CHTOP

Summary

CHTOP (chromatin target of PRMT1, HGNC:24511) is a protein-coding gene on chromosome 1q21.3, encoding Chromatin target of PRMT1 protein (Q9Y3Y2). Plays an important role in the ligand-dependent activation of estrogen receptor target genes. It is a selective cancer dependency (DepMap: 21.4% of cell lines).

This gene encodes a small nuclear protein that is characterized by an arginine and glycine rich region. This protein may have an important role in the regulation of fetal globin gene expression and in the activation of estrogen-responsive genes. A recent study reported that this protein binds 5-hydroxymethylcytosine (5hmC) and associates with an arginine methyltransferase complex (methylosome), which promotes methylation of arginine 3 of histone H4 (H4R3) and activation of genes involved in glioblastomagenesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 26097 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total
• GTEx eGene: eQTL in 23 tissues, sQTL in 5 (q < 0.05)
• Cancer dependency (DepMap): dependent in 21.4% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.77 (unconstrained)
• MANE Select transcript: NM_015607
• Notable: 55 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24511
Approved symbol	CHTOP
Name	chromatin target of PRMT1
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP547E1010, SRAG, FOP
Ensembl gene	ENSG00000160679
Ensembl biotype	protein_coding
OMIM	614206
Entrez	26097

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000368694

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

ENST00000368694, ENST00000368686, ENST00000368687, ENST00000368690, ENST00000403433, ENST00000495554, ENST00000614256, ENST00000710369

RefSeq mRNA: 4 — MANE Select: NM_015607 NM_001206612, NM_001244664, NM_001317077, NM_015607

CCDS: CCDS1048, CCDS72917, CCDS72918, CCDS81380

Canonical transcript exons

ENST00000368694 — 6 exons

Exon	Start	End
ENSE00001072605	153636572	153636653
ENSE00001176707	153643227	153643364
ENSE00001176715	153638295	153638448
ENSE00001176723	153642246	153642429
ENSE00004011689	153634066	153634343
ENSE00004807053	153645064	153646306

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.7656 / max 453.2079, expressed in 1827 samples.

Highest expression (Bgee): tendon of biceps brachii, ventricular zone, ganglionic eminence, body of pancreas, embryo.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CHTOP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	9.5e-96	-0.52	1:153637410:C:G
Thyroid	eqtl	3.2e-21	+0.28	1:153634375:A:G
Heart Left Ventricle	sqtl	1.6e-19	-0.64	1:153637541:A:G
Heart Atrial Appendage	sqtl	3.9e-19	+0.69	1:153637410:C:G
Heart Atrial Appendage	eqtl	3.5e-15	-0.29	1:153637410:C:G
Artery Tibial	eqtl	3.4e-10	-0.19	1:153632043:G:A
Heart Left Ventricle	eqtl	8.8e-10	-0.22	1:153637541:A:G
Esophagus Mucosa	eqtl	1.1e-09	+0.20	1:153634375:A:G
Nerve Tibial	eqtl	7.4e-08	-0.14	1:153647747:T:C
Colon Transverse	eqtl	1.6e-07	+0.22	1:153632784:G:A
Spleen	eqtl	2.8e-05	+0.31	1:153632380:A:T
Muscle Skeletal	sqtl	5.5e-05	+0.26	1:153635640:G:C
Prostate	eqtl	1.0e-04	+0.24	1:153661582:G:T
Lung	eqtl	4.2e-04	+0.13	1:153683929:C:G
Esophagus Muscularis	eqtl	4.7e-04	-0.16	1:154008428:T:G
Adrenal Gland	eqtl	5.5e-04	-0.32	1:153582942:T:G
Colon Sigmoid	eqtl	1.9e-03	-0.17	1:153683876:T:G
Cells Cultured fibroblasts	eqtl	2.1e-03	-0.13	1:153634941:C:T
Adipose Visceral Omentum	sqtl	6.4e-03	+1.07	1:153181668:C:CATTGTCTT
Esophagus Gastroesophageal Junction	eqtl	6.8e-03	-0.19	1:153635640:G:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
5418	72.6606	1827
5417	2.2857	1389
5416	0.8193	469

