CCAR1

Summary

CCAR1 (cell division cycle and apoptosis regulator 1, HGNC:24236) is a protein-coding gene on chromosome 10q21.3, encoding Cell division cycle and apoptosis regulator protein 1 (Q8IX12). Associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. It is a selective cancer dependency (DepMap: 77.3% of cell lines).

Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; transcription coactivator activity; and transcription corepressor activity. Involved in positive regulation of cell migration and positive regulation of cell population proliferation. Acts upstream of or within positive regulation of apoptotic process. Located in nuclear envelope lumen.

Source: NCBI Gene 55749 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 120 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 77.3% of screened cell lines
• MANE Select transcript: NM_018237

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24236
Approved symbol	CCAR1
Name	cell division cycle and apoptosis regulator 1
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	CARP1, CARP-1, uc.285+, FLJ10590
Ensembl gene	ENSG00000060339
Ensembl biotype	protein_coding
OMIM	612569
Entrez	55749

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 29 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000265872, ENST00000398676, ENST00000479143, ENST00000480627, ENST00000483264, ENST00000494903, ENST00000536012, ENST00000536391, ENST00000538031, ENST00000539250, ENST00000539539, ENST00000540210, ENST00000541012, ENST00000543225, ENST00000543229, ENST00000543706, ENST00000543719, ENST00000630771, ENST00000859847, ENST00000928521, ENST00000928522, ENST00000928523, ENST00000928524, ENST00000928525, ENST00000928526, ENST00000928527, ENST00000928528, ENST00000928529, ENST00000928530, ENST00000928531, ENST00000928532, ENST00000928533, ENST00000928534, ENST00000928535, ENST00000928536, ENST00000928537, ENST00000958483

RefSeq mRNA: 3 — MANE Select: NM_018237 NM_001282959, NM_001282960, NM_018237

CCDS: CCDS60547, CCDS7282

Canonical transcript exons

ENST00000265872 — 25 exons

Exon	Start	End
ENSE00000933674	68737845	68737889
ENSE00001461089	68791207	68792377
ENSE00002285870	68721239	68721282
ENSE00003458781	68749136	68749265
ENSE00003482917	68756273	68756483
ENSE00003483451	68789710	68789915
ENSE00003491619	68765888	68766079
ENSE00003494439	68755370	68755536
ENSE00003495982	68771206	68771445
ENSE00003504568	68754714	68754827
ENSE00003517468	68749524	68749685
ENSE00003520241	68747374	68747566
ENSE00003535715	68788143	68788328
ENSE00003548811	68742376	68742569
ENSE00003575408	68722455	68722577
ENSE00003584651	68761007	68761192
ENSE00003590510	68772988	68773099
ENSE00003601208	68740629	68740661
ENSE00003621826	68753852	68754077
ENSE00003650549	68736876	68737048
ENSE00003667816	68786136	68786218
ENSE00003677469	68747161	68747275
ENSE00003690208	68757294	68757377
ENSE00003691762	68786546	68786692
ENSE00003784028	68787927	68788047

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.7633 / max 582.3304, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105257	61.2141	1823
105258	1.5612	635
105259	0.4649	232
105260	0.3612	136
105256	0.1618	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.89	gold quality
pancreatic ductal cell	CL:0002079	98.77	gold quality
visceral pleura	UBERON:0002401	98.69	gold quality
parietal pleura	UBERON:0002400	97.90	gold quality
ventricular zone	UBERON:0003053	97.85	gold quality
sural nerve	UBERON:0015488	97.78	gold quality
pylorus	UBERON:0001166	97.57	gold quality
calcaneal tendon	UBERON:0003701	97.30	gold quality
seminal vesicle	UBERON:0000998	97.27	gold quality
cardia of stomach	UBERON:0001162	97.27	gold quality
ganglionic eminence	UBERON:0004023	97.27	gold quality
oviduct epithelium	UBERON:0004804	97.26	gold quality
kidney epithelium	UBERON:0004819	97.14	gold quality
tendon	UBERON:0000043	96.92	gold quality
tonsil	UBERON:0002372	96.80	gold quality
renal medulla	UBERON:0000362	96.73	gold quality
mucosa of stomach	UBERON:0001199	96.70	gold quality
colonic epithelium	UBERON:0000397	96.69	gold quality
secondary oocyte	CL:0000655	96.62	gold quality
left ovary	UBERON:0002119	96.58	gold quality
cortical plate	UBERON:0005343	96.52	gold quality
adrenal tissue	UBERON:0018303	96.49	gold quality
metanephros cortex	UBERON:0010533	96.45	gold quality
germinal epithelium of ovary	UBERON:0001304	96.43	gold quality
right ovary	UBERON:0002118	96.43	gold quality
primary visual cortex	UBERON:0002436	96.43	gold quality
tibia	UBERON:0000979	96.37	gold quality
medial globus pallidus	UBERON:0002477	96.35	gold quality
ovary	UBERON:0000992	96.34	gold quality
tendon of biceps brachii	UBERON:0008188	96.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6524	no	230.91
E-MTAB-10596	no	223.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, THAP1

miRNA regulators (miRDB)

