# CIAO2A > Gene · canonical: https://sugi.bio/atlas/gene/CIAO2A/ > Atlas v1.12.2 · generated 2026-10-13T13:32:47+00:00 ## 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](https://www.ncbi.nlm.nih.gov/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](https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-81383) | no | 283.68 | | [E-MTAB-5061](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-5061) | no | 3.22 | | [E-ANND-3](https://www.ebi.ac.uk/gxa/sc/experiments/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](https://gnomad.broadinstitute.org/) **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](https://www.informatics.jax.org/marker/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](https://www.uniprot.org/uniprotkb/Q3T0U7/entry) | 96.9% | Diamond | | Schizosaccharomyces pombe 972h- | [Q9UTL0](https://www.uniprot.org/uniprotkb/Q9UTL0/entry) | 61.2% | Diamond | | Dictyostelium discoideum | [Q54QK1](https://www.uniprot.org/uniprotkb/Q54QK1/entry) | 60.9% | Diamond | | Arabidopsis thaliana | [Q9C9G6](https://www.uniprot.org/uniprotkb/Q9C9G6/entry) | 60.5% | Diamond | | Caenorhabditis elegans | [O62252](https://www.uniprot.org/uniprotkb/O62252/entry) | 60.3% | Diamond | | Saccharomyces cerevisiae S288C | [P38829](https://www.uniprot.org/uniprotkb/P38829/entry) | 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](/atlas/gene/DAPK2/) | protein-coding | 23604 | | [MIR422A](/atlas/gene/MIR422A/) | ncRNA | 494334 | | [SNX1](/atlas/gene/SNX1/) | protein-coding | 6642 | | [HERC1](/atlas/gene/HERC1/) | protein-coding | 8925 | | [CSNK1G1](/atlas/gene/CSNK1G1/) | protein-coding | 53944 | | [PPIB](/atlas/gene/PPIB/) | protein-coding | 5479 | | [SNX22](/atlas/gene/SNX22/) | protein-coding | 79856 | | [USP3-AS1](/atlas/gene/USP3-AS1/) | ncRNA | 100130855 | | [FBXL22](/atlas/gene/FBXL22/) | protein-coding | 283807 | | [PCLAF](/atlas/gene/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 →](https://www.uniprot.org/uniprotkb/Q9H5X1/entry) **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](https://amigo.geneontology.org/amigo/term/GO:0016226) | BP | direct assay | | [protein maturation](https://amigo.geneontology.org/amigo/term/GO:0051604) | BP | mutant phenotype | | [cytosol](https://amigo.geneontology.org/amigo/term/GO:0005829) | CC | direct assay | | [cytosolic [4Fe-4S] assembly targeting complex](https://amigo.geneontology.org/amigo/term/GO:0097361) | CC | direct assay | | [nucleoplasm](https://amigo.geneontology.org/amigo/term/GO:0005654) | 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](#clinvar) (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. ## Related Atlas pages *No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.*