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.53	gold quality
ventricular zone	UBERON:0003053	97.74	gold quality
ganglionic eminence	UBERON:0004023	97.47	gold quality
body of pancreas	UBERON:0001150	96.90	gold quality
embryo	UBERON:0000922	96.63	gold quality
right lobe of thyroid gland	UBERON:0001119	96.55	gold quality
granulocyte	CL:0000094	96.43	gold quality
cortical plate	UBERON:0005343	96.41	gold quality
left lobe of thyroid gland	UBERON:0001120	96.22	gold quality
endocervix	UBERON:0000458	96.10	gold quality
left ovary	UBERON:0002119	96.00	gold quality
thyroid gland	UBERON:0002046	95.84	gold quality
right ovary	UBERON:0002118	95.80	gold quality
metanephros cortex	UBERON:0010533	95.80	gold quality
gastrocnemius	UBERON:0001388	95.79	gold quality
body of uterus	UBERON:0009853	95.79	gold quality
ectocervix	UBERON:0012249	95.76	gold quality
medial globus pallidus	UBERON:0002477	95.74	gold quality
muscle of leg	UBERON:0001383	95.64	gold quality
apex of heart	UBERON:0002098	95.62	gold quality
cerebellar hemisphere	UBERON:0002245	95.62	gold quality
right uterine tube	UBERON:0001302	95.58	gold quality
cerebellar cortex	UBERON:0002129	95.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.47	gold quality
body of stomach	UBERON:0001161	95.40	gold quality
monocyte	CL:0000576	95.38	gold quality
spleen	UBERON:0002106	95.37	gold quality
leukocyte	CL:0000738	95.32	gold quality
mucosa of transverse colon	UBERON:0004991	95.32	gold quality
skin of abdomen	UBERON:0001416	95.31	gold quality
minor salivary gland	UBERON:0001830	95.31	gold quality
mononuclear cell	CL:0000842	95.30	gold quality
muscle organ	UBERON:0001630	95.27	gold quality
left uterine tube	UBERON:0001303	95.21	gold quality
heart left ventricle	UBERON:0002084	95.21	gold quality
ovary	UBERON:0000992	95.17	gold quality
lymph node	UBERON:0000029	95.15	gold quality
vagina	UBERON:0000996	95.13	gold quality
skin of leg	UBERON:0001511	95.12	gold quality
cerebellum	UBERON:0002037	95.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.12	gold quality
lower esophagus mucosa	UBERON:0035834	95.07	gold quality
cardiac ventricle	UBERON:0002082	95.05	gold quality
type B pancreatic cell	CL:0000169	95.03	silver quality
pancreas	UBERON:0001264	95.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.00	gold quality
adenohypophysis	UBERON:0002196	94.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.96	gold quality
transverse colon	UBERON:0001157	94.92	gold quality
right atrium auricular region	UBERON:0006631	94.90	gold quality
gluteal muscle	UBERON:0002000	94.89	gold quality
biceps brachii	UBERON:0001507	94.83	gold quality
pituitary gland	UBERON:0000007	94.82	gold quality
triceps brachii	UBERON:0001509	94.76	gold quality
esophagus mucosa	UBERON:0002469	94.68	gold quality
right adrenal gland	UBERON:0001233	94.66	gold quality
skeletal muscle tissue	UBERON:0001134	94.64	gold quality
heart	UBERON:0000948	94.62	gold quality
globus pallidus	UBERON:0001875	94.57	gold quality
mucosa of stomach	UBERON:0001199	94.52	gold quality
tibial nerve	UBERON:0001323	94.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.50	gold quality
mouth mucosa	UBERON:0003729	94.47	gold quality
right adrenal gland cortex	UBERON:0035827	94.46	gold quality
spinal cord	UBERON:0002240	94.45	gold quality
cardiac atrium	UBERON:0002081	94.43	gold quality
saliva-secreting gland	UBERON:0001044	94.40	gold quality
peritoneum	UBERON:0002358	94.38	gold quality
omental fat pad	UBERON:0010414	94.38	gold quality
