CIAO2B

Summary

CIAO2B (cytosolic iron-sulfur assembly component 2B, HGNC:24261) is a protein-coding gene on chromosome 16q22.1, encoding Cytosolic iron-sulfur assembly component 2B (Q9Y3D0). Component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins. It is a common-essential gene (DepMap: required in 97.4% of cancer cell lines).

Involved in chromosome segregation and protein maturation. Located in cytosol; nucleoplasm; and spindle. Part of MMXD complex and cytosolic [4Fe-4S] assembly targeting complex.

Source: NCBI Gene 51647 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_016062

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24261
Approved symbol	CIAO2B
Name	cytosolic iron-sulfur assembly component 2B
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CGI-128, MIP18, CIA2B
Ensembl gene	ENSG00000166595
Ensembl biotype	protein_coding
OMIM	614778
Entrez	51647

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000422424, ENST00000562362, ENST00000563490, ENST00000567511, ENST00000568572, ENST00000569299

RefSeq mRNA: 1 — MANE Select: NM_016062 NM_016062

CCDS: CCDS45506

Canonical transcript exons

ENST00000422424 — 5 exons

Exon	Start	End
ENSE00001621441	66933987	66934066
ENSE00001665391	66932065	66932300
ENSE00001687555	66934223	66934402
ENSE00003479677	66932780	66932825
ENSE00003647556	66933614	66933739

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.4264 / max 229.1838, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157733	80.7492	1826
157734	1.9012	1341
157732	0.7761	390

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.07	gold quality
gastrocnemius	UBERON:0001388	98.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.58	gold quality
adenohypophysis	UBERON:0002196	98.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.36	gold quality
spinal cord	UBERON:0002240	98.29	gold quality
mucosa of transverse colon	UBERON:0004991	98.25	gold quality
muscle of leg	UBERON:0001383	98.18	gold quality
heart left ventricle	UBERON:0002084	98.15	gold quality
apex of heart	UBERON:0002098	98.13	gold quality
cardiac ventricle	UBERON:0002082	98.10	gold quality
pituitary gland	UBERON:0000007	98.06	gold quality
left adrenal gland cortex	UBERON:0035825	98.06	gold quality
left adrenal gland	UBERON:0001234	98.02	gold quality
right atrium auricular region	UBERON:0006631	98.00	gold quality
right adrenal gland	UBERON:0001233	97.94	gold quality
esophagus mucosa	UBERON:0002469	97.90	gold quality
prefrontal cortex	UBERON:0000451	97.89	gold quality
anterior cingulate cortex	UBERON:0009835	97.87	gold quality
amygdala	UBERON:0001876	97.86	gold quality
oocyte	CL:0000023	97.85	gold quality
muscle organ	UBERON:0001630	97.85	gold quality
caudate nucleus	UBERON:0001873	97.84	gold quality
cingulate cortex	UBERON:0003027	97.84	gold quality
adrenal cortex	UBERON:0001235	97.83	gold quality
right adrenal gland cortex	UBERON:0035827	97.83	gold quality
nucleus accumbens	UBERON:0001882	97.76	gold quality
ganglionic eminence	UBERON:0004023	97.75	gold quality
left coronary artery	UBERON:0001626	97.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.42
E-MTAB-8142	yes	10.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting CIAO2B, 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-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646
HSA-MIR-4765	93.11	66.17	737

