CIART

Summary

CIART (circadian associated repressor of transcription, HGNC:25200) is a protein-coding gene on chromosome 1q21.2, encoding Circadian-associated transcriptional repressor (Q8N365). Transcriptional repressor which forms a negative regulatory component of the circadian clock and acts independently of the circadian transcriptional repressors: CRY1, CRY2 and BHLHE41.

Predicted to enable E-box binding activity. Predicted to be involved in circadian regulation of gene expression; locomotor rhythm; and negative regulation of DNA-templated transcription. Predicted to be located in PML body. Predicted to be active in nucleus.

Source: NCBI Gene 148523 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_144697

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25200
Approved symbol	CIART
Name	circadian associated repressor of transcription
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	BC017397, CHRONO
Ensembl gene	ENSG00000159208
Ensembl biotype	protein_coding
OMIM	615782
Entrez	148523

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000290363, ENST00000369094, ENST00000369095, ENST00000417398, ENST00000447007, ENST00000469255, ENST00000497211

RefSeq mRNA: 5 — MANE Select: NM_144697 NM_001300838, NM_001300839, NM_001300840, NM_001300841, NM_144697

CCDS: CCDS72906, CCDS949

Canonical transcript exons

ENST00000290363 — 5 exons

Exon	Start	End
ENSE00001044201	150283805	150283880
ENSE00001187300	150282554	150283633
ENSE00001418861	150286430	150287093
ENSE00003578505	150284597	150284708
ENSE00003648991	150284426	150284504

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 94.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1330 / max 98.7829, expressed in 1183 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5088	6.1330	1183

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.95	gold quality
mucosa of stomach	UBERON:0001199	93.94	gold quality
skin of abdomen	UBERON:0001416	90.92	gold quality
secondary oocyte	CL:0000655	90.76	gold quality
skin of leg	UBERON:0001511	90.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.30	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.44	gold quality
muscle of leg	UBERON:0001383	89.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.28	gold quality
caudate nucleus	UBERON:0001873	89.24	gold quality
lower esophagus	UBERON:0013473	89.19	gold quality
gastrocnemius	UBERON:0001388	89.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.56	gold quality
cerebellar hemisphere	UBERON:0002245	88.46	gold quality
cerebellar cortex	UBERON:0002129	88.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.28	gold quality
zone of skin	UBERON:0000014	88.26	gold quality
putamen	UBERON:0001874	87.82	gold quality
adenohypophysis	UBERON:0002196	87.56	gold quality
apex of heart	UBERON:0002098	87.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.95	gold quality
cerebellum	UBERON:0002037	86.94	gold quality
nucleus accumbens	UBERON:0001882	86.59	gold quality
tibial artery	UBERON:0007610	86.27	gold quality
popliteal artery	UBERON:0002250	86.20	gold quality
quadriceps femoris	UBERON:0001377	86.11	gold quality
vastus lateralis	UBERON:0001379	85.25	gold quality
right adrenal gland cortex	UBERON:0035827	84.91	gold quality
deltoid	UBERON:0001476	84.59	silver quality
right frontal lobe	UBERON:0002810	84.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8060	yes	368.62
E-ANND-3	yes	3.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, FOXC1

miRNA regulators (miRDB)

15 targeting CIART, 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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-331-5P	96.59	67.94	705

Literature-anchored findings (GeneRIF, showing 2)

• Study shows that:1- Chrono is a circadian clock gene whose transcription exhibits a robust circadian oscillation. 2- Is is a repressor of circadian transcriptional/translational feedback loops. 3- It may function to link epigenetic control mechanisms to stress responses. [review] (PMID:28010116)
• A multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection. (PMID:36918693)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ciarta	ENSDARG00000058094
mus_musculus	Ciart	ENSMUSG00000038550
rattus_norvegicus	Ciart	ENSRNOG00000042717

Protein

Protein identifiers

Circadian-associated transcriptional repressor — Q8N365 (reviewed: Q8N365)

Alternative names: ChIP-derived repressor of network oscillator, Computationally highlighted repressor of the network oscillator

All UniProt accessions (4): A0A1B0GX20, Q5TB12, Q5TB13, Q8N365

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor which forms a negative regulatory component of the circadian clock and acts independently of the circadian transcriptional repressors: CRY1, CRY2 and BHLHE41. In a histone deacetylase-dependent manner represses the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Abrogates the interaction of BMAL1 with the transcriptional coactivator CREBBP and can repress the histone acetyl-transferase activity of the CLOCK-BMAL1 heterodimer, reducing histone acetylation of its target genes. Rhythmically binds the E-box elements (5’-CACGTG-3’) on circadian gene promoters and its occupancy shows circadian oscillation antiphasic to BMAL1. Interacts with the glucocorticoid receptor (NR3C1) and contributes to the repressive function in the glucocorticoid response.

Subunit / interactions. Interacts with PER2, CRY2, BHLHE41, HDAC1 and NR3C1. Interacts with BMAL1.

