CIAPIN1

Summary

CIAPIN1 (cytokine induced apoptosis inhibitor 1, HGNC:28050) is a protein-coding gene on chromosome 16q21, encoding Anamorsin (Q6FI81). Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery required for the maturation of extramitochondrial Fe-S proteins. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

CIAPIN1 is a cytokine-induced inhibitor of apoptosis with no relation to apoptosis regulatory molecules of the BCL2 (MIM 151430) or CASP (see MIM 147678) families. Expression of CIAPIN1 is dependent on growth factor stimulation (Shibayama et al., 2004 [PubMed 14970183]).

Source: NCBI Gene 57019 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 53 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_020313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28050
Approved symbol	CIAPIN1
Name	cytokine induced apoptosis inhibitor 1
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	CIAE2
Ensembl gene	ENSG00000005194
Ensembl biotype	protein_coding
OMIM	608943
Entrez	57019

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 22 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000394391, ENST00000563341, ENST00000563561, ENST00000564885, ENST00000565368, ENST00000565786, ENST00000565961, ENST00000566284, ENST00000567518, ENST00000567751, ENST00000568940, ENST00000569246, ENST00000569370, ENST00000569979, ENST00000570000, ENST00000884886, ENST00000884887, ENST00000884888, ENST00000884889, ENST00000884890, ENST00000884891, ENST00000939127, ENST00000939128, ENST00000939129, ENST00000939130, ENST00000950773, ENST00000950774, ENST00000950775

RefSeq mRNA: 3 — MANE Select: NM_020313 NM_001308347, NM_001308358, NM_020313

CCDS: CCDS10781, CCDS76876, CCDS76877

Canonical transcript exons

ENST00000394391 — 9 exons

Exon	Start	End
ENSE00001426033	57440772	57440983
ENSE00001518383	57447342	57447385
ENSE00002609281	57428187	57429280
ENSE00003508172	57432487	57432560
ENSE00003540161	57431151	57431266
ENSE00003611026	57439182	57439334
ENSE00003634096	57434044	57434212
ENSE00003784459	57430258	57430339
ENSE00003786700	57436656	57436732

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.9090 / max 237.4867, expressed in 1807 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157529	22.9090	1807

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.91	gold quality
secondary oocyte	CL:0000655	98.91	gold quality
adult organism	UBERON:0007023	96.51	gold quality
left testis	UBERON:0004533	96.42	gold quality
right testis	UBERON:0004534	96.32	gold quality
testis	UBERON:0000473	95.18	gold quality
sperm	CL:0000019	94.30	gold quality
male germ cell	CL:0000015	94.14	gold quality
cortical plate	UBERON:0005343	93.96	gold quality
mucosa of transverse colon	UBERON:0004991	93.74	gold quality
esophagus squamous epithelium	UBERON:0006920	93.55	gold quality
right adrenal gland cortex	UBERON:0035827	93.52	gold quality
adrenal tissue	UBERON:0018303	93.44	gold quality
metanephros cortex	UBERON:0010533	93.33	gold quality
right adrenal gland	UBERON:0001233	93.16	gold quality
embryo	UBERON:0000922	93.13	gold quality
apex of heart	UBERON:0002098	93.11	gold quality
epithelium of esophagus	UBERON:0001976	93.08	gold quality
ganglionic eminence	UBERON:0004023	92.98	gold quality
islet of Langerhans	UBERON:0000006	92.90	gold quality
heart right ventricle	UBERON:0002080	92.90	gold quality
heart left ventricle	UBERON:0002084	92.86	gold quality
prefrontal cortex	UBERON:0000451	92.82	gold quality
cardiac ventricle	UBERON:0002082	92.78	gold quality
right atrium auricular region	UBERON:0006631	92.59	gold quality
left adrenal gland cortex	UBERON:0035825	92.55	gold quality
left adrenal gland	UBERON:0001234	92.54	gold quality
rectum	UBERON:0001052	92.53	gold quality
skin of leg	UBERON:0001511	92.43	gold quality
adrenal cortex	UBERON:0001235	92.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.33
E-CURD-112	no	3.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting CIAPIN1, 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-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-146A-3P	99.13	68.99	1881

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 30)