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• these findings suggest that FAM96B acts as a regulator of E2-2 through the control of its protein expression. (PMID:21722264)
• The mammalian proteins MMS19, MIP18, and ANT2 are involved in cytoplasmic iron-sulfur cluster protein assembly. (PMID:23150669)
• CIA2B-CIA1-MMS19 and CIA2A-CIA1 assist different branches of Fe/S protein assembly and intimately link this process to cellular iron regulation via IRP1 Fe/S cluster maturation and IRP2 stabilization. (PMID:23891004)
• Co-localization experiments by fluorescent confocal microscopy revealed that FAM96B colocalized with prelamin A in HEK-293 cells. (PMID:24041693)
• Data suggest that CIA2B and MMS19 physically interact with C-terminus of viperin/RSAD2; CIAO1 appears to function as primary viperin-interacting protein; CIA2A binds to N-terminus of viperin in CIAO1-, CIA2B-, and MMS19-independent fashion. (CIA2B = metallochaperone CIA2B/FAM96B; MMS19 = transcription factor MMS19; CIAO1 = cytosolic iron-sulfur assembly component 1; CIA2A = metallochaperone CIA2A/Fam96a) (PMID:28615450)
• We performed a yeast two-hybrid screen on a human fetal brain cDNA library and identified FAM96B as a novel binding partner of SelW. FRET analyses confirmed the interaction between SelW’ and FAM96B. (PMID:30876693)
• FAM96B inhibits the senescence of dental pulp stem cells. (PMID:32039527)
• Structural insights into Fe-S protein biogenesis by the CIA targeting complex. (PMID:32632277)
• Fam96b recruits brain-type creatine kinase to fuel mitotic spindle formation. (PMID:36503010)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ciao2b	ENSDARG00000052010
mus_musculus	Ciao2b	ENSMUSG00000031879
rattus_norvegicus	Ciao2b	ENSRNOG00000011865
drosophila_melanogaster	galla-2	FBGN0036107
caenorhabditis_elegans		WBGENE00009736

Paralogs (1): CIAO2A (ENSG00000166797)

Protein

Protein identifiers

Cytosolic iron-sulfur assembly component 2B — Q9Y3D0 (reviewed: Q9Y3D0)

Alternative names: MSS19-interacting protein of 18 kDa, Mitotic spindle-associated MMXD complex subunit MIP18, Protein FAM96B

All UniProt accessions (4): Q9Y3D0, H3BNV7, J3KS95, J3QLT9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins. As a CIA complex component and in collaboration with CIAO1 and MMS19, binds to and facilitates the assembly of most cytosolic-nuclear Fe/S proteins. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation, probably by facilitating iron-sulfur cluster assembly into ERCC2/XPD. Together with MMS19, facilitates the transfer of Fe-S clusters to the motor protein KIF4A, which ensures proper localization of KIF4A to mitotic machinery components to promote the progression of mitosis.

Subunit / interactions. Component of the CIA complex. Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5. Interacts with CIAO1, ERCC2 and MMS19; the interactions are direct. Interacts with KIF4A; the interaction facilitates the transfer of Fe-S clusters to KIF4A to ensure proper localization of KIF4A to the mitotic machinery. Interacts with CCDC117; the interaction is direct.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle. Midbody.

Similarity. Belongs to the MIP18 family.

RefSeq proteins (1): NP_057146* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002744	MIP18-like	Domain
IPR034904	FSCA_dom_sf	Homologous_superfamily
IPR039796	MIP18	Family

Pfam: PF01883

UniProt features (2 total): initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3D0-F1	85.56	0.49

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2564830	Cytosolic iron-sulfur cluster assembly

MSigDB gene sets: 99 (showing top): chr16q22, GOBP_PROTEIN_MATURATION, IRF1_Q6, ELK1_01, MCCLUNG_COCAIN_REWARD_4WK, GOCC_SPINDLE, GOCC_MIDBODY, GOBP_CELL_CYCLE_PROCESS, SCGGAAGY_ELK1_02, MULLIGHAN_MLL_SIGNATURE_1_UP, MGGAAGTG_GABP_B, IRITANI_MAD1_TARGETS_UP, GOBP_CHROMOSOME_SEGREGATION, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_17, FORTSCHEGGER_PHF8_TARGETS_DN

GO Biological Process (2): chromosome segregation (GO:0007059), protein maturation (GO:0051604)