88 targeting CCAR1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
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-4425	100.00	67.59	1049
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-579-3P	99.86	71.66	3628

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 77.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 25)

• cell cycle and apoptosis regulatory protein-1 is a novel mediator of apoptosis signaling by retinoid CD437 (PMID:12816952)
• The study shows that tyrosine 192 of CARP-1 is a target of apoptosis signaling, and CARP-1, in turn, promotes apoptosis by activating p38 MAPK and caspase-9. (PMID:16543231)
• CARP-1 is a suppressor of breast cancer growth, and its expression is diminished in tumors, in part, by methylation-dependent silencing (PMID:17513614)
• Damaging exercise induced the expression of capZalpha, MCIP1, CARP1, DNAJB2, c-myc, and junD, each of which are likely involved in skeletal muscle growth, remodeling, and stress management. (PMID:18321953)
• CCAR1 regulates expression of key proliferation-inducing genes. (PMID:18722177)
• These results provide the first evidence for the microtubule dependent association of AKAP350A and CCAR1 with RNA stress granules. (PMID:19073175)
• CCAR1 is a novel component of Wnt/beta-catenin signaling that plays an important role in transcriptional regulation by beta-catenin. (PMID:19520846)
• anaphase-promoting complex (APC)-2-cell cycle and apoptosis regulatory protein (CARP)-1 interaction antagonists are novel regulators of cell growth and apoptosis (PMID:21903591)
• CCAR1 is a novel partner of Ngn3 in mediating endocrine differentiation. (PMID:22266316)
• necdin exerts its pro-survival activity by counteracting the action of the pro-apoptotic protein Cell Cycle Apoptosis Regulatory Protein (CCAR1/CARP1) (PMID:22905258)
• Par-4/THAP1 complex and Notch3 competitively regulated pre-mRNA splicing of CCAR1 and affected inversely the survival of T-cell acute lymphoblastic leukemia cells. (PMID:23975424)
• this study provides insight into the structure and evolution of DBC1 and CCAR1, which may impact future studies on the biological functions of these proteins. (PMID:25610865)
• High CCAR1 expression tended to be an independent predictor of shorter recurrence-free survival in hepatocellular carcinoma patients after curative hepatectomy. (PMID:26511806)
• Our data demonstrates that CCAR1 contributes to carcinogenesis in gastric cancer and is required for the survival of gastric cancer cells. Moreover, CCAR1 may serve as a diagnostic marker and a potential therapeutic target. (PMID:28230774)
• CCAR1 to be a novel transcriptional cofactor for CAR. (PMID:30397001)
• The results revealed that ZKSCAN1 circular RNA exerted its inhibitive role by competitively binding FMRP, therefore, block the binding between FMRP and beta-catenin-binding protein-cell cycle and apoptosis regulator 1 (CCAR1) mRNA, and subsequently restrain the transcriptional activity of Wnt signaling. (PMID:31281495)
• Antagonizing binding of cell cycle and apoptosis regulatory protein 1 (CARP-1) to the NEMO/IKKgamma protein enhances the anticancer effect of chemotherapy. (PMID:32024692)
• MiR-122-5p increases radiosensitivity and aggravates radiation-induced rectal injury through CCAR1. (PMID:32422326)
• RP11284F21.9 promotes lung carcinoma proliferation and invasion via the regulation of miR6273p/CCAR1. (PMID:32945522)
• Immune responses to CCAR1 and other dermatomyositis autoantigens are associated with attenuated cancer emergence. (PMID:35040440)
• Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma. (PMID:36932387)
• m6A-modified circABCC4 promotes stemness and metastasis of prostate cancer by recruiting IGF2BP2 to increase stability of CCAR1. (PMID:37563361)
• A transcribed ultraconserved noncoding RNA, uc.285+, promotes colorectal cancer proliferation through dual targeting of CDC42 by directly binding mRNA and protein. (PMID:38552953)
• The splicing factor CCAR1 regulates the Fanconi anemia/BRCA pathway. (PMID:39025073)
• RUNX1-PDIA5 Axis Promotes Malignant Progression of Glioblastoma by Regulating CCAR1 Protein Expression. (PMID:39247813)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccar1	ENSDARG00000074759
mus_musculus	Ccar1	ENSMUSG00000020074
rattus_norvegicus	Ccar1	ENSRNOG00000000397
caenorhabditis_elegans		WBGENE00003085

