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 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 35 total
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Cancer dependency (DepMap): dependent in 97.4% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.68 (unconstrained)
• 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: 12 — 9 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000422424

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 1, TSL 5: 2

ENST00000422424, ENST00000562362, ENST00000563490, ENST00000567511, ENST00000568572, ENST00000569299, ENST00001088370, ENST00001093019, ENST00001115439, ENST00001115440, ENST00001126228, ENST00001136950

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.

Highest expression (Bgee): lower esophagus mucosa, gastrocnemius, hindlimb stylopod muscle, C1 segment of cervical spinal cord, adenohypophysis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CIAO2B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	3.1e-19	-0.30	16:66900250:T:C
Testis	eqtl	3.5e-03	-0.38	16:67201353:A:G
Skin Sun Exposed Lower leg	eqtl	2.1e-02	-0.21	16:67849291:G:A
Breast Mammary Tissue	eqtl	3.1e-02	-0.30	16:66350252:TA:T
Esophagus Gastroesophageal Junction	eqtl	3.3e-02	+0.30	16:67664019:C:T
Esophagus Muscularis	eqtl	4.1e-02	+0.32	16:67077227:G:A

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

showing 100 of 288 tissues 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
metanephros cortex	UBERON:0010533	97.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.68	gold quality
stromal cell of endometrium	CL:0002255	97.67	gold quality
esophagus	UBERON:0001043	97.63	gold quality
cerebellar hemisphere	UBERON:0002245	97.63	gold quality
lower esophagus	UBERON:0013473	97.63	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.63	gold quality
cerebellar cortex	UBERON:0002129	97.62	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.62	gold quality
heart	UBERON:0000948	97.57	gold quality
heart right ventricle	UBERON:0002080	97.54	gold quality
left ovary	UBERON:0002119	97.54	gold quality
adult organism	UBERON:0007023	97.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.54	gold quality
tibialis anterior	UBERON:0001385	97.53	gold quality
right frontal lobe	UBERON:0002810	97.53	gold quality
pharyngeal mucosa	UBERON:0000355	97.52	gold quality
left lobe of thyroid gland	UBERON:0001120	97.51	gold quality
ascending aorta	UBERON:0001496	97.48	gold quality
thoracic aorta	UBERON:0001515	97.48	gold quality
coronary artery	UBERON:0001621	97.48	gold quality
popliteal artery	UBERON:0002250	97.48	gold quality
tibial artery	UBERON:0007610	97.47	gold quality
aorta	UBERON:0000947	97.45	gold quality
biceps brachii	UBERON:0001507	97.45	gold quality
putamen	UBERON:0001874	97.45	gold quality
tibial nerve	UBERON:0001323	97.42	gold quality
triceps brachii	UBERON:0001509	97.42	gold quality
right ovary	UBERON:0002118	97.39	gold quality
left uterine tube	UBERON:0001303	97.38	gold quality
cerebellum	UBERON:0002037	97.35	gold quality
body of tongue	UBERON:0011876	97.34	gold quality
endocervix	UBERON:0000458	97.33	gold quality
right coronary artery	UBERON:0001625	97.33	gold quality
cardiac atrium	UBERON:0002081	97.32	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.32	gold quality
right testis	UBERON:0004534	97.26	gold quality
transverse colon	UBERON:0001157	97.24	gold quality
deltoid	UBERON:0001476	97.24	gold quality
right lung	UBERON:0002167	97.24	gold quality
ectocervix	UBERON:0012249	97.24	gold quality
descending thoracic aorta	UBERON:0002345	97.23	gold quality
left testis	UBERON:0004533	97.22	gold quality
upper lobe of left lung	UBERON:0008952	97.22	gold quality
adult mammalian kidney	UBERON:0000082	97.20	gold quality
skeletal muscle tissue	UBERON:0001134	97.17	gold quality
right lobe of thyroid gland	UBERON:0001119	97.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.13	gold quality
right lobe of liver	UBERON:0001114	97.08	gold quality
hypothalamus	UBERON:0001898	97.08	gold quality
body of uterus	UBERON:0009853	97.07	gold quality
peritoneum	UBERON:0002358	97.05	gold quality
omental fat pad	UBERON:0010414	97.05	gold quality
granulocyte	CL:0000094	97.04	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.03	gold quality
upper lobe of lung	UBERON:0008948	97.00	gold quality
body of stomach	UBERON:0001161	96.96	gold quality
ventricular zone	UBERON:0003053	96.92	gold quality
mucosa of stomach	UBERON:0001199	96.90	gold quality
gluteal muscle	UBERON:0002000	96.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.90	gold quality
neocortex	UBERON:0001950	96.88	gold quality
adrenal gland	UBERON:0002369	96.88	gold quality
cortical plate	UBERON:0005343	96.88	gold quality
thyroid gland	UBERON:0002046	96.87	gold quality
frontal cortex	UBERON:0001870	96.83	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.80	gold quality
colon	UBERON:0001155	96.76	gold quality
forebrain	UBERON:0001890	96.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.67	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	228.8	medium
Heart muscle	tissue	126.4	medium
Tongue	tissue	111.8
Pituitary gland	tissue	108.0
Parathyroid gland	tissue	107.8	low
Esophagus	tissue	97.0	medium
Liver	tissue	86.4	low
Vagina	tissue	81.0	medium
Locus coeruleus	tissue	80.6
Lymph node	tissue	78.1	medium
Spinal cord	tissue	77.8
Putamen	tissue	75.8
Nucleus accumbens	tissue	75.2
Kidney	tissue	74.2	medium
Adrenal gland	tissue	73.8	medium
Hippocampus	tissue	73.6	medium
Septum	tissue	71.8
Pons	tissue	71.6
Medulla oblongata	tissue	71.1
Corpus callosum	tissue	70.9
Ovary	tissue	70.1	low
Basal ganglia	tissue	69.6	medium
Thyroid gland	tissue	69.2	low
Midbrain	tissue	69.0
Choroid plexus	tissue	68.7
Hippocampal formation	tissue	68.4
Postcentral gyrus	tissue	66.5
Colon	tissue	65.9	medium
Ventral forebrain	tissue	65.7
Urinary bladder	tissue	65.4	medium
Thymus	tissue	65.1
Substantia nigra	tissue	64.6
Small intestine	tissue	63.7	medium
Thalamus	tissue	63.4
Fallopian tube	tissue	62.1	medium
Placenta	tissue	62.0	medium
Superior colliculi	tissue	60.8
Cerebral cortex	tissue	60.6	medium
Somatosensory cortex	tissue	60.6
Hypothalamus	tissue	59.4
Duodenum	tissue	59.4	low
Tonsil	tissue	59.2	medium
Epididymis	tissue	58.9	medium
Occipital cortex	tissue	56.3
Stomach 1	tissue	56.2	medium
Rectum	tissue	56.1	medium
Spleen	tissue	56.0	medium
Appendix	tissue	55.8	medium
Pancreas	tissue	55.7	medium
Periaqueductal gray	tissue	55.1
Gallbladder	tissue	54.2	low
Motor cortex	tissue	53.1
Entorhinal cortex	tissue	53.1
Lung	tissue	52.5	medium
Prefrontal cortex	tissue	52.3
Temporal cortex	tissue	52.1
Adipose tissue	tissue	51.2	medium
Retrosplenial and cingulate cortex	tissue	50.0
Salivary gland	tissue	49.8	low
Smooth muscle	tissue	49.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Lateral funiculus (white matter) (112.2), Cerebellar nuclei (110.0), Dorsal funiculus (white matter) (109.1), Cerebellar white matter (106.8), Anterior funiculus (white matter) (105.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CIAO2B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