stomach	UBERON:0000945	94.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.35	gold quality
olfactory bulb	UBERON:0002264	94.33	silver quality
esophagus	UBERON:0001043	94.30	gold quality
left adrenal gland	UBERON:0001234	94.30	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.28	gold quality
right lung	UBERON:0002167	94.26	gold quality
zone of skin	UBERON:0000014	94.23	gold quality
muscle tissue	UBERON:0002385	94.21	gold quality
left adrenal gland cortex	UBERON:0035825	94.21	gold quality
descending thoracic aorta	UBERON:0002345	94.19	gold quality
vastus lateralis	UBERON:0001379	94.17	gold quality
small intestine	UBERON:0002108	94.15	gold quality
diaphragm	UBERON:0001103	94.12	gold quality
lower esophagus	UBERON:0013473	94.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.12	gold quality
female reproductive system	UBERON:0000474	94.11	gold quality
endometrium	UBERON:0001295	94.04	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.04	gold quality
left coronary artery	UBERON:0001626	94.01	gold quality
rectum	UBERON:0001052	94.00	gold quality
sigmoid colon	UBERON:0001159	93.98	gold quality
vermiform appendix	UBERON:0001154	93.97	gold quality
upper lobe of left lung	UBERON:0008952	93.97	gold quality
fundus of stomach	UBERON:0001160	93.96	gold quality
quadriceps femoris	UBERON:0001377	93.94	gold quality
deltoid	UBERON:0001476	93.94	gold quality
smooth muscle tissue	UBERON:0001135	93.92	gold quality
nucleus accumbens	UBERON:0001882	93.92	gold quality
colon	UBERON:0001155	93.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	no	2.28
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	134.2
Corpus callosum	tissue	118.2
Skeletal muscle	tissue	116.6	high
Frontal cortex	tissue	114.9
Spinal cord	tissue	102.5
Midbrain	tissue	94.8
Medulla oblongata	tissue	93.8
Superior colliculi	tissue	92.3
Pons	tissue	89.7
Substantia nigra	tissue	89.4
Putamen	tissue	88.2
Thalamus	tissue	84.8
Periaqueductal gray	tissue	84.7
Hypothalamus	tissue	83.3
Cerebellum	tissue	81.6	high
Septum	tissue	81.6
Ventral forebrain	tissue	78.3
Hippocampal formation	tissue	77.2
Olfactory bulb	tissue	75.6
Basal ganglia	tissue	74.4	high
Cerebral cortex	tissue	72.5	high
Motor cortex	tissue	72.5
Somatosensory cortex	tissue	70.6
Retrosplenial cortex	tissue	69.4
Retrosplenial and cingulate cortex	tissue	69.3
Entorhinal cortex	tissue	68.3
Amygdala	tissue	68.1
Prefrontal cortex	tissue	67.6
Temporal cortex	tissue	67.5
Occipital cortex	tissue	66.0
Insular cortex	tissue	64.5
Tongue	tissue	63.8
Thymus	tissue	61.2
Bone marrow	tissue	59.1	high
Retina	tissue	55.5
Vagina	tissue	46.4	high
Pituitary gland	tissue	46.3
Heart muscle	tissue	43.8	high
Lymph node	tissue	43.6	medium
Nucleus accumbens	tissue	42.4
Tonsil	tissue	41.6	high
Ovary	tissue	40.7	high
Choroid plexus	tissue	40.1
Skin 1	tissue	38.7	high
Spleen	tissue	37.2	medium
Pancreas	tissue	36.2	high
Locus coeruleus	tissue	35.6
Breast	tissue	35.3	high
Endometrium 1	tissue	35.2	medium
Postcentral gyrus	tissue	34.9
Fallopian tube	tissue	34.9	high
Appendix	tissue	34.5	high
Hippocampus	tissue	34.3	high
Epididymis	tissue	34.1	high
Parathyroid gland	tissue	33.8	high
Thyroid gland	tissue	32.2	high
Stomach 1	tissue	31.8	high
Placenta	tissue	31.4	high
Adrenal gland	tissue	30.9	high
Rectum	tissue	30.7	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (118.2), Ventral spinal cord (102.5), Dorsal spinal cord (100.6), Dorsal hippocampus (77.2), Ventral hippocampus (71.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 79 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Functional genomics