Paralogs (1): CCAR2 (ENSG00000158941)

Protein

Protein identifiers

Cell division cycle and apoptosis regulator protein 1 — Q8IX12 (reviewed: Q8IX12)

Alternative names: Cell cycle and apoptosis regulatory protein 1, Death inducer with SAP domain

All UniProt accessions (11): Q8IX12, A0A0C4DGG8, F5H1H2, F5H1L3, F5H2E6, F5H3E1, F5H3I8, F5H7M9, F5H808, H0YFJ7, H0YFT7

UniProt curated annotations — full annotation on UniProt →

Function. Associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Recruited to endogenous nuclear receptor target genes in response to the appropriate hormone. Also functions as a p53 coactivator. May thus play an important role in transcriptional regulation. May be involved in apoptosis signaling in the presence of the reinoid CD437. Apoptosis induction involves sequestration of 14-3-3 protein(s) and mediated altered expression of multiple cell cycle regulatory genes including MYC, CCNB1 and CDKN1A. Plays a role in cell cycle progression and/or cell proliferation. In association with CALCOCO1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells. Can act as a both a coactivator and corepressor of AR-mediated transcription. Contributes to chromatin looping and AR transcription complex assembly by stabilizing AR-GATA2 association on chromatin and facilitating MED1 and RNA polymerase II recruitment to AR-binding sites. May play an important role in the growth and tumorigenesis of prostate cancer cells.

Subunit / interactions. Directly interacts with ESR1, NR3C1 and p53/TP53. Interacts (via N-terminus) with CALCOCO1. Interacts with MED1. Interacts with GATA1. Interacts with AR and GATA2.

Subcellular location. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed in various epithelial cancer cell lines, including breast, colon, prostate, pancreatic and leukemia. Expression is regulated by growth factors.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IX12-1	1	yes
Q8IX12-2	2

RefSeq proteins (3): NP_001269888, NP_001269889, NP_060707* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003034	SAP_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR025223	S1-like_RNA-bd_dom	Domain
IPR025224	CCAR1/CCAR2	Family
IPR025954	DBC1/CARP1_inactive_NUDIX	Domain
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR045353	LAIKA	Domain

Pfam: PF02037, PF14443, PF14444, PF19256

UniProt features (48 total): compositionally biased region 10, sequence conflict 10, region of interest 8, modified residue 6, cross-link 5, sequence variant 4, coiled-coil region 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IX12-F1	69.55	0.38

Functional residue map

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

Post-translational modifications (11): 456, 627, 667, 685, 697, 861, 637, 1012, 1012, 1067, 1135

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 163 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, chr10q21, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, REACTOME_MRNA_3_END_PROCESSING, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, USF_01, WTGAAAT_UNKNOWN, GGCKCATGS_UNKNOWN, GARY_CD5_TARGETS_DN, REACTOME_MRNA_SPLICING, DODD_NASOPHARYNGEAL_CARCINOMA_UP, ATCATGA_MIR433, USF_02, WHN_B

GO Biological Process (9): ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), positive regulation of cell population proliferation (GO:0008284), protein ubiquitination (GO:0016567), positive regulation of cell migration (GO:0030335), positive regulation of apoptotic process (GO:0043065), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nuclear envelope lumen (GO:0005641), nucleoplasm (GO:0005654), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Dengue Virus Infection	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription coregulator activity	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
protein modification by small protein conjugation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
positive regulation of DNA-templated transcription	1
negative regulation of DNA-templated transcription	1
nucleic acid binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear envelope	1
organelle envelope lumen	1
nuclear lumen	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCAR1	FMR1	Q06787	741
CCAR1	RARG	P13631	647
CCAR1	CCNB1	P14635	643
CCAR1	CDKN3	Q16667	605
CCAR1	PABPC1	P11940	598
CCAR1	CAPRIN1	Q14444	540
CCAR1	FXR1	P51114	538
CCAR1	FXR2	P51116	533
CCAR1	G3BP1	Q13283	533
CCAR1	DEDD2	Q8WXF8	511
CCAR1	STOX1	Q6ZVD7	507
CCAR1	DDX50	Q9BQ39	503
CCAR1	ESR1	P03372	493
CCAR1	FADD	Q13158	482
CCAR1	SRSF11	Q05519	471