16 miRNAs:

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

gnomAD constraint: pLI 1.99e-08, LOEUF 1.68, missense Z 0.0557 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000422424 — one region, missense o/e 0.97. DepMap (CRISPR cell-line fitness): dependent in 97.4% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): KP-N-YN (-2.344), LS1034 (-2.298), OUMS-23 (-2.205), OCUM-1 (-2.128), SK-N-FI (-2.071), SCC-25 (-2.056), KALS-1 (-2.056), SUP-M2 (-1.889), RCC10RGB (-1.85), NCI-H2052 (-1.845), SNU-1033 (-1.845), CL-11 (-1.844), OV-90 (-1.827), SNU-840 (-1.796), HCC-827 (-1.79).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915773) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased neutrophil cell number	1
abnormal heart morphology	1
enlarged heart	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal skin morphology	1
increased spleen weight	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3T0U7	96.9%	Diamond
Schizosaccharomyces pombe 972h-	Q9UTL0	61.2%	Diamond
Dictyostelium discoideum	Q54QK1	60.9%	Diamond
Arabidopsis thaliana	Q9C9G6	60.5%	Diamond
Saccharomyces cerevisiae S288C	P38829	55.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RRAD	protein-coding	6236
CES3	protein-coding	23491
CES4A	protein-coding	283848
CES2	protein-coding	8824
CDH16	protein-coding	1014

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH supported · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 2; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

2 pathways:

ID	Pathway	Evidence
R-HSA-2564830	Cytosolic iron-sulfur cluster assembly	electronic
R-HSA-1430728	Metabolism	—

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 (3): chromosome segregation (GO:0007059), iron-sulfur cluster assembly (GO:0016226), protein maturation (GO:0051604)