gnomAD constraint: pLI 0.00431, LOEUF 0.768, missense Z 1.71 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000368694 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:153,636,589–153,642,288	73 / 108.9	0.67	no
1:153,642,289–153,645,150	168 / 179.9	0.93	no
1:153,645,151–153,645,266	22 / 47.9	0.46	no
DepMap (CRISPR cell-line fitness): dependent in 21.4% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): Mac-2A (-1.327), C-33 A (-1.178), OCI-LY-19 (-1.159), UM-UC7 (-1.08), LO68 (-1.036), HUP-T3 (-1.032), EOL-1 (-1.001), A2058 (-0.99), RI-1 (-0.972), 170-MG-BA (-0.95), COLO-680N (-0.94), CAL-62 (-0.926), NMB (-0.926), NP 2 (-0.919), NCI-H1568 (-0.918).

Literature-anchored findings (GeneRIF, showing 10)

• The reduction in SRAG protein that occurs in proliferating cells was mapped with inhibitors to the G(2)/M phase of the cell cycle. As expected, the overexpression of SRAG reduced the percentage of cells in the G(2)/M phase and increased cell death. (PMID:19254951)
• Fop is tightly associated with chromatin, and that it is modified by both asymmetric and symmetric arginine methylation in vivo. Fop plays an important role in the ligand-dependent activation of estrogen receptor target genes, including TFF1 (pS2). (PMID:19858291)
• The recently identified chromatin factor Friend of Prmt1 (FOP) is a critical modulator of gamma-globin gene expression. (PMID:20688955)
• Chtop is a component of the dynamic TREX mRNA export complex that, along with Alyref, activates the ATPase and RNA helicase activities of Uap56. (PMID:23299939)
• a spatial map is produced in living cells of the sites for the interaction of two TREX subunits, Alyref and Chtop, with Nxf1. (PMID:23826332)
• Results suggest that 5hmC plays a critical role in glioblastomagenesis by recruiting the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of cancer-related genes. (PMID:25284789)
• the cellular level of Chtop is autoregulated via Int2 retention of its own mRNA, which subsequently undergoes NMD. (PMID:27683223)
• These findings first suggest that CHTOP, as a highly expressed protein in ovarian cancer, is closely associated with the malignant phenotypes of epithelial ovarian cancer cells, including metastasis, chemoresistance, and stemness, which highlights a promising role of CHTOP in ovarian cancer targeted therapy. (PMID:30910850)
• Circulating unmethylated CHTOP and INS DNA fragments provide evidence of possible islet cell death in youth with obesity and diabetes. (PMID:32736653)
• Type I and II PRMTs inversely regulate post-transcriptional intron detention through Sm and CHTOP methylation. (PMID:34984976)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	chtopa	ENSDARG00000057234
danio_rerio	chtopb	ENSDARG00000070430
mus_musculus	Chtop	ENSMUSG00000001017
rattus_norvegicus	Chtop	ENSRNOG00000012760
rattus_norvegicus	Chtopl1	ENSRNOG00000058457
caenorhabditis_elegans		WBGENE00000121
caenorhabditis_elegans		WBGENE00000122

Paralogs (2): POLDIP3 (ENSG00000100227), ALYREF (ENSG00000183684)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913761) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 100 distinct phenotype terms.