IntAct

149 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
ARFIP2	ARFIP1	psi-mi:“MI:0914”(association)	0.750
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
CCAR1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	CCAR1	psi-mi:“MI:0915”(physical association)	0.720
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
COMMD6	VPS26C	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
U2AF2	CCAR1	psi-mi:“MI:0915”(physical association)	0.640
RBM10	CCAR1	psi-mi:“MI:0915”(physical association)	0.570
CCAR1	DNAAF6	psi-mi:“MI:0915”(physical association)	0.560
DNAAF6	CCAR1	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	CCAR1	psi-mi:“MI:0915”(physical association)	0.560
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	YWHAE	psi-mi:“MI:0914”(association)	0.530
ZYX	TBC1D10B	psi-mi:“MI:0914”(association)	0.530
SRSF5	CBX6	psi-mi:“MI:0914”(association)	0.530
TRIM63	CCAR1	psi-mi:“MI:0915”(physical association)	0.510
CCAR1	TRIM63	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (252): CCAR1 (Two-hybrid), PIH1D3 (Two-hybrid), CCAR1 (Affinity Capture-MS), CCAR1 (Affinity Capture-MS), CCAR1 (Affinity Capture-MS), CCAR1 (Affinity Capture-MS), ACTR1A (Co-fractionation), ACTR1B (Co-fractionation), CAND1 (Co-fractionation), CCAR1 (Co-fractionation), CCAR1 (Co-fractionation), DCTN1 (Co-fractionation), DCTN2 (Co-fractionation), DYNC1I2 (Co-fractionation), PCNA (Co-fractionation)

ESM2 similar proteins: A2RTL5, B2RY56, B3MJ69, B3N3F7, B4H732, B4II37, B4J497, B4KLY7, B4LIK8, B4MR46, B4NYV0, B4QCR6, F4IDY7, O15042, P0C1J2, P34433, P40818, P49756, P97496, Q10580, Q17FR9, Q28WQ8, Q2T9I5, Q4KME6, Q5PQR4, Q5R7X2, Q5TUF1, Q5ZKG2, Q641G3, Q68FU8, Q6GLQ4, Q6NV83, Q6PDG5, Q6Y7W6, Q6Y7W8, Q7ZYR8, Q803E1, Q8CH02, Q8CH18, Q8IX12

Diamond homologs: F4IS91, Q8CH18, Q8IX12, Q5R8S0, Q641G3, Q8N163, Q8VDP4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA Polyadenylation	24	18.2×	2e-21
mRNA Splicing	17	16.1×	4e-14
Processing of Capped Intron-Containing Pre-mRNA	21	14.9×	8e-17
mRNA Splicing - Major Pathway	30	14.1×	9e-24
mRNA 3’-end processing	8	13.6×	8e-06
mRNA Splicing - Minor Pathway	6	11.6×	7e-04
RNA Polymerase II Transcription Termination	6	11.4×	7e-04
CHD1 and CHD2 subfamily	12	11.2×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
regulation of mRNA splicing, via spliceosome	5	31.9×	9e-05
negative regulation of mRNA splicing, via spliceosome	5	27.6×	2e-04
U2-type prespliceosome assembly	6	26.9×	2e-05
RNA splicing, via transesterification reactions	5	22.4×	4e-04
spliceosomal complex assembly	5	21.6×	4e-04
mRNA splicing, via spliceosome	20	13.2×	5e-14
positive regulation of transcription elongation by RNA polymerase II	6	13.0×	8e-04
RNA processing	7	11.0×	4e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — MBL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4295 predictions. Top by Δscore:

Variant	Effect	Δscore
10:68736862:T:TA	acceptor_gain	1.0000
10:68736869:A:AG	acceptor_gain	1.0000
10:68736870:T:G	acceptor_gain	1.0000
10:68736874:A:AG	acceptor_gain	1.0000
10:68736874:AGCT:A	acceptor_gain	1.0000
10:68736875:G:GT	acceptor_gain	1.0000
10:68736875:GC:G	acceptor_gain	1.0000
10:68736875:GCT:G	acceptor_gain	1.0000
10:68736875:GCTG:G	acceptor_gain	1.0000
10:68736875:GCTGC:G	acceptor_gain	1.0000
10:68737045:ACAG:A	donor_gain	1.0000
10:68737048:GGTAA:G	donor_loss	1.0000
10:68737049:G:GA	donor_loss	1.0000
10:68737049:G:GG	donor_gain	1.0000
10:68737050:T:A	donor_loss	1.0000
10:68740627:A:AG	acceptor_gain	1.0000
10:68740628:G:GA	acceptor_gain	1.0000
10:68747158:C:G	acceptor_gain	1.0000
10:68747159:A:AG	acceptor_gain	1.0000
10:68747159:AGT:A	acceptor_gain	1.0000
10:68747160:G:GG	acceptor_gain	1.0000
10:68747160:GT:G	acceptor_gain	1.0000
10:68747160:GTG:G	acceptor_gain	1.0000
10:68747160:GTGCT:G	acceptor_gain	1.0000
10:68747271:ATCAG:A	donor_loss	1.0000
10:68747272:TCAGG:T	donor_loss	1.0000
10:68747273:CAGG:C	donor_loss	1.0000
10:68747274:AG:A	donor_loss	1.0000
10:68747275:GGT:G	donor_loss	1.0000
10:68747276:G:A	donor_loss	1.0000

AlphaMissense

7578 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:68742493:C:A	R148S	1.000
10:68742499:T:C	F150L	1.000
10:68742500:T:C	F150S	1.000
10:68742500:T:G	F150C	1.000
10:68742501:C:A	F150L	1.000
10:68742501:C:G	F150L	1.000
10:68742505:G:A	G152R	1.000
10:68742505:G:C	G152R	1.000
10:68742505:G:T	G152W	1.000
10:68742506:G:A	G152E	1.000
10:68742512:T:A	V154D	1.000
10:68742532:T:C	F161L	1.000
10:68742534:T:A	F161L	1.000
10:68742534:T:G	F161L	1.000
10:68742535:G:A	G162R	1.000
10:68742535:G:C	G162R	1.000
10:68742536:G:A	G162E	1.000
10:68742542:T:A	V164E	1.000
10:68742554:T:A	V168E	1.000
10:68742560:T:C	F170S	1.000
10:68747199:T:A	V186E	1.000
10:68747205:T:A	V188D	1.000
10:68747210:G:C	A190P	1.000
10:68747211:C:A	A190D	1.000
10:68747234:T:C	F198L	1.000
10:68747235:T:C	F198S	1.000
10:68747236:T:A	F198L	1.000
10:68747236:T:G	F198L	1.000
10:68747240:T:A	W200R	1.000
10:68747240:T:C	W200R	1.000

dbSNP variants (sampled 300 via entrez): RS1000119523 (10:68719425 A>G), RS1000159818 (10:68734094 T>C), RS1000168421 (10:68747893 G>A), RS1000236303 (10:68740012 T>C), RS1000271635 (10:68751008 A>G), RS1000289002 (10:68791402 T>A,G), RS1000308769 (10:68790747 G>A), RS1000309482 (10:68773334 A>G), RS1000313966 (10:68769783 T>C), RS1000324355 (10:68751241 A>C,G), RS1000366841 (10:68728404 T>A), RS1000378887 (10:68745015 T>A), RS1000396074 (10:68784986 C>T), RS1000434815 (10:68724302 T>TA), RS1000448401 (10:68720725 G>A)

Disease associations

OMIM: gene MIM:612569 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003465_24	Cannabis dependence symptom count	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008457	cannabis dependence measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	6
1-(2-chlorobenzyl)-5’-phenyl-3’H-spiro(indoline-3,2’-(1,3,4)thiadiazol)-2-one	decreases reaction, affects reaction, increases activity, increases phosphorylation, affects binding (+2 more)	4
Doxorubicin	increases expression, increases phosphorylation, affects cotreatment, affects binding, increases reaction (+2 more)	4
Bortezomib	increases expression	2
Nocodazole	affects localization, decreases reaction, affects binding, increases reaction, increases expression	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
JNK-IN-8	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
kojic acid	increases expression	1
beta-lapachone	decreases expression	1
cypermethrin	increases expression	1
sodium arsenite	affects localization, decreases reaction	1
sulindac sulfide	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Arbutin	increases expression	1
Benztropine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cannabidiol	increases expression	1
Clozapine	increases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8IJ	Ubigene HCT 116 CCAR1 KO	Cancer cell line	Male
CVCL_D9B6	Ubigene HEK293 CCAR1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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