian kidney	UBERON:0000082	95.86	gold quality
putamen	UBERON:0001874	95.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.63	gold quality
hypothalamus	UBERON:0001898	95.58	gold quality
spleen	UBERON:0002106	95.56	gold quality
Ammon’s horn	UBERON:0001954	95.47	gold quality
transverse colon	UBERON:0001157	95.46	gold quality
nucleus accumbens	UBERON:0001882	95.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.17	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	2145.28
E-HCAD-8	yes	56.82
E-MTAB-8410	yes	22.80
E-HCAD-9	yes	18.41
E-ANND-3	yes	12.71
E-HCAD-1	yes	10.40
E-GEOD-83139	no	2.75

Regulation

Is transcription factor: no

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	BOLA2B	ENSDARG00000111714
mus_musculus	Bola2	ENSMUSG00000047721
rattus_norvegicus	Bola2-ps1	ENSRNOG00000015333
rattus_norvegicus	AABR07034928.1	ENSRNOG00000034215
rattus_norvegicus	Bola2	ENSRNOG00000047988
drosophila_melanogaster	CG33672	FBGN0061360

Paralogs (3): BOLA3 (ENSG00000163170), BOLA1 (ENSG00000178096), BOLA2 (ENSG00000183336)

Protein

Protein identifiers

BolA-like protein 2 — Q9H3K6 (reviewed: Q9H3K6)

All UniProt accessions (4): Q9H3K6, A0A499FJE1, H3BPT9, H3BTW0

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins. Acts together with the monothiol glutaredoxin GLRX3.

Subunit / interactions. Interacts with GLRX3; forms a heterotrimeric complex composed by two BOLA2 molecules and one GLRX3 molecule; linked by [2Fe-2S] clusters.

Subcellular location. Cytoplasm. Nucleus.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the BolA/IbaG family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H3K6-1	1	yes
Q9H3K6-2	2

RefSeq proteins (2): NP_001034271, NP_001307536 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002634	BolA	Family
IPR036065	BolA-like_sf	Homologous_superfamily
IPR045115	BOL2	Family

Pfam: PF01722

UniProt features (4 total): splice variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3K6-F1	92.72	0.83

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): 1

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-9020591	Interleukin-12 signaling

MSigDB gene sets: 22 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_PROTEIN_MATURATION, GOBP_CELL_REDOX_HOMEOSTASIS, chr16p11, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOMF_METAL_CLUSTER_BINDING, GOMF_2_IRON_2_SULFUR_CLUSTER_BINDING, GOBP_2FE_2S_CLUSTER_ASSEMBLY, REACTOME_INTERLEUKIN_12_FAMILY_SIGNALING, REACTOME_GENE_AND_PROTEIN_EXPRESSION_BY_JAK_STAT_SIGNALING_AFTER_INTERLEUKIN_12_STIMULATION, REACTOME_INTERLEUKIN_12_SIGNALING, HOEK_MYELOID_DENDRITIC_CELL_2011_2012_TIV_ADULT_7DY_UP

GO Biological Process (5): intracellular iron ion homeostasis (GO:0006879), iron-sulfur cluster assembly (GO:0016226), [2Fe-2S] cluster assembly (GO:0044571), cell redox homeostasis (GO:0045454), protein maturation (GO:0051604)

GO Molecular Function (3): iron-sulfur cluster binding (GO:0051536), 2 iron, 2 sulfur cluster binding (GO:0051537), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), iron-sulfur cluster assembly complex (GO:1990229)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Interleukin-12 signaling	1
Immune System	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Interleukin-12 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
metallo-sulfur cluster assembly	1
iron-sulfur cluster assembly	1
cellular homeostasis	1
gene expression	1
protein metabolic process	1
metal cluster binding	1
iron-sulfur cluster binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