• it is concluded that CIAPIN1 confers multidrug resistance in gastric cancer cells, likely by upregulating MDR-1 and MRP-1 (PMID:16410721)
• CIAPIN1 was localized in both the cytoplasm and the nucleus and was accumulated in the nucleolus. Bioinformatic prediction disclosed a putative nuclear localization signal and a putative nuclear export signal within human CIAPIN1. (PMID:16957168)
• CIAPIN1 might be a DNA or RNA methyltransferase. (PMID:17935775)
• These findings suggest that downregulating CIAPIN1 could sensitize leukemia cells to chemotherapeutic drugs by downregulating MDR-1 and Bcl-2 and by upregulating Bax. (PMID:18059532)
• anamorsin expression in DLBCL patients with a low IPI was shown to be an unfavorable biomarker; anamorsin might play some roles in the abnormal growth of DLBCL. (PMID:18203020)
• CIAPIN1 is a suppressor of gastric cancer cell proliferation; CIAPIN1 might play an important role in the development of human gastric cancer. (PMID:18293492)
• Knock down of CIAPIN1 by adenovirus-delivered siRNA may be a potential therapeutic strategy for treatment of hepatocellular carcinoma in which CIAPIN1 is overexpressed. (PMID:18299278)
• correlation between CIAPIN1 down regulation and decreased MDR1 transcriptional activity were observed. (PMID:18389626)
• the CIAPIN1 genet could be used as a clinical marker to identify patients with CCRCC. (PMID:19081179)
• Results of immunohistochemical study showed that CIAPIN1 might play an important role in esophageal carcinogenesis, and it could be considered as a prognostic indicator in esophageal squamous cell carcinoma. (PMID:20411424)
• Low expression of CIAPIN1 is associated with colorectal cancer. (PMID:20815902)
• Anamorsin is a Mia40-dependent but ALR-independent IMS-protein and binds a [2Fe-2S] cluster before and after specific Mia40-driven Cys-oxidation. (PMID:21700214)
• Up-regulation of CIAPIN1 expression may play an important role in pathogenesis of leukemia. (PMID:21729524)
• In summary, our work revealed a novel function of CIAPIN1, which might possibly be used as an independent prognostic factor and a potential therapeutic target for pancreatic cancer (PMID:22677939)
• Elevated expression of nuclear CIAPIN1 negatively correlated with the survival of epithelial ovarian cancer patients (PMID:22713669)
• CIAPIN1 siRNA inhibited proliferation, migration and promotes apoptosis of vascular smooth muscle cells by regulating Bcl-2 and Bax. (PMID:23151078)
• the molecular basis of recognition between Ndor1 and anamorsin and of the electron transfer process, was investigated. (PMID:23596212)
• Mossbauer and EPR spectra of human anamorsin show that both the M1 motif and the M2 motif bind independently a [2Fe-2S] cluster through the four cysteines of each motif. (PMID:23989406)
• The N-terminal methyltransferase-like domain of anamorsin probably functions as a structural scaffold to inhibit methyl transfers. (PMID:24123282)
• lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer and CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression. (PMID:24676475)
• the 25-kDa cleaved fragment of anamorsin was detected in post-mortem brains of Alzheimer and Parkinson disease patients (PMID:24973211)
• CIAPIN1 targeted NHE1 to mediate differentiation of K562 cells via ERK1/2 pathway. (PMID:25043809)
• CIAPIN1 over-expression decreases NHE1 expression and ERK1/2 phosphorylation. (PMID:25724898)
• CIAPIN1 and ABCA13 may be novel markers of poor outcome in pre-chemotherapy serous carcinoma effusions. (PMID:25889687)
• results of the present study suggest that downregulation of the CIAPIN1 gene in multiple myeloma cells may be associated with the development of this disease. (PMID:25901506)
• the effects of CIAPIN-1 in chondrocytes, focusing on extracellular signal-regulated kinase (ERK)-1/2 and p38 kinase signaling (PMID:27644154)
• The [2Fe-2S] clusters of mitoNEET are reduced via the formation of a transient complex that brings the [2Fe-2S] clusters of mitoNEET close to the redox-active [2Fe-2S] cluster of anamorsin. (PMID:28648056)
• High CIAPIN1 expression is correlated with Non-small Cell Lung Cancer. (PMID:30637589)
• NHE1 (Na+/H+ exchanger 1) expression and ERK1/2 phosphorylation decreased along with CIAPIN1 upregulation. (PMID:31093311)
• Downregulation of CIAPIN1 regulates the proliferation, migration and glycolysis of breast cancer cells via inhibition of STAT3 pathway. (PMID:39242716)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ciapin1	ENSDARG00000045733
mus_musculus	Ciapin1	ENSMUSG00000031781
rattus_norvegicus	Ciapin1	ENSRNOG00000016234
drosophila_melanogaster	CIAPIN1	FBGN0001977
caenorhabditis_elegans		WBGENE00020604