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

GO Cellular Component (8): 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)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Metabolism	1

GO top-level categories

16 GO namespaces:

Category	Terms
cellular anatomical structure	4
cell cycle process	1
metallo-sulfur cluster assembly	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
intracellular membraneless organelle	1
cytoplasm	1
spindle	1
protein-containing complex	1
intracellular protein-containing complex	1
iron-sulfur cluster assembly complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
chromosome segregation	BP	mutant phenotype
protein maturation	BP	mutant phenotype
MMXD complex	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
cytosolic [4Fe-4S] assembly targeting complex	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
spindle	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,376 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIAO2B	MMS19	Q96T76	861
CIAO2B	CIAO1	O76071	843
CIAO2B	CIAO3	Q9H6Q4	747
CIAO2B	NUBP1	P53384	720
CIAO2B	CIAPIN1	Q6FI81	713
CIAO2B	NDOR1	Q9UHB4	658
CIAO2B	ERCC2	P18074	593
CIAO2B	ABCB7	O75027	556
CIAO2B	GLRX3	O76003	536
CIAO2B	ISCU	Q9H1K1	518
CIAO2B	NFS1	Q9Y697	499
CIAO2B	ISCA1	Q9BUE6	498
CIAO2B	HSCB	Q8IWL3	496
CIAO2B	FBXL5	Q9UKA1	488
CIAO2B	POLD1	P28340	462

IntAct

Human interaction partners of CIAO2B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 31 partners by confidence:

Partner	Interaction type	MIscore	Records
CIAO1	physical association	0.950	22
MMS19	physical association	0.830	4
ERCC2	direct interaction	0.590	1
CASP6	physical association	0.560	3
CCK	physical association	0.560	3
FGFR3	physical association	0.560	3
GRIN2C	physical association	0.560	3
GRN	physical association	0.560	3
GSN	physical association	0.560	3
HSPB1	physical association	0.560	3
KIF1B	physical association	0.560	3
LAMP2	physical association	0.560	3
PECAM1	physical association	0.560	3
PRPF40A	physical association	0.560	3
PRPS1	physical association	0.560	3
RAB5A	physical association	0.560	3
RAN	physical association	0.560	3
TTR	physical association	0.560	3
UBE2K	physical association	0.560	3
VIM	physical association	0.560	3
WFS1	physical association	0.560	3
BRIP1	direct interaction	0.440	1
LRRC59	physical association	0.400	1
E6	physical association	0.370	3
PB2	physical association	0.370	1
ZNF16	physical association	0.370	1
ELP1	association	0.350	1
DSCAM	physical association	0.000	1
MLF2	physical association	0.000	1
MTNR1A	physical association	0.000	1

SIGNOR signaling

1 signaling interactions:

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

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
MMXD complex	5	CIAO2B, ERCC2, MMS19, SLC25A5, CIAO1
MMS19 complex	4	CIAO1, CIAO2B, CIAO3, MMS19
CIAO1-CIAO2B-MMS19 complex	3	CIAO1, CIAO2B, MMS19
MMS19-FAM96B complex	2	CIAO2B, MMS19

Disease & clinical

Genetic variants

Variant evidence for CIAO2B: 35 ClinVar records (0 pathogenic / likely pathogenic).

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 241):

Position(s)	Effect	Δscore	Sites
16:66933612–66933613	donor_loss	0.9900	5
16:66933740–66933741	acceptor_loss	0.9900	5
16:66933746	acceptor_gain	0.9900
16:66932301–66932302	acceptor_loss	0.9800	6
16:66932317	acceptor_gain	0.9800
16:66932826–66932827	acceptor_loss	0.9800	5
16:66933741	acceptor_loss	0.9800
16:66933744	acceptor_gain	0.9800
16:66932305	acceptor_gain	0.9700
16:66932778–66932779	donor_loss	0.9700	5

AlphaMissense

648 missense substitutions predicted likely pathogenic (of 1,057 scored), across 124 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M95	9	0.946	0.999
D55	8	1.000	1.000
D138	8	0.999	1.000
H126	8	0.996	0.999
H58	8	0.994	1.000
N148	8	0.993	0.999
N14	8	0.992	0.996
D42	8	0.980	0.997
H92	8	0.979	0.998
F86	8	0.976	1.000
D48	8	0.974	0.997
S94	8	0.974	0.999
N133	8	0.949	0.999
D39	8	0.875	0.971
F47	7	0.999	1.000
C93	7	0.999	1.000
E140	7	0.998	1.000
E57	7	0.997	0.999
E147	7	0.993	0.998
F115	7	0.989	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:614778 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295989 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

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 abundance, increases expression	2
Rotenone	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	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)

Via MONDO — disease-level, not drug-specific.