CIAO2A

Summary

CIAO2A (cytosolic iron-sulfur assembly component 2A, HGNC:26235) is a protein-coding gene on chromosome 15q22.31, encoding Cytosolic iron-sulfur assembly component 2A (Q9H5X1). 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 selective cancer dependency (DepMap: 21.2% of cell lines).

Predicted to enable metal ion binding activity. Involved in iron-sulfur cluster assembly and protein maturation. Located in cytosol and nucleoplasm. Part of cytosolic [4Fe-4S] assembly targeting complex.

Source: NCBI Gene 84191 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 33 total
• GTEx eGene: eQTL in 12 tissues, sQTL in 31 (q < 0.05)
• Cancer dependency (DepMap): dependent in 21.2% of screened cell lines
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 1.05 (unconstrained)
• MANE Select transcript: NM_032231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26235
Approved symbol	CIAO2A
Name	cytosolic iron-sulfur assembly component 2A
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22875, CIA2A
Ensembl gene	ENSG00000166797
Ensembl biotype	protein_coding
OMIM	618382
Entrez	84191

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 19 protein_coding, 8 nonsense_mediated_decay

MANE Select: ENST00000300030

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

ENST00000300030, ENST00000380290, ENST00000557835, ENST00000558779, ENST00000559705, ENST00000559950, ENST00000851936, ENST00000851937, ENST00000851938, ENST00000927117, ENST00000927118, ENST00000927119, ENST00000977748, ENST00000977749, ENST00000977750, ENST00000977751, ENST00000977752, ENST00000977753, ENST00001065846, ENST00001065848, ENST00001065849, ENST00001065853, ENST00001102873, ENST00001102874, ENST00001102875, ENST00001102876, ENST00001132801

RefSeq mRNA: 3 — MANE Select: NM_032231 NM_001014812, NM_001289108, NM_032231

CCDS: CCDS10189, CCDS45278

Canonical transcript exons

ENST00000300030 — 5 exons

Exon	Start	End
ENSE00001724296	64072565	64073028
ENSE00001865659	64093645	64093838
ENSE00003615251	64075492	64075537
ENSE00003638599	64088687	64088851
ENSE00003666390	64081102	64081151

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 86.1553 / max 610.0781, expressed in 1827 samples.

Highest expression (Bgee): ileal mucosa, lobe of liver, jejunal mucosa, ventricle myocardium, duodenum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CIAO2A is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 31 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 43 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	2.6e-45	-0.95	15:64090212:G:A
Cells Cultured fibroblasts	sqtl	9.1e-45	-0.92	15:64070537:CTT:C
Lung	sqtl	5.5e-28	+0.81	15:64108050:C:A
Artery Tibial	sqtl	1.6e-25	-0.80	15:64090212:G:A
Adipose Subcutaneous	sqtl	5.6e-24	-0.74	15:64060835:G:T
Adipose Visceral Omentum	sqtl	2.2e-23	-0.76	15:64090698:C:T
Breast Mammary Tissue	sqtl	3.4e-22	+0.89	15:64085036:G:GAGCCAAGAATGC
Nerve Tibial	sqtl	9.6e-21	-0.72	15:64090212:G:A
Esophagus Mucosa	sqtl	1.3e-17	-0.75	15:64090830:G:A
Cells EBV-transformed lymphocytes	eqtl	2.7e-17	-0.30	15:64090212:G:A
Colon Sigmoid	sqtl	4.7e-16	-0.75	15:64090212:G:A
Artery Aorta	sqtl	4.8e-16	+0.70	15:64117349:A:G
Stomach	sqtl	1.8e-15	-0.78	15:64063083:C:G
Pancreas	sqtl	5.8e-15	-0.84	15:64090212:G:A
Esophagus Muscularis	sqtl	7.9e-14	-0.65	15:64090212:G:A
Adrenal Gland	sqtl	1.5e-13	-0.95	15:64090212:G:A
Skin Not Sun Exposed Suprapubic	sqtl	5.0e-12	+0.55	15:64105977:G:A
Prostate	sqtl	5.0e-12	+0.92	15:64126198:G:A
Colon Transverse	sqtl	1.3e-10	-0.55	15:64097544:C:T
Esophagus Gastroesophageal Junction	sqtl	5.3e-10	-0.73	15:64090212:G:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
150448	64.1973	1826
150449	15.9368	1784
150450	6.0211	1577