Protein

Protein identifiers

Anamorsin — Q6FI81 (reviewed: Q6FI81)

Alternative names: Cytokine-induced apoptosis inhibitor 1, Fe-S cluster assembly protein DRE2 homolog

All UniProt accessions (8): Q6FI81, H3BPG7, H3BQ23, H3BT65, H3BTT4, H3BTZ8, H3BUG4, H3BV90

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery required for the maturation of extramitochondrial Fe-S proteins. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis, facilitating the de novo assembly of a [4Fe-4S] cluster on the scaffold complex NUBP1-NUBP2. Electrons are transferred to CIAPIN1 from NADPH via the FAD- and FMN-containing protein NDOR1. NDOR1-CIAPIN1 are also required for the assembly of the diferric tyrosyl radical cofactor of ribonucleotide reductase (RNR), probably by providing electrons for reduction during radical cofactor maturation in the catalytic small subunit. Has anti-apoptotic effects in the cell. Involved in negative control of cell death upon cytokine withdrawal. Promotes development of hematopoietic cells.

Subunit / interactions. Monomer. Interacts with NDOR1; its oxidized form can be reduced by NDOR1. Interacts with CHCHD4 and may be a substrate for CHCHD4 chaperone activity.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion intermembrane space.

Tissue specificity. Ubiquitously expressed. Highly expressed in heart, liver and pancreas.

Cofactor. In the presence of oxygen, the A site-bound [2Fe-2S] cluster is labile and the B site-bound [4Fe-4S] cluster is readily converted into a [2Fe-2S] cluster, a reason why recombinant protein is often isolated with a single [2Fe-2S] cluster.

Domain organisation. The twin Cx2C motifs are involved in the recognition by the mitochondrial CHCHD4/MIA40-GFER/ERV1 disulfide relay system. The formation of 2 disulfide bonds in the Cx2C motifs through dithiol/disulfide exchange reactions effectively traps the protein in the mitochondrial intermembrane space. The C-terminal domain binds 2 Fe-S clusters but is otherwise mostly in an intrinsically disordered conformation. The N-terminal domain has structural similarity with S-adenosyl-L-methionine-dependent methyltransferases, but does not bind S-adenosyl-L-methionine. It is required for correct assembly of the 2 Fe-S clusters.

Miscellaneous. ‘Ana-mors-in’ means ‘anti-death molecule’ in Latin.

Similarity. Belongs to the anamorsin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6FI81-1	1	yes
Q6FI81-2	2
Q6FI81-3	3

RefSeq proteins (3): NP_001295276, NP_001295287, NP_064709* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007785	Anamorsin	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR046408	CIAPIN1	Domain
IPR049011	Anamorsin_N_metazoan	Domain

Pfam: PF05093, PF20922

UniProt features (47 total): binding site 8, modified residue 8, strand 8, helix 7, region of interest 4, sequence conflict 4, splice variant 2, sequence variant 2, short sequence motif 2, chain 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4M7R	X-RAY DIFFRACTION	1.8
2LD4	SOLUTION NMR
2YUI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6FI81-F1	80.45	0.41

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): 251; 274; 277; 285; 288; 237; 246; 249

Post-translational modifications (8): 136, 177, 182, 183, 215, 272, 305, 307

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 138 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, WANG_RESPONSE_TO_BEXAROTENE_UP, GOCC_MITOCHONDRIAL_ENVELOPE, chr16q21, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GCM_NF2, MODULE_18, ACEVEDO_LIVER_CANCER_UP, WANG_PROSTATE_CANCER_ANDROGEN_INDEPENDENT, GOCC_ORGANELLE_ENVELOPE_LUMEN, GOCC_NUCLEOLUS, MODULE_13, ROYLANCE_BREAST_CANCER_16Q_COPY_NUMBER_UP, STEIN_ESRRA_TARGETS_UP, GOMF_METAL_CLUSTER_BINDING

GO Biological Process (4): apoptotic process (GO:0006915), iron-sulfur cluster assembly (GO:0016226), hemopoiesis (GO:0030097), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (7): iron ion binding (GO:0005506), electron transfer activity (GO:0009055), 2 iron, 2 sulfur cluster binding (GO:0051537), 4 iron, 4 sulfur cluster binding (GO:0051539), protein binding (GO:0005515), metal ion binding (GO:0046872), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (6): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), nucleus (GO:0005634)

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
iron-sulfur cluster binding	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
metallo-sulfur cluster assembly	1
cell development	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
transition metal ion binding	1
molecular_function	1
binding	1
cation binding	1
metal cluster binding	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
mitochondrial envelope	1
organelle envelope lumen	1