1132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BOLA2B	BOLA3	Q53S33	986
BOLA2B	GLRX3	O76003	943
BOLA2B	GLRX5	Q86SX6	746
BOLA2B	CIAPIN1	Q6FI81	717
BOLA2B	NFU1	Q9UMS0	577
BOLA2B	LIAS	O43766	543
BOLA2B	NDOR1	Q9UHB4	543
BOLA2B	GPHRA	B7ZAQ6	528
BOLA2B	MMS19	Q96T76	518
BOLA2B	BOLA1	Q9Y3E2	517
BOLA2B	SRGAP2C	P0DJJ0	502
BOLA2B	ISCA2	Q86U28	497
BOLA2B	GLRX	P35754	496
BOLA2B	ISCU	Q9H1K1	496
BOLA2B	ARHGAP11B	Q3KRB8	479

IntAct

90 interactions, top by confidence:

A	B	Type	Score
CIAPIN1	GLRX3	psi-mi:“MI:0914”(association)	0.960
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GLRX3	KLRG2	psi-mi:“MI:0914”(association)	0.640
KLRG2	GLRX3	psi-mi:“MI:0914”(association)	0.640
GLRX3	BOLA2	psi-mi:“MI:0915”(physical association)	0.560
BOLA2	GLRX3	psi-mi:“MI:0915”(physical association)	0.560
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
CIAPIN1	BOLA2	psi-mi:“MI:0915”(physical association)	0.500
NDOR1	BOLA2	psi-mi:“MI:0915”(physical association)	0.400
BOLA2	NARF	psi-mi:“MI:0915”(physical association)	0.400
BOLA2	SNCA	psi-mi:“MI:0915”(physical association)	0.400
MAPK6		psi-mi:“MI:0914”(association)	0.350
ARRB2		psi-mi:“MI:0914”(association)	0.350
CDK1	RBMXL2	psi-mi:“MI:0914”(association)	0.350
COQ2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
COX15	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350
PARK7	SAP18	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
VDAC1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
DLD	EIF3D	psi-mi:“MI:0914”(association)	0.350

BioGRID (192): BOLA2 (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), BOLA2B (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), BOLA2B (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), BOLA2B (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), BOLA2B (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), BOLA2B (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), BOLA2B (Affinity Capture-MS)

ESM2 similar proteins: A1A4Q2, A1YER2, A1YFX9, A2T7G9, A6QP05, B0BN93, B0BNF8, B2GV38, O35331, O80526, O95154, O95671, P10950, P11172, P11441, P13439, P21126, P46597, P50053, P84169, Q0VCN1, Q28DS0, Q2HJF1, Q2QNG7, Q2QZ86, Q3T138, Q3TY86, Q5E964, Q5I0K3, Q5R4T1, Q5R514, Q5R8R4, Q5RB44, Q6P637, Q8BGS2, Q8CG45, Q8CG76, Q8CI33, Q8HZJ0, Q8JGT5

Diamond homologs: O14280, P39724, P53082, P91375, Q3SZ84, Q53S33, Q84W65, Q86HT3, Q8BGS2, Q8CEI1, Q9FIC3, Q9H3K6, Q9KPS0, Q9USK1, P0ABE2, P0ABE3, P0ABE4, P43780, P57545, Q12238, Q3E793, Q3T138, Q56585, Q5RCE5, Q682I1, Q86KD0, Q89AA2, Q9D8S9, Q9Y3E2, P29943, P73055, P0A9W6, P0A9W7, P0A9W8, Q9LF68, P45026, Q8K992, A0A1S4BZI5, A0A1S4CB73, A0A2K8FTP3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BOLA2	“form complex”	“BOLA2-GLRX3 iron-sulfur cluster assembly complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by high-kinase activity BRAF mutants	5	22.0×	2e-04
Signaling by FGFR1 in disease	5	20.3×	2e-04
MAP2K and MAPK activation	5	19.8×	3e-04
Signaling by moderate kinase activity BRAF mutants	5	17.6×	3e-04
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	17.6×	3e-04
Signaling downstream of RAS mutants	5	17.6×	3e-04
Signaling by BRAF and RAF1 fusions	6	14.2×	2e-04
Regulation of RAS by GAPs	5	13.4×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2570962	GRCh37/hg19 16p11.2(chr16:29675050-30218384)x1	Pathogenic

