CTDP1

Summary

CTDP1 (CTD phosphatase subunit 1, HGNC:2498) is a protein-coding gene on chromosome 18q23, encoding RNA polymerase II subunit A C-terminal domain phosphatase (Q9Y5B0). Processively dephosphorylates ‘Ser-2’ and ‘Ser-5’ of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

This gene encodes a protein which interacts with the carboxy-terminus of the RAP74 subunit of transcription initiation factor TFIIF, and functions as a phosphatase that processively dephosphorylates the C-terminus of POLR2A (a subunit of RNA polymerase II), making it available for initiation of gene expression. Mutations in this gene are associated with congenital cataracts, facial dysmorphism and neuropathy syndrome (CCFDN). Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 9150 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital cataracts-facial dysmorphism-neuropathy syndrome (Definitive, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 721 total — 1 pathogenic
• Phenotypes (HPO): 56
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_004715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2498
Approved symbol	CTDP1
Name	CTD phosphatase subunit 1
Location	18q23
Locus type	gene with protein product
Status	Approved
Aliases	FCP1
Ensembl gene	ENSG00000060069
Ensembl biotype	protein_coding
OMIM	604927
Entrez	9150

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000075430, ENST00000299543, ENST00000585951, ENST00000587623, ENST00000590599, ENST00000590635, ENST00000591598, ENST00000613122, ENST00000857536, ENST00000857537, ENST00000857538, ENST00000857539, ENST00000938121

RefSeq mRNA: 4 — MANE Select: NM_004715 NM_001202504, NM_001318511, NM_004715, NM_048368

CCDS: CCDS12017, CCDS12018

Canonical transcript exons

ENST00000613122 — 13 exons

Exon	Start	End
ENSE00000670824	79728907	79729069
ENSE00000898301	79717535	79717676
ENSE00000898302	79717810	79718016
ENSE00001102875	79697860	79697988
ENSE00001102905	79714491	79715528
ENSE00001102920	79704767	79704917
ENSE00001167951	79712972	79713138
ENSE00001167961	79710346	79710436
ENSE00001167982	79695977	79696070
ENSE00001429543	79679803	79680261
ENSE00003470236	79736355	79736521
ENSE00003691370	79695225	79695308
ENSE00003717925	79753652	79754503

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 89.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.0164 / max 670.5165, expressed in 1811 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170910	18.2109	1809
170911	0.8055	234

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	89.47	gold quality
right testis	UBERON:0004534	89.44	gold quality
skin of leg	UBERON:0001511	87.98	gold quality
oocyte	CL:0000023	87.83	gold quality
granulocyte	CL:0000094	87.57	gold quality
triceps brachii	UBERON:0001509	87.06	gold quality
testis	UBERON:0000473	86.77	gold quality
blood	UBERON:0000178	86.69	gold quality
mucosa of transverse colon	UBERON:0004991	86.61	gold quality
skin of abdomen	UBERON:0001416	86.52	gold quality
secondary oocyte	CL:0000655	85.86	gold quality
monocyte	CL:0000576	85.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.52	gold quality
lower esophagus mucosa	UBERON:0035834	85.30	gold quality
leukocyte	CL:0000738	84.93	gold quality
sural nerve	UBERON:0015488	84.93	gold quality
mononuclear cell	CL:0000842	84.86	gold quality
apex of heart	UBERON:0002098	84.51	gold quality
zone of skin	UBERON:0000014	84.42	gold quality
spleen	UBERON:0002106	83.85	gold quality
transverse colon	UBERON:0001157	83.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.92	gold quality
lower esophagus	UBERON:0013473	82.91	gold quality
right lobe of liver	UBERON:0001114	82.88	gold quality
body of stomach	UBERON:0001161	82.59	gold quality
popliteal artery	UBERON:0002250	82.50	gold quality
gluteal muscle	UBERON:0002000	82.49	gold quality
tibial artery	UBERON:0007610	82.49	gold quality
gastrocnemius	UBERON:0001388	82.46	gold quality
right lung	UBERON:0002167	82.23	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting CTDP1, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-6769A-5P	97.99	64.16	851
HSA-MIR-411-5P	97.11	66.82	601
HSA-MIR-4491	96.53	66.20	935
HSA-MIR-4657	96.53	66.57	895

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 16)