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

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), spindle (GO:0005819), cytosol (GO:0005829), midbody (GO:0030496), MMXD complex (GO:0071817), cytosolic [4Fe-4S] assembly targeting complex (GO:0097361), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	2
cell cycle process	1
gene expression	1
protein metabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
cytoplasm	1
spindle	1
protein-containing complex	1
intracellular protein-containing complex	1
iron-sulfur cluster assembly complex	1

Protein interactions and networks

STRING

1232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIAO2B	CIAO1	O76071	998
CIAO2B	MMS19	Q96T76	997
CIAO2B	SLC25A5	P05141	947
CIAO2B	SLC25A6	P12236	945
CIAO2B	CIAO3	Q9H6Q4	878
CIAO2B	NUBP1	P53384	815
CIAO2B	CIAPIN1	Q6FI81	718
CIAO2B	ERCC2	P18074	665
CIAO2B	RTEL1	Q9NZ71	655
CIAO2B	BRIP1	Q9BX63	647
CIAO2B	NDOR1	Q9UHB4	642
CIAO2B	DNA2	P51530	622
CIAO2B	ABCB7	O75027	556
CIAO2B	GLRX3	O76003	527
CIAO2B	NFS1	Q9Y697	519

IntAct

151 interactions, top by confidence:

A	B	Type	Score
CIAO2B	CIAO1	psi-mi:“MI:0915”(physical association)	0.950
CIAO1	CIAO2B	psi-mi:“MI:0915”(physical association)	0.950
CIAO2B	CIAO1	psi-mi:“MI:0914”(association)	0.950
CIAO2B	CIAO1	psi-mi:“MI:0407”(direct interaction)	0.950
MMS19	CIAO1	psi-mi:“MI:0914”(association)	0.910
MMS19	CIAO1	psi-mi:“MI:0915”(physical association)	0.910
MMS19	CIAO2B	psi-mi:“MI:0915”(physical association)	0.830
CIAO2B	MMS19	psi-mi:“MI:0915”(physical association)	0.830
MMS19	CIAO2B	psi-mi:“MI:0407”(direct interaction)	0.830
MMS19	ERCC2	psi-mi:“MI:0915”(physical association)	0.690

BioGRID (175): FAM96B (Two-hybrid), FAM96B (Affinity Capture-MS), FAM96B (Affinity Capture-Western), FAM96B (Affinity Capture-Western), FAM96B (Affinity Capture-MS), FAM96B (Two-hybrid), FAM96B (Co-fractionation), CIAO1 (Two-hybrid), FAM96B (Affinity Capture-MS), FAM96B (Affinity Capture-MS), FAM96B (Affinity Capture-MS), FAM96B (Two-hybrid), FAM96B (Affinity Capture-MS), FAM96B (Affinity Capture-MS), FAM96B (Two-hybrid)

ESM2 similar proteins: A0A096MJN4, A8MR89, B3MRT7, B3NYF7, B4H303, B4IMF6, B4JWR9, B4M375, B4NE93, B4PZ52, B4R3T1, B5DKJ8, O01479, O13718, O43236, O62252, P08761, P15807, P16393, P23337, P28661, P32783, P32860, P38829, P40487, P46580, P53893, Q3T0U7, Q54QK1, Q5R6R7, Q6BYP7, Q6CKE9, Q6CLC9, Q6CPN1, Q6FMP0, Q6FTG1, Q75AZ9, Q8RXN5, Q8SY96, Q92599

Diamond homologs: A8MR89, O62252, P38829, Q3T0U7, Q54QK1, Q9C9G6, Q9D187, Q9DCL2, Q9GPR0, Q9H5X1, Q9SR25, Q9UTL0, Q9V968, Q9VTC4, Q9Y3D0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CIAO2B	“form complex”	“CIAO2B cytosolic iron-sulfur protein assembly complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
Cytosolic iron-sulfur cluster assembly	5	74.6×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