Protein interactions and networks

STRING

1042 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIAPIN1	NDOR1	Q9UHB4	964
CIAPIN1	NUBP1	P53384	907
CIAPIN1	CIAO3	Q9H6Q4	889
CIAPIN1	GLRX3	O76003	807
CIAPIN1	MMS19	Q96T76	795
CIAPIN1	CIAO1	O76071	793
CIAPIN1	NFS1	Q9Y697	719
CIAPIN1	CIAO2B	Q9Y3D0	718
CIAPIN1	BOLA2	Q9H3K6	717
CIAPIN1	LYRM4	Q9HD34	709
CIAPIN1	KLHL24	Q6TFL4	694
CIAPIN1	ZNF428	Q96B54	687
CIAPIN1	NFU1	Q9UMS0	679
CIAPIN1	IBA57	Q5T440	666
CIAPIN1	BOLA1	Q9Y3E2	666

IntAct

93 interactions, top by confidence:

A	B	Type	Score
CIAPIN1	GLRX3	psi-mi:“MI:0915”(physical association)	0.960
GLRX3	CIAPIN1	psi-mi:“MI:0915”(physical association)	0.960
CIAPIN1	GLRX3	psi-mi:“MI:0914”(association)	0.960
NDOR1	CIAPIN1	psi-mi:“MI:0915”(physical association)	0.890
CIAPIN1	NDOR1	psi-mi:“MI:0915”(physical association)	0.890

BioGRID (130): CIAPIN1 (Two-hybrid), CIAPIN1 (Two-hybrid), CIAPIN1 (Two-hybrid), CACNB3 (Affinity Capture-MS), GLRX3 (Affinity Capture-MS), NDOR1 (Affinity Capture-MS), BOLA1 (Affinity Capture-MS), CIAPIN1 (Two-hybrid), AARS (Co-fractionation), AIMP1 (Co-fractionation), AIMP2 (Co-fractionation), ATP6V1A (Co-fractionation), ATP6V1B2 (Co-fractionation), ATP6V1D (Co-fractionation), CUL2 (Co-fractionation)

ESM2 similar proteins: A1A5Z3, A1L2P7, A4QP75, A5PKL6, A6NNW6, A8QE76, A8Y3X9, B0BM20, B0WC25, B4FHF0, B5DG51, B5X5B4, B8BAI9, B9SEZ6, C3YEM5, P43896, P43897, Q05B89, Q13057, Q14CX7, Q17PI0, Q1RLX4, Q20819, Q3B8B2, Q3U2U7, Q4G069, Q4KLT3, Q4V7D6, Q503I8, Q5EA11, Q5U2Z5, Q5XF75, Q5XID1, Q6FI81, Q6ING2, Q6NTR1, Q6ZJS7, Q7SXA9, Q803A6, Q8BWZ3

Diamond homologs: A0BV78, A0CIS3, A1CQP0, A1D3K3, A2XYW4, A4H4W7, A4HT41, A4IHR0, A4RE46, A5K5K4, A6QXB4, A7A031, A7AWN0, A7S710, A7TT02, A8NWK4, A8X858, A9PBH9, A9S6X4, A9SUX2, A9V767, B0WQ75, B2B763, B2W1T4, B3L145, B3LRE5, B3MLC5, B3N5N3, B3RVZ1, B4GK79, B4HXL7, B4JAX0, B4KLC0, B4LRY2, B4NYT3, B4Q5Z1, B5XEX1, B6JVP0, B6TB21, B7FNA9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 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.

GO biological processes:

GO term	Partners	Fold	FDR
iron-sulfur cluster assembly	6	64.5×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	33
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4796703	GRCh38/hg38 16q21(chr16:57351323-58816575)x1	Likely pathogenic