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.11	gold quality
right lobe of liver	UBERON:0001114	98.62	gold quality
jejunal mucosa	UBERON:0000399	98.56	gold quality
left ventricle myocardium	UBERON:0006566	98.50	gold quality
duodenum	UBERON:0002114	98.12	gold quality
jejunum	UBERON:0002115	98.07	gold quality
monocyte	CL:0000576	98.05	gold quality
kidney epithelium	UBERON:0004819	98.05	gold quality
leukocyte	CL:0000738	97.97	gold quality
mucosa of transverse colon	UBERON:0004991	97.95	gold quality
right adrenal gland	UBERON:0001233	97.66	gold quality
metanephros	UBERON:0000081	97.62	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.61	gold quality
right adrenal gland cortex	UBERON:0035827	97.61	gold quality
colonic mucosa	UBERON:0000317	97.60	gold quality
palpebral conjunctiva	UBERON:0001812	97.53	gold quality
liver	UBERON:0002107	97.52	gold quality
pancreatic ductal cell	CL:0002079	97.48	gold quality
left adrenal gland	UBERON:0001234	97.43	gold quality
epithelium of nasopharynx	UBERON:0001951	97.42	gold quality
quadriceps femoris	UBERON:0001377	97.38	gold quality
lymph node	UBERON:0000029	97.37	gold quality
adrenal tissue	UBERON:0018303	97.37	gold quality
vastus lateralis	UBERON:0001379	97.34	gold quality
left adrenal gland cortex	UBERON:0035825	97.31	gold quality
myocardium	UBERON:0002349	97.27	gold quality
adrenal cortex	UBERON:0001235	97.22	gold quality
rectum	UBERON:0001052	97.07	gold quality
deltoid	UBERON:0001476	97.06	gold quality
cortex of kidney	UBERON:0001225	97.05	gold quality
tibialis anterior	UBERON:0001385	97.05	gold quality
body of pancreas	UBERON:0001150	97.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.04	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.01	gold quality
thymus	UBERON:0002370	96.99	gold quality
metanephros cortex	UBERON:0010533	96.88	gold quality
left lobe of thyroid gland	UBERON:0001120	96.84	gold quality
adrenal gland	UBERON:0002369	96.81	gold quality
adult mammalian kidney	UBERON:0000082	96.77	gold quality
right lobe of thyroid gland	UBERON:0001119	96.71	gold quality
renal medulla	UBERON:0000362	96.64	gold quality
amniotic fluid	UBERON:0000173	96.61	gold quality
thyroid gland	UBERON:0002046	96.59	gold quality
trabecular bone tissue	UBERON:0002483	96.55	gold quality
ventricular zone	UBERON:0003053	96.52	gold quality
body of tongue	UBERON:0011876	96.51	gold quality
biceps brachii	UBERON:0001507	96.46	gold quality
pigmented layer of retina	UBERON:0001782	96.42	gold quality
adult organism	UBERON:0007023	96.42	gold quality
granulocyte	CL:0000094	96.41	gold quality
spleen	UBERON:0002106	96.26	gold quality
nasal cavity epithelium	UBERON:0005384	96.21	gold quality
kidney	UBERON:0002113	96.19	gold quality
placenta	UBERON:0001987	96.13	gold quality
heart right ventricle	UBERON:0002080	96.08	gold quality
heart left ventricle	UBERON:0002084	96.05	gold quality
cardiac ventricle	UBERON:0002082	96.04	gold quality
caecum	UBERON:0001153	95.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.98	gold quality
nasal cavity mucosa	UBERON:0001826	95.95	gold quality
epithelial cell of pancreas	CL:0000083	95.89	gold quality
vermiform appendix	UBERON:0001154	95.89	gold quality
bone marrow	UBERON:0002371	95.89	gold quality
germinal epithelium of ovary	UBERON:0001304	95.85	gold quality
skeletal muscle tissue	UBERON:0001134	95.81	gold quality
tongue	UBERON:0001723	95.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.81	gold quality