427 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66932299:CA:C	acceptor_gain	0.9900
16:66932301:C:CC	acceptor_gain	0.9900
16:66933609:CTGA:C	donor_loss	0.9900
16:66933610:TGAC:T	donor_loss	0.9900
16:66933611:GAC:G	donor_loss	0.9900
16:66933612:A:T	donor_loss	0.9900
16:66933613:C:CA	donor_loss	0.9900
16:66933646:TG:T	donor_gain	0.9900
16:66933737:AACC:A	acceptor_loss	0.9900
16:66933739:CCTGG:C	acceptor_loss	0.9900
16:66933740:C:CG	acceptor_loss	0.9900
16:66933746:G:C	acceptor_gain	0.9900
16:66932299:CACT:C	acceptor_loss	0.9800
16:66932300:ACTAG:A	acceptor_loss	0.9800
16:66932301:C:A	acceptor_loss	0.9800
16:66932317:G:C	acceptor_gain	0.9800
16:66932779:CCTG:C	donor_gain	0.9800
16:66932825:TC:T	acceptor_loss	0.9800
16:66932826:C:CC	acceptor_gain	0.9800
16:66932827:T:G	acceptor_loss	0.9800
16:66933744:T:C	acceptor_gain	0.9800
16:66933744:T:TC	acceptor_gain	0.9800
16:66934264:T:TA	donor_gain	0.9800
16:66934267:T:TA	donor_gain	0.9800
16:66932297:TTCA:T	acceptor_gain	0.9700
16:66932298:TCA:T	acceptor_gain	0.9700
16:66932299:CAC:C	acceptor_gain	0.9700
16:66932317:G:GC	acceptor_gain	0.9700
16:66932774:ACTT:A	donor_loss	0.9700
16:66932776:TTACC:T	donor_loss	0.9700

AlphaMissense

1057 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:66932261:G:T	A145D	1.000
16:66932264:G:T	A144D	1.000
16:66932268:C:G	A143P	1.000
16:66932273:C:G	R141P	1.000
16:66932276:T:A	E140V	1.000
16:66932277:C:T	E140K	1.000
16:66932278:C:A	K139N	1.000
16:66932278:C:G	K139N	1.000
16:66932281:A:C	D138E	1.000
16:66932281:A:T	D138E	1.000
16:66932282:T:A	D138V	1.000
16:66932283:C:G	D138H	1.000
16:66932288:A:G	L136P	1.000
16:66932288:A:T	L136H	1.000
16:66933642:A:G	L107P	1.000
16:66933660:A:G	L101P	1.000
16:66933663:C:A	G100V	1.000
16:66933663:C:T	G100D	1.000
16:66933664:C:G	G100R	1.000
16:66933666:A:T	I99N	1.000
16:66933683:G:C	C93W	1.000
16:66933684:C:A	C93F	1.000
16:66933684:C:T	C93Y	1.000
16:66933685:A:G	C93R	1.000
16:66933699:G:T	P88Q	1.000
16:66933700:G:A	P88S	1.000
16:66933705:A:G	F86S	1.000
16:66934015:A:G	L65S	1.000
16:66934024:A:T	L62Q	1.000
16:66934035:A:C	H58Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000406021 (16:66935881 C>CTCCTAGAA), RS1000967376 (16:66933369 A>C), RS1002764377 (16:66932782 G>A,C), RS1002905238 (16:66934168 T>C), RS1003225189 (16:66932478 C>T), RS1003292966 (16:66935607 G>A,C,T), RS1005153402 (16:66934966 C>T), RS1005358757 (16:66932004 TC>T,TCC,TCCC), RS1006456135 (16:66931734 T>A), RS1006618489 (16:66932327 G>A,C,T), RS1006669721 (16:66932069 T>C), RS1007251442 (16:66933345 G>C), RS1007609862 (16:66933078 C>T), RS1008958168 (16:66933928 G>A), RS1011410420 (16:66932446 A>C)

Disease associations

OMIM: gene MIM:614778 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295989 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11075646	CES2, CIAO2B		0.00	0

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	increases expression, increases abundance	2
Rotenone	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
pyrimidifen	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Vitamin E	increases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118721	Binding	Binding affinity to FAM96B in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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