SpliceAI

1438 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57432486:CCATG:C	donor_gain	1.0000
16:57432558:TCA:T	acceptor_gain	1.0000
16:57432559:CA:C	acceptor_gain	1.0000
16:57432559:CAC:C	acceptor_gain	1.0000
16:57432561:C:CC	acceptor_gain	1.0000
16:57432568:C:CT	acceptor_gain	1.0000
16:57432568:C:T	acceptor_gain	1.0000
16:57432569:A:T	acceptor_gain	1.0000
16:57432572:C:CT	acceptor_gain	1.0000
16:57432574:A:AC	acceptor_gain	1.0000
16:57432574:A:C	acceptor_gain	1.0000
16:57434038:CCTTA:C	donor_loss	1.0000
16:57434039:CTTA:C	donor_loss	1.0000
16:57434040:TTAC:T	donor_loss	1.0000
16:57434041:TA:T	donor_loss	1.0000
16:57434208:TGCAG:T	acceptor_gain	1.0000
16:57434209:GCAG:G	acceptor_gain	1.0000
16:57434210:CAG:C	acceptor_gain	1.0000
16:57434210:CAGC:C	acceptor_gain	1.0000
16:57434211:AGCTA:A	acceptor_loss	1.0000
16:57434213:C:CC	acceptor_gain	1.0000
16:57436733:C:CC	acceptor_gain	1.0000
16:57439185:CAG:C	donor_gain	1.0000
16:57440766:ACTT:A	donor_loss	1.0000
16:57440767:CTT:C	donor_loss	1.0000
16:57440768:TTACA:T	donor_loss	1.0000
16:57440769:TA:T	donor_loss	1.0000
16:57440770:A:AC	donor_gain	1.0000
16:57440770:AC:A	donor_loss	1.0000
16:57440771:C:CA	donor_gain	1.0000

AlphaMissense

2026 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57429260:G:C	F283L	1.000
16:57429260:G:T	F283L	1.000
16:57429262:A:G	F283L	1.000
16:57429221:G:C	F296L	0.999
16:57429221:G:T	F296L	0.999
16:57429223:A:G	F296L	0.999
16:57429247:A:G	C288R	0.999
16:57429255:C:G	C285S	0.999
16:57429256:A:T	C285S	0.999
16:57429259:G:T	R284S	0.999
16:57429222:A:G	F296S	0.998
16:57429246:C:G	C288S	0.998
16:57429246:C:T	C288Y	0.998
16:57429247:A:T	C288S	0.998
16:57429256:A:G	C285R	0.998
16:57429258:C:G	R284P	0.998
16:57429259:G:C	R284G	0.998
16:57429261:A:C	F283C	0.998
16:57429261:A:G	F283S	0.998
16:57429267:T:A	D281V	0.998
16:57429268:C:G	D281H	0.998
16:57429270:C:A	G280V	0.998
16:57429270:C:T	G280D	0.998
16:57429271:C:A	G280C	0.998
16:57429271:C:G	G280R	0.998
16:57429280:A:G	C277R	0.998
16:57429222:A:C	F296C	0.997
16:57429262:A:T	F283I	0.997
16:57429267:T:C	D281G	0.997
16:57430265:C:G	C274S	0.997

dbSNP variants (sampled 300 via entrez): RS1000369450 (16:57433737 G>A), RS1000474473 (16:57434620 A>G), RS1000700497 (16:57444389 C>T), RS1000831542 (16:57438498 A>G), RS1000903659 (16:57438799 A>G), RS1001079266 (16:57432801 A>G), RS1001133903 (16:57444656 C>T), RS1001533767 (16:57441159 T>A,C), RS1001566422 (16:57441385 A>C,G), RS1002432579 (16:57446022 T>G), RS1002767174 (16:57445847 T>G), RS1003210997 (16:57442473 C>T), RS1003231003 (16:57442674 T>C), RS1003338204 (16:57437022 G>A), RS1003470692 (16:57430590 A>G,T)

Disease associations

OMIM: gene MIM:608943 | disease phenotypes: MIM:619033

GenCC curated gene-disease

Mondo (1): Vissers-Bodmer syndrome (MONDO:0033618)

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 (2): CHEMBL4523341 (SINGLE PROTEIN), CHEMBL4742298 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.17	Kd	67.28	nM	CHEMBL3752910
7.17	ED50	67.28	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 18 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148072: Binding affinity to human CIAPIN1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0673	uM

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression	3
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	increases methylation, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
beauvericin	decreases expression	1
beta-methylcholine	affects expression	1
microcystin RR	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
abrine	increases expression	1
bisphenol AF	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases response to substance, increases secretion	1
Etoposide	decreases response to substance	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
Vincristine	decreases response to substance	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4358884	Binding	Inhibition of recombinant purified CIAPIN1 (unknown origin) assessed as accumulation of protein aggregates at 0.1 to 1.6 uM incubated for 1 to 6 hrs by size exclusion chromatography	Re-Evaluating the Mechanism of Action of α,β-Unsaturated Carbonyl DUB Inhibitors b-AP15 and VLX1570: A Paradigmatic Example of Unspecific Protein Cross-linking with Michael Acceptor Motif-Containing Drugs. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XC59	BHK-21 CIAPIN1+	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

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