pancreas	UBERON:0001264	95.80	gold quality
ganglionic eminence	UBERON:0004023	95.77	gold quality
synovial joint	UBERON:0002217	95.75	gold quality
lower lobe of lung	UBERON:0008949	95.75	gold quality
transverse colon	UBERON:0001157	95.73	gold quality
muscle of leg	UBERON:0001383	95.69	gold quality
pylorus	UBERON:0001166	95.63	gold quality
muscle tissue	UBERON:0002385	95.59	gold quality
oral cavity	UBERON:0000167	95.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.49	gold quality
gastrocnemius	UBERON:0001388	95.43	gold quality
superior surface of tongue	UBERON:0007371	95.42	gold quality
heart	UBERON:0000948	95.29	gold quality
gall bladder	UBERON:0002110	95.29	gold quality
endometrium	UBERON:0001295	95.22	gold quality
penis	UBERON:0000989	95.21	gold quality
small intestine	UBERON:0002108	95.21	gold quality
prostate gland	UBERON:0002367	95.18	gold quality
tibia	UBERON:0000979	95.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.14	gold quality
cardiac atrium	UBERON:0002081	95.02	gold quality
right atrium auricular region	UBERON:0006631	94.90	gold quality
spinal cord	UBERON:0002240	94.87	gold quality
parietal pleura	UBERON:0002400	94.84	gold quality
body of stomach	UBERON:0001161	94.83	gold quality
intestine	UBERON:0000160	94.73	gold quality
bronchial epithelial cell	CL:0002328	94.58	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.58	gold quality
large intestine	UBERON:0000059	94.52	gold quality
cardia of stomach	UBERON:0001162	94.46	gold quality
apex of heart	UBERON:0002098	94.45	gold quality
bronchus	UBERON:0002185	94.44	gold quality
epithelium of mammary gland	UBERON:0003244	94.39	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-81383	no	283.68
E-MTAB-5061	no	3.22
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	245.2	low
Skeletal muscle	tissue	117.7	medium
Duodenum	tissue	101.4	medium
Lymph node	tissue	98.3	not detected
Tongue	tissue	90.9
Small intestine	tissue	81.7	medium
Colon	tissue	77.5	medium
Kidney	tissue	75.8	medium
Thyroid gland	tissue	75.0	medium
Heart muscle	tissue	73.0	low
Parathyroid gland	tissue	70.8	medium
Bone marrow	tissue	66.7	not detected
Stomach 1	tissue	64.8	high
Rectum	tissue	64.2	medium
Tonsil	tissue	62.6	not detected
Placenta	tissue	61.5	medium
Corpus callosum	tissue	60.9
Choroid plexus	tissue	57.3
Pancreas	tissue	56.3	medium
Thymus	tissue	56.2
Adrenal gland	tissue	55.2	medium
Appendix	tissue	50.6	medium
Spinal cord	tissue	49.9
Spleen	tissue	49.7	not detected
Midbrain	tissue	47.0
Medulla oblongata	tissue	46.4
Thalamus	tissue	46.2
Breast	tissue	45.4	medium
Pons	tissue	44.3
Substantia nigra	tissue	44.2
Urinary bladder	tissue	43.3	low
Putamen	tissue	41.7
Salivary gland	tissue	41.4	medium
Lung	tissue	40.9	medium
Superior colliculi	tissue	40.8
Gallbladder	tissue	40.3	medium
Epididymis	tissue	38.8	low
Periaqueductal gray	tissue	38.2
Caudate putamen	tissue	37.6
Prostate	tissue	36.7	not detected
Frontal cortex	tissue	35.9
Septum	tissue	35.0
Ventral forebrain	tissue	34.9
Hypothalamus	tissue	34.3
Hippocampal formation	tissue	30.4
Fallopian tube	tissue	30.2	medium
Cervix	tissue	29.6	medium
Basal ganglia	tissue	28.5	low
Esophagus	tissue	28.0	low
Cerebral cortex	tissue	27.2	medium
Somatosensory cortex	tissue	27.2
Motor cortex	tissue	27.1
Ovary	tissue	26.8	not detected
Occipital cortex	tissue	26.6
Adipose tissue	tissue	26.1	low
Amygdala	tissue	26.1
Pituitary gland	tissue	26.0
Seminal vesicle	tissue	25.3	low
Retrosplenial cortex	tissue	24.4
Olfactory bulb	tissue	24.3