Mouse phenotype (MP)	Records
double outlet right ventricle	2
bicuspid aortic valve	2
absent vertebrae	1
abnormal vertebral body morphology	1
rib bifurcation	1
rib fusion	1
scoliosis	1
abnormal maxilla morphology	1
abnormal rectum morphology	1
abnormal small intestine placement	1
abnormal salivary gland morphology	1
abnormal pineal gland morphology	1
abnormal thyroid gland morphology	1
absent spleen	1
spleen hypoplasia	1
abnormal forebrain morphology	1
abnormal choroid plexus morphology	1
fused dorsal root ganglion	1
small superior cervical ganglion	1
small nodose ganglion	1
internal hemorrhage	1
abnormal placenta morphology	1
abnormal eye morphology	1
persistent truncus arteriosus	1
abnormal atrioventricular valve morphology	1

+75 more (showing top 25).

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	Q3SYW9	99.6%	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
MIR8083	ncRNA	102466879
SNAPIN	protein-coding	23557
ILF2	protein-coding	3608
NPR1	protein-coding	4881
S100A13	protein-coding	6284
S100A16	protein-coding	140576
S100A14	protein-coding	57402
S100A1	protein-coding	6271
S100A2	protein-coding	6273
TRX-CAT1-1	tRNA	100189015

Protein

Protein identifiers

Chromatin target of PRMT1 protein — Q9Y3Y2 (reviewed: Q9Y3Y2)

Alternative names: Friend of PRMT1 protein, Small arginine- and glycine-rich protein

All UniProt accessions (5): A0A087X1B7, A0AA34QVV3, Q9Y3Y2, Q5T7Y7, X6R700

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the ligand-dependent activation of estrogen receptor target genes. May play a role in the silencing of fetal globin genes. Recruits the 5FMC complex to ZNF148, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Plays an important role in the tumorigenicity of glioblastoma cells. Binds to 5-hydroxymethylcytosine (5hmC) and associates with the methylosome complex containing PRMT1, PRMT5, MEP50 and ERH. The CHTOP-methylosome complex associated with 5hmC is recruited to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastomagenesis. Required for effective mRNA nuclear export and is a component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5’ end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. The TREX complex is essential for the export of Kaposi’s sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. Stimulates DDX39B ATPase and helicase activities. In cooperation with ALYREF/THOC4 enhances NXF1 RNA binding activity.

Subunit / interactions. Interacts with PRMT1 and PRMT5. Interacts with the 5FMC complex; the interaction is methylation-dependent. Interacts with FYTTD1, SET and PRC1 complex members CBX4, RNF2 and PHC2; the interactions are methylation-independent. Interacts with ZNF148. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; TREX seems to have dynamic structure involving ATP-dependent remodeling; in the complex interacts (methylated) with ALYREF/THOC4 and with DDX39B in a methylation-independent manner. Interacts (methylated) with NXF1; the interaction is mutually exclusive with the NXF1:THOC5 interaction. Interacts with WDR77 and ERH.

Subcellular location. Nucleus. Nucleolus. Nucleoplasm. Nucleus speckle.

Tissue specificity. Expressed in an erythroid progenitor cell line derived from peripheral blood. Expressed in glioblastoma cells.

Post-translational modifications. Asymmetrically methylated by PRMT1. Symmetrically methylated by PRMT5.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y3Y2-1	1	yes
Q9Y3Y2-3	2
Q9Y3Y2-4	3, SRAG-5

RefSeq proteins (4): NP_001193541, NP_001231593, NP_001304006, NP_056422* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025715	YRA2_C	Domain
IPR052656	CTOP_PRMT1	Family

Pfam: PF13865

UniProt features (23 total): modified residue 6, mutagenesis site 5, sequence conflict 3, splice variant 2, region of interest 2, initiator methionine 1, chain 1, cross-link 1, short sequence motif 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3Y2-F1	62.64	0.09

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles

Antibody reliability (HPA): IH approved · IF supported

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 (7)