Subcellular location. Nucleus. PML body.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N365-1	1	yes
Q8N365-2	2

RefSeq proteins (5): NP_001287767, NP_001287768, NP_001287769, NP_001287770, NP_653298* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031373	Ciart	Family

Pfam: PF15673

UniProt features (10 total): region of interest 3, compositionally biased region 3, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N365-F1	55.07	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): GOBP_CIRCADIAN_RHYTHM, BENPORATH_ES_WITH_H3K27ME3, WWTAAGGC_UNKNOWN, GOBP_BEHAVIOR, TGACCTY_ERR1_Q2, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GGGTGGRR_PAX4_03, USF_C, LYF1_01, GOBP_RHYTHMIC_BEHAVIOR, CREBP1_01, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, AR_01, chr1q21, GOCC_NUCLEAR_BODY

GO Biological Process (4): circadian regulation of gene expression (GO:0032922), locomotor rhythm (GO:0045475), negative regulation of DNA-templated transcription (GO:0045892), rhythmic process (GO:0048511)

GO Molecular Function (4): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), E-box binding (GO:0070888), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), PML body (GO:0016605)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
circadian rhythm	1
regulation of gene expression	1
locomotory behavior	1
circadian behavior	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
biological_process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear body	1

Protein interactions and networks

STRING

564 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIART	BMAL1	O00327	770
CIART	CRY2	Q49AN0	733
CIART	BHLHE41	Q9C0J9	720
CIART	PER3	P56645	714
CIART	PER2	O15055	667
CIART	NR1D2	Q14995	618
CIART	NR1D1	P20393	593
CIART	NPAS2	Q99743	585
CIART	TEF	Q10587	566
CIART	CRY1	Q16526	557
CIART	CIPC	Q9C0C6	530
CIART	CLOCK	O15516	517
CIART	NFIL3	Q16649	469
CIART	NPAS4	Q8IUM7	450
CIART	BMAL2	Q8WYA1	435

IntAct

28 interactions, top by confidence:

A	B	Type	Score
Bmal1	CIART	psi-mi:“MI:0915”(physical association)	0.610
Per2	CIART	psi-mi:“MI:0915”(physical association)	0.570
DAB1	CIART	psi-mi:“MI:0915”(physical association)	0.560
CIART	DAB1	psi-mi:“MI:0915”(physical association)	0.560
NFYC	CIART	psi-mi:“MI:0915”(physical association)	0.560
CASP6	CIART	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	CIART	psi-mi:“MI:0915”(physical association)	0.560
CIART	IGHA2	psi-mi:“MI:0914”(association)	0.530
Per2	NR1D1	psi-mi:“MI:0914”(association)	0.500
CIART	Per1	psi-mi:“MI:0915”(physical association)	0.400
CIART	Per3	psi-mi:“MI:0915”(physical association)	0.400
CIART	CLOCK	psi-mi:“MI:0914”(association)	0.350
CIART	OGT	psi-mi:“MI:0914”(association)	0.350
CIART	UQCRQ	psi-mi:“MI:0914”(association)	0.350
NFYC	CIART	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): CIART (Two-hybrid), TPM2 (Affinity Capture-MS), ZG16B (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), TPM2 (Affinity Capture-MS), OGT (Affinity Capture-MS), CIART (Affinity Capture-MS), CIART (Two-hybrid), ZG16B (Affinity Capture-MS), IGHA2 (Affinity Capture-MS), PNPT1 (Affinity Capture-MS), HIBCH (Affinity Capture-MS), BLVRA (Affinity Capture-MS), UQCRQ (Affinity Capture-MS)

ESM2 similar proteins: A0JNG6, A2AKB4, A7YWL5, B0BN13, O35181, O43734, O70142, O70240, O88286, O88566, P0DPB3, P0DPB4, P56975, P70298, P86174, P97303, Q00IB7, Q1LY51, Q2M3C6, Q2T9L4, Q3TY60, Q498S6, Q4V7B1, Q568Z1, Q5HZN9, Q5JTD0, Q5SYB0, Q5U5E5, Q5VT97, Q69ZB8, Q6PG95, Q6UXB0, Q6ZU67, Q76N89, Q80YE4, Q86XD5, Q8BWU3, Q8BZB3, Q8CD60, Q8N365

Diamond homologs: Q3TQ03, Q8N365

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

776 predictions. Top by Δscore:

Variant	Effect	Δscore
1:150282619:GT:G	donor_loss	1.0000
1:150283800:TACA:T	acceptor_loss	1.0000
1:150283802:CA:C	acceptor_loss	1.0000
1:150283803:A:AG	acceptor_gain	1.0000
1:150283803:AGT:A	acceptor_gain	1.0000
1:150283804:G:GT	acceptor_gain	1.0000
1:150283804:GT:G	acceptor_gain	1.0000
1:150283804:GTG:G	acceptor_gain	1.0000
1:150283804:GTGT:G	acceptor_gain	1.0000
1:150283804:GTGTA:G	acceptor_gain	1.0000
1:150283876:GAGAG:G	donor_gain	1.0000
1:150283877:AGAG:A	donor_loss	1.0000
1:150283878:GAG:G	donor_gain	1.0000
1:150283879:AGGT:A	donor_loss	1.0000
1:150283880:GG:G	donor_loss	1.0000
1:150283881:G:GA	donor_loss	1.0000
1:150283882:T:A	donor_loss	1.0000
1:150284421:CCCA:C	acceptor_loss	1.0000
1:150284422:CCA:C	acceptor_loss	1.0000
1:150284423:CAG:C	acceptor_loss	1.0000
1:150284424:A:AG	acceptor_gain	1.0000
1:150284424:AG:A	acceptor_gain	1.0000
1:150284424:AGG:A	acceptor_loss	1.0000
1:150284425:G:GT	acceptor_gain	1.0000
1:150284425:GG:G	acceptor_gain	1.0000
1:150284425:GGATT:G	acceptor_gain	1.0000
1:150284502:GGG:G	donor_gain	1.0000
1:150284503:GG:G	donor_gain	1.0000
1:150284503:GGG:G	donor_gain	1.0000
1:150284504:GG:G	donor_gain	1.0000

AlphaMissense

2494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:150284638:T:C	L188S	0.999
1:150283622:T:C	F119L	0.998
1:150283623:T:G	F119C	0.998
1:150283624:T:A	F119L	0.998
1:150283624:T:G	F119L	0.998
1:150283815:T:C	L126P	0.998
1:150284486:T:C	L168S	0.998
1:150284646:T:A	W191R	0.998
1:150284646:T:C	W191R	0.998
1:150283623:T:C	F119S	0.997
1:150283836:T:A	L133H	0.997
1:150284649:T:C	F192L	0.997
1:150284651:T:A	F192L	0.997
1:150284651:T:G	F192L	0.997
1:150283823:T:C	F129L	0.996
1:150283825:T:A	F129L	0.996
1:150283825:T:G	F129L	0.996
1:150284429:T:C	L149S	0.996
1:150284463:G:C	R160S	0.996
1:150284463:G:T	R160S	0.996
1:150284470:C:A	R163S	0.996
1:150284471:G:C	R163P	0.996
1:150284648:G:C	W191C	0.996
1:150284648:G:T	W191C	0.996
1:150283633:G:C	K122N	0.995
1:150283633:G:T	K122N	0.995
1:150284438:T:C	F152S	0.995
1:150284462:G:T	R160M	0.995
1:150284465:T:C	I161T	0.995
1:150284465:T:G	I161S	0.995

dbSNP variants (sampled 300 via entrez): RS1001638670 (1:150285633 C>A), RS1002646866 (1:150284168 C>A), RS1003875642 (1:150286963 A>C,T), RS1003905232 (1:150287325 G>A,C,T), RS1004493200 (1:150281127 C>A), RS1004876676 (1:150285382 A>G), RS1008438126 (1:150282369 C>T), RS1008453744 (1:150281942 G>A,C), RS1010416062 (1:150285007 T>C), RS1011724282 (1:150281877 A>G,T), RS1012219151 (1:150282533 C>T), RS1012292671 (1:150282781 A>G), RS1013225997 (1:150281256 A>T), RS1013294795 (1:150281503 G>C), RS1014081510 (1:150285668 G>A)

Disease associations

OMIM: gene MIM:615782 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST002539_32	Schizophrenia	4.000000e-10
GCST003184_1	Atopic dermatitis	5.000000e-09
GCST003184_11	Atopic dermatitis	1.000000e-07
GCST008103_32	Bipolar disorder	5.000000e-08
GCST010204_30	Low density lipoprotein cholesterol levels	3.000000e-08
GCST010696_11	Cortical thickness (min-P)	2.000000e-23
GCST010697_17	Cortical surface area (min-P)	9.000000e-09
GCST010698_23	Subcortical volume (min-P)	2.000000e-08
GCST010699_48	Brain morphology (min-P)	3.000000e-08
GCST010700_28	Cortical thickness (MOSTest)	8.000000e-38
GCST010701_113	Cortical surface area (MOSTest)	9.000000e-12
GCST010702_126	Subcortical volume (MOSTest)	4.000000e-09
GCST010703_244	Brain morphology (MOSTest)	9.000000e-12
GCST90000582_5	Spontaneous coronary artery dissection	2.000000e-12
GCST90000583_1	Spontaneous coronary artery dissection	1.000000e-11
GCST90002404_474	Red cell distribution width	2.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	7
arsenite	affects binding, increases reaction, increases methylation	2
Benzo(a)pyrene	affects methylation, increases expression	2
sotorasib	decreases expression, affects cotreatment	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
ferrous chloride	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases expression	1
trametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Cadmium	decreases expression	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Lead	decreases expression	1
Manganese	increases expression, increases abundance	1
Oxygen	increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1

Clinical trials (associated diseases)

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