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (60.9), Ventral spinal cord (49.9), Dorsal spinal cord (44.8), Corpus callosum, splenium (white matter) (40.8), Lateral funiculus (white matter) (37.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CIAO2A by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 42 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-4711-5P	98.89	68.00	965
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-501-5P	98.77	68.88	1328

Functional genomics

gnomAD constraint: pLI 0.0232, LOEUF 1.05, missense Z 0.127 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000300030 — one region, missense o/e 1.00. DepMap (CRISPR cell-line fitness): dependent in 21.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NCI-H1573 (-1.399), HCC-33 (-1.31), LN-340 (-1.148), HT-144_DAB_R (-1.123), JVE-015 (-1.065), SNU-620 (-1.05), SNU-1544 (-1.043), HT-144_DAB_ROX_R (-1.04), SUM-149PT (-1.03), KKU-100 (-1.021), HuNS1 (-1.016), Mero-14 (-1.01), JHUEM-1 (-1.004), C84 (-1.002), MUTZ-8 (-0.958).

Literature-anchored findings (GeneRIF, showing 5)

• putative metal-binding site of bacterial DUF59 proteins is not conserved in Fam96a, but Fam96a interacts tightly in vitro with Ciao1, the cytosolic iron-assembly protein (PMID:22683786)
• 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)
• FAM96A expression was much reduced in tumorigenic ICC-SCs. (PMID:25716227)
• our data suggest that hTERTR-FAM96A may serve as an efficient anti-tumor agent for the treatment of hepatocellular carcinoma. (PMID:28443470)
• FAM96A suppresses epithelial-mesenchymal transition and tumor metastasis by inhibiting TGFbeta1 signals. (PMID:35513087)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ciao2a	ENSDARG00000104940
mus_musculus	Ciao2a	ENSMUSG00000032381
rattus_norvegicus	Ciao2a	ENSRNOG00000017119
drosophila_melanogaster	galla-1	FBGN0034543

Paralogs (1): CIAO2B (ENSG00000166595)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915500) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased erythrocyte cell number	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
Caenorhabditis elegans	O62252	60.3%	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
DAPK2	protein-coding	23604
MIR422A	ncRNA	494334
SNX1	protein-coding	6642
HERC1	protein-coding	8925
CSNK1G1	protein-coding	53944
PPIB	protein-coding	5479
SNX22	protein-coding	79856
USP3-AS1	ncRNA	100130855
FBXL22	protein-coding	283807
PCLAF	protein-coding	9768

Protein

Protein identifiers

Cytosolic iron-sulfur assembly component 2A — Q9H5X1 (reviewed: Q9H5X1)

Alternative names: MIP18 family protein FAM96A

All UniProt accessions (4): Q9H5X1, A0AAQ5BII0, H0YKV4, H0YLH6

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 specifically matures ACO1 and stabilizes IREB2, connecting cytosolic iron-sulfur protein maturation with cellular iron regulation. May play a role in chromosome segregation through establishment of sister chromatid cohesion. May induce apoptosis in collaboration with APAF1.

Subunit / interactions. Monomer and homodimer. Component of the CIA complex. Interacts with CIAO1. Interacts with IREB2. Interacts with APAF1.

Subcellular location. Cytoplasm.

Tissue specificity. Substantially enriched in macrophages.

Similarity. Belongs to the MIP18 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H5X1-1	1	yes
Q9H5X1-2	2

RefSeq proteins (3): NP_001014812, NP_001276037, NP_115607* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF01883

UniProt features (23 total): binding site 8, helix 6, strand 6, chain 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
3UX2	Crystal Structure of Domain-Swapped Fam96a Major dimer	X-RAY DIFFRACTION	1.8
3UX3	Crystal Structure of Domain-Swapped Fam96a minor dimer	X-RAY DIFFRACTION	1.8
2M5H	NMR structure note: solution structure of monomeric human FAM96A	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H5X1-F1	86.90	0.69

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

Functional residue map

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

Ligand- & substrate-binding residues (8)

Position	Role
89	Zn(2+)
123	Zn(2+)
150	Zn(2+)
153	Zn(2+)

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 163 (showing top): MODULE_151, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, TGACCTY_ERR1_Q2, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_PROTEIN_MATURATION, GATA6_01, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, DODD_NASOPHARYNGEAL_CARCINOMA_UP, RYTTCCTG_ETS2_B, MODULE_568, MODULE_491, MODULE_114, AACATTC_MIR4093P, GOBP_CELL_CYCLE_PROCESS

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

GO Molecular Function (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytosolic [4Fe-4S] assembly targeting complex (GO:0097361)