Type	Positions
Phosphoserine	64, 40, 49
Phosphothreonine	242, 33
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	70
N-acetylalanine	2

Mutagenesis-validated functional residues (5)

Position	Phenotype
195	loss of 5hmc binding; when associated with a-197; a-199; a-201 and a-203.
197	loss of 5hmc binding; when associated with a-195; a-199; a-201 and a-203.
199	loss of 5hmc binding; when associated with a-195; a-197; a-201 and a-203.
201	loss of 5hmc binding; when associated with a-195; a-197; a-199 and a-203.
203	loss of 5hmc binding; when associated with a-195; a-197; a-199 and a-201.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript	curated
R-HSA-72187	mRNA 3’-end processing	curated
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-73856	RNA Polymerase II Transcription Termination	—
R-HSA-72202	Transport of Mature Transcript to Cytoplasm	—

MSigDB gene sets: 175 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, WANG_CLIM2_TARGETS_UP, GCM_GSPT1, GCM_ZNF198, MODULE_493, YY1_Q6, GGCNKCCATNK_UNKNOWN, GCM_BCL2L1, GOBP_NUCLEAR_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, YY1_02

GO Biological Process (6): chromatin remodeling (GO:0006338), DNA-templated transcription (GO:0006351), mRNA export from nucleus (GO:0006406), positive regulation of ATP-dependent activity (GO:0032781), positive regulation of helicase activity (GO:0051096), mRNA transport (GO:0051028)

GO Molecular Function (3): RNA binding (GO:0003723), methyl-CpG binding (GO:0008327), protein binding (GO:0005515)

GO Cellular Component (5): transcription export complex (GO:0000346), nucleoplasm (GO:0005654), nucleolus (GO:0005730), nuclear speck (GO:0016607), nucleus (GO:0005634)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Processing of Capped Intron-Containing Pre-mRNA	2
Transport of Mature Transcript to Cytoplasm	1
RNA Polymerase II Transcription	1
Metabolism of RNA	1
Gene expression (Transcription)	1

GO top-level categories

22 GO namespaces:

Category	Terms
gene expression	2
nuclear lumen	2
chromatin organization	1
RNA biosynthetic process	1
RNA export from nucleus	1
mRNA transport	1
regulation of ATP-dependent activity	1
positive regulation of molecular function	1
ATP-dependent activity	1
helicase activity	1
positive regulation of ATP-dependent activity	1
positive regulation of catalytic activity	1
RNA transport	1
nucleic acid binding	1
nucleotide binding	1
sequence-specific DNA binding	1
binding	1
nuclear protein-containing complex	1
cellular anatomical structure	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
chromatin remodeling	BP	mutant phenotype
mRNA export from nucleus	BP	direct assay
positive regulation of ATP-dependent activity	BP	direct assay
positive regulation of helicase activity	BP	direct assay
nuclear speck	CC	direct assay
transcription export complex	CC	direct assay
RNA binding	MF	high-throughput assay
methyl-CpG binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,544 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHTOP	THOC5	Q13769	705
CHTOP	FYTTD1	Q96QD9	663
CHTOP	SARNP	P82979	660
CHTOP	THOC2	Q8NI27	635
CHTOP	THOC1	Q96FV9	629
CHTOP	DDX39B	Q13838	626
CHTOP	THOC7	Q6I9Y2	615
CHTOP	ALYREF	Q86V81	610
CHTOP	ZC3H11A	O75152	601
CHTOP	POLDIP3	Q9BY77	599
CHTOP	THOC6	Q86W42	582
CHTOP	NXF1	Q9UBU9	573
CHTOP	THOC3	Q96J01	552
CHTOP	PRMT1	Q99873	542
CHTOP	LUZP4	Q9P127	500

IntAct

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

22 partners by confidence:

Partner	Interaction type	MIscore	Records
DDX39B	physical association	0.870	5
ERH	physical association	0.850	4
ALYREF	physical association	0.680	2
PRMT1	physical association	0.670	2
THOC5	association	0.660	3
NXF1	physical association	0.650	7
SRPK2	phosphorylation reaction	0.590	1
KHDRBS2	physical association	0.560	3
SMN1	physical association	0.560	3
CENPC	physical association	0.400	1
DDX39A	physical association	0.400	1
MAP4	physical association	0.400	1
MTIF2	physical association	0.400	1
SAP18	physical association	0.400	1
ZNF585A	physical association	0.400	1
GSK3A	physical association	0.370	1
C1orf226	association	0.350	1
MYH7B	association	0.350	1
PRMT5	association	0.350	1
ZC3H14	association	0.350	1
SRSF2	colocalization	0.270	1
ATG12	physical association	0.000	1

BioGRID (338 interactions; top human partners by supporting records): ERH (Two-hybrid; 11 records), DDX39B (Affinity Capture-MS; 10 records), FYTTD1 (Affinity Capture-MS; 7 records), PRMT1 (Biochemical Activity; 7 records), DDX39A (Two-hybrid; 4 records), PRMT5 (Affinity Capture-MS; 3 records), PRMT8 (Affinity Capture-MS; 3 records), RSPO1 (Affinity Capture-MS; 3 records), SRPK2 (Affinity Capture-MS; 3 records), WDR77 (Affinity Capture-MS; 3 records), ALYREF (Cross-Linking-MS (XL-MS); 2 records), APP (Affinity Capture-MS; 2 records), BRD4 (Affinity Capture-MS; 2 records), C17orf85 (Proximity Label-MS; 2 records), CENPC (Cross-Linking-MS (XL-MS); 2 records)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
CHTOP-ERH-PRMT1-PRMT5-WDR77 complex	5	PRMT5, WDR77, CHTOP, ERH, PRMT1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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 3’-end processing	5	57.9×	8e-07
Transport of Mature mRNA derived from an Intron-Containing Transcript	6	53.7×	7e-08
Metabolism of RNA	5	12.3×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	5	70.4×	5e-07
RNA splicing	7	29.4×	3e-07
mRNA processing	5	18.8×	2e-04

Disease & clinical

Genetic variants

Variant evidence for CHTOP: 55 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	3
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 439):

Position(s)	Effect	Δscore	Sites
1:153636570–153636571	acceptor_loss	1.0000	5
1:153634344–153634345	donor_loss	0.9900	4
1:153636571	acceptor_loss	0.9900
1:153636686	donor_gain	0.9900
1:153636743	donor_gain	0.9900
1:153638684	donor_gain	0.9900
1:153634344	donor_loss	0.9700
1:153638273	acceptor_gain	0.9700
1:153645056	acceptor_gain	0.9600
1:153636654–153636655	donor_loss	0.9500	6

AlphaMissense

887 missense substitutions predicted likely pathogenic (of 1,541 scored), across 218 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
M224	9	0.996	1.000
M239	9	0.994	1.000
M59	9	0.991	1.000
D217	8	1.000	1.000
D232	8	1.000	1.000
D221	8	0.998	1.000
F23	8	0.997	1.000
D236	8	0.995	0.999
N52	8	0.993	0.999
N20	8	0.928	0.999
S13	8	0.921	0.998
H230	8	0.847	0.986
E60	7	0.974	0.997
S49	7	0.968	0.999
E234	7	0.962	0.997
E214	7	0.949	0.995
Q58	7	0.943	0.999
I84	7	0.938	0.999
E21	7	0.935	0.998
M26	7	0.929	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.1e-06
Skin Cutaneous Melanoma (TCGA)	unfavorable	0.000281
Prostate Adenocarcinoma (TCGA)	unfavorable	0.000905

Disease associations

OMIM: gene MIM:614206 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
sodium arsenite	affects binding, increases reaction, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases expression, increases methylation	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance, affects expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	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
abrine	increases expression	1
bisphenol S	affects expression	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.