SpliceAI

422 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30193525:CAACT:C	donor_loss	0.9900
16:30193526:AACTC:A	donor_loss	0.9900
16:30193527:ACT:A	donor_loss	0.9900
16:30193528:CT:C	donor_loss	0.9900
16:30193529:TCA:T	donor_loss	0.9900
16:30193530:C:CG	donor_loss	0.9900
16:30193531:A:AC	donor_gain	0.9900
16:30193531:ACCAC:A	donor_loss	0.9900
16:30193532:C:CC	donor_gain	0.9900
16:30193532:C:G	donor_loss	0.9900
16:30193532:CCA:C	donor_gain	0.9900
16:30193352:CCTTA:C	donor_loss	0.9800
16:30193353:CTTA:C	donor_loss	0.9800
16:30193354:TTA:T	donor_loss	0.9800
16:30193355:TA:T	donor_loss	0.9800
16:30193356:A:AT	donor_loss	0.9800
16:30193524:TCAAC:T	donor_loss	0.9800
16:30193527:A:C	donor_gain	0.9800
16:30194030:GACCC:G	donor_gain	0.9800
16:30194262:C:T	donor_gain	0.9700
16:30194303:G:GT	donor_gain	0.9700
16:30193070:CCAGC:C	acceptor_gain	0.9600
16:30193071:CAGCC:C	acceptor_gain	0.9600
16:30193454:TCCTA:T	acceptor_loss	0.9600
16:30193455:CCTAC:C	acceptor_loss	0.9600
16:30193457:T:G	acceptor_loss	0.9600
16:30194240:C:T	donor_gain	0.9600
16:30193356:A:AC	donor_gain	0.9500
16:30193357:C:CC	donor_gain	0.9500
16:30193452:CCTC:C	acceptor_gain	0.9500

AlphaMissense

553 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30193387:G:C	F44L	0.992
16:30193387:G:T	F44L	0.992
16:30193389:A:G	F44L	0.992
16:30193362:G:C	H53D	0.984
16:30193069:A:T	V56E	0.982
16:30193403:A:T	V39E	0.982
16:30193027:A:G	F70S	0.981
16:30193414:G:C	F35L	0.981
16:30193414:G:T	F35L	0.981
16:30193416:A:G	F35L	0.981
16:30193388:A:G	F44S	0.980
16:30193409:A:T	V37D	0.978
16:30193370:A:T	L50H	0.977
16:30193389:A:T	F44I	0.972
16:30193561:A:G	L12P	0.972
16:30193034:G:C	H68D	0.971
16:30193032:A:C	H68Q	0.970
16:30193032:A:T	H68Q	0.970
16:30193045:A:G	L64P	0.970
16:30193074:C:A	R54S	0.970
16:30193074:C:G	R54S	0.970
16:30193363:T:A	R52S	0.970
16:30193363:T:G	R52S	0.970
16:30193400:A:T	V40E	0.970
16:30193573:A:T	L8H	0.970
16:30193398:A:G	S41P	0.969
16:30193415:A:G	F35S	0.969
16:30193561:A:T	L12Q	0.969
16:30193012:A:G	L75P	0.967
16:30193364:C:G	R52T	0.967

dbSNP variants (sampled 300 via entrez): RS1003660683 (16:30194786 C>T), RS1012919487 (16:30194823 G>A,T), RS1015002392 (16:30194881 C>A,G,T), RS1027624502 (16:30194827 G>A), RS1158214601 (16:30194904 C>T), RS1159511580 (16:30194479 C>G), RS1159665083 (16:30194800 G>A), RS1160221756 (16:30195147 G>A), RS1162414009 (16:30194840 G>A,T), RS1163232534 (16:30194866 C>T), RS1164063339 (16:30194631 A>G), RS1166126705 (16:30194668 C>T), RS1169709236 (16:30195166 A>T), RS1170387622 (16:30194221 A>C,G), RS1170815822 (16:30194967 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_269	Brain morphology (MOSTest)	4.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724752 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178999: Inhibition of BOLA2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
butyraldehyde	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650994	Binding	Binding affinity to human BOLA2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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