GO top-level categories

12 GO namespaces:

Category	Terms
cellular anatomical structure	3
cell cycle process	1
metallo-sulfur cluster assembly	1
gene expression	1
protein metabolic process	1
cation binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	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) — 5 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
iron-sulfur cluster assembly	BP	direct assay
protein maturation	BP	mutant phenotype
cytosol	CC	direct assay
cytosolic [4Fe-4S] assembly targeting complex	CC	direct assay
nucleoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 622 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIAO2A	CIAO1	O76071	783
CIAO2A	MMS19	Q96T76	717
CIAO2A	CIAO3	Q9H6Q4	656
CIAO2A	NUBP1	P53384	605
CIAO2A	CIAPIN1	Q6FI81	572
CIAO2A	ABCB7	O75027	516
CIAO2A	GLRX3	O76003	504
CIAO2A	QNG1	Q5T6V5	481
CIAO2A	ISCA1	Q9BUE6	466
CIAO2A	CYB561	P49447	461
CIAO2A	FBXL5	Q9UKA1	453
CIAO2A	IREB2	P48200	430
CIAO2A	NDOR1	Q9UHB4	426
CIAO2A	SLC25A28	Q96A46	407
CIAO2A	SLC25A37	Q9NYZ2	405

IntAct

Human interaction partners of CIAO2A in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

25 partners by confidence:

Partner	Interaction type	MIscore	Records
CIAO1	physical association	0.950	17
TMED8	physical association	0.560	6
CREB3L1	physical association	0.560	5
APOA2	physical association	0.560	3
CMTM6	physical association	0.560	3
DERL1	physical association	0.560	3
DGAT2L6	physical association	0.560	3
EBAG9	physical association	0.560	3
ERGIC3	physical association	0.560	3
FKBP7	physical association	0.560	3
GJA8	physical association	0.560	3
GSC2	physical association	0.560	3
KCNIP1	physical association	0.560	3
LIME1	physical association	0.560	3
MEST	physical association	0.560	3
PLP2	physical association	0.560	3
PLPP6	physical association	0.560	3
PLPPR2	physical association	0.560	3
PRAF2	physical association	0.560	3
RHBDD2	physical association	0.560	3
SETD4	physical association	0.560	3
SIN3A	physical association	0.560	3
TNFRSF10D	physical association	0.560	3
VAMP3	physical association	0.560	3
MAP2K7	association	0.350	1

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CIAO2A	“form complex”	“CIAO1-CIAO2A-CIAO3 cytosolic iron-sulfur protein assembly complex”	binding

Disease & clinical

Genetic variants

Variant evidence for CIAO2A: 33 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

33 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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 36 predictions of 340):

Position(s)	Effect	Δscore	Sites
15:64075545	acceptor_gain	1.0000
15:64088685–64088686	donor_loss	1.0000	5
15:64093643–64093644	donor_loss	1.0000	4
15:64073029–64073030	acceptor_loss	0.9900	6
15:64075538–64075539	acceptor_loss	0.9900	5
15:64088852–64088853	acceptor_gain	0.9900	6
15:64093644	donor_loss	0.9900
15:64093663	donor_gain	0.9900
15:64073036	acceptor_loss	0.9800
15:64075490–64075491	donor_loss	0.9800	6

AlphaMissense

507 missense substitutions predicted likely pathogenic (of 1,027 scored), across 108 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
D135	8	1.000	1.000
D49	8	0.998	1.000
H123	8	0.995	0.999
N145	8	0.979	0.997
F83	8	0.954	0.999
H89	8	0.947	0.992
D42	8	0.891	0.967
D128	8	0.831	0.982
C90	7	0.999	1.000
E137	7	0.998	0.999
E51	7	0.994	0.998
E144	7	0.990	0.998
Q132	7	0.987	0.999
N134	7	0.976	0.996
K136	7	0.972	1.000
C155	7	0.964	0.997
I96	7	0.949	0.999
N130	7	0.942	0.997
C99	7	0.929	0.999
E57	7	0.887	0.987

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.59e-06
Prostate Adenocarcinoma (TCGA)	unfavorable	0.000925

Disease associations

OMIM: gene MIM:618382 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295943 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Cadmium	decreases expression	2
Cyclosporine	decreases expression	2
perfluorodecanesulfonic acid	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	decreases expression	1
perfluorobutanesulfonic acid	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	decreases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Rotenone	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	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
CHEMBL4118609	Binding	Binding affinity to FAM96A 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.