• FCP1 augments tat transactivation of the HIV-1 long-terminal repeat (PMID:12036313)
• FCP1 is important for transcription elongation along with TFIIF (PMID:12370301)
• FCP1 binds to a groove of RAP74 between alpha-helices H2 and H3, without affecting the secondary structure of RAP74 C-terminal domain; FCP1 binds also to a groove of TFIIB core domain beween alpha helices D1 and E1 in the first cyclin repeat. (PMID:12578358)
• FCP1 kinase from HeLa cells is phosphorylated and affects transcription elongation (PMID:12591939)
• cocrystal structure of the winged-helix domain of human RNA polymerase II-associating protein 74 bound to the alpha-helical C terminus of human FCP1 (PMID:12591941)
• high-resolution solution structure of a cterRAP74cterFCP complex by NMR spectroscopy (PMID:12732728)
• Congenital cataracts facial dysmorphism neuropathy is caused by a single-nucleotide substitution in an antisense Alu element in intron 6 of CTDP1, resulting in a rare mechanism of aberrant splicing and an Alu insertion in the processed mRNA (PMID:14517542)
• found that FCP1 is a genuine substrate of PRMT5-methylation both in vivo and in vitro, and FCP1-associated PRMT5 can methylate histones H4 in vitro (PMID:15670829)
• Enhanced binding to RAP74 following phosphorylation. (PMID:15723517)
• These data suggest that icariin exerts its potent osteogenic effect through induction of Runx2 expression, production of BMP-4 and activation of BMP signaling. (PMID:18294453)
• NMR and thermodynamic studies further elucidate the complex molecular mechanism by which TFIIF and FCP1 cooperate for RNAPII recycling. (PMID:19215094)
• NMR assignments for C terminal region (PMID:19888685)
• although FCP1 is intrinsically disordered, the above 16 residues composing the RAP74 binding surface form nascent alpha-helical structure in the unbound state. (PMID:21672523)
• Data propose that Fcp1 has a crucial role in the liaison between dephosphorylation and ubiquitination that drives mitosis exit. (PMID:22692537)
• results demonstrated that CTDP1 was upregulated in human lung cancer tissues. In addition, it implied that CTDP1 played an important role in cell proliferation and may be a useful therapeutic target in human lung cancer. (PMID:26590573)
• Study identifies CTDP1 as an autoantigen specific for Behcet Disease. (PMID:27777341)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctdp1	ENSDARG00000017522
mus_musculus	Ctdp1	ENSMUSG00000033323
rattus_norvegicus	Ctdp1	ENSRNOG00000061474
drosophila_melanogaster	Fcp1	FBGN0035026
caenorhabditis_elegans	fcp-1	WBGENE00009479

Protein

Protein identifiers

RNA polymerase II subunit A C-terminal domain phosphatase — Q9Y5B0 (reviewed: Q9Y5B0)

Alternative names: TFIIF-associating CTD phosphatase

All UniProt accessions (4): Q9Y5B0, A0A0A0MR03, K7EJD2, K7EPW4

UniProt curated annotations — full annotation on UniProt →

Function. Processively dephosphorylates ‘Ser-2’ and ‘Ser-5’ of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit. This promotes the activity of RNA polymerase II. Plays a role in the exit from mitosis by dephosphorylating crucial mitotic substrates (USP44, CDC20 and WEE1) that are required for M-phase-promoting factor (MPF)/CDK1 inactivation.

Subunit / interactions. Homodimer. Interacts with GTF2F1. Interacts with WDR77, SNRPB and SNRNP70.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole. Midbody.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated. In the presence of TFIIF, the phosphorylated form has an increased CTD phosphatase activity. The phosphorylation is required for the physical interaction with GTF2F1.

Disease relevance. Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) [MIM:604168] An autosomal recessive developmental disorder characterized by a complex clinical phenotype with seemingly unrelated features involving multiple organs and systems. Developmental abnormalities include congenital cataracts and microcorneae, hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, facial dysmorphism and hypogonadism. Central nervous system involvement, with cerebral and spinal cord atrophy, may be the result of disrupted development with superimposed degenerative changes. Affected individuals are prone to severe rhabdomyolysis after viral infections and to serious complications related to general anesthesia (such as pulmonary edema and epileptic seizures). The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5B0-1	1	yes
Q9Y5B0-4	4

RefSeq proteins (4): NP_001189433, NP_001305440, NP_004706, NP_430255 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR004274	FCP1_dom	Domain
IPR011947	FCP1_euk	Domain
IPR015388	FCP1_C	Domain
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR039189	Fcp1	Family
IPR058785	BSH_FCP1	Domain

Pfam: PF00533, PF03031, PF09309, PF26077

Catalyzed reactions (Rhea), 2 shown:

• O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate (RHEA:20629)
• O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate (RHEA:47004)

UniProt features (41 total): sequence conflict 11, compositionally biased region 8, modified residue 8, sequence variant 4, region of interest 3, domain 2, helix 2, chain 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1J2X	X-RAY DIFFRACTION	2
1ONV	SOLUTION NMR
2K7L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5B0-F1	64.97	0.34

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 (8): 1, 395, 674, 740, 780, 839, 869, 872

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167242	Abortive elongation of HIV-1 transcript in the absence of Tat
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-75955	RNA Polymerase II Transcription Elongation

MSigDB gene sets: 331 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_GROWTH, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_GROWTH

GO Biological Process (7): transcription elongation by RNA polymerase II (GO:0006368), protein dephosphorylation (GO:0006470), exit from mitosis (GO:0010458), host-mediated activation of viral transcription (GO:0043923), cell division (GO:0051301), negative regulation of cell growth involved in cardiac muscle cell development (GO:0061052), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (7): TFIIF-class transcription factor complex binding (GO:0001096), phosphoprotein phosphatase activity (GO:0004721), RNA polymerase II CTD heptapeptide repeat phosphatase activity (GO:0008420), Tat protein binding (GO:0030957), protein serine/threonine phosphatase activity (GO:0004722), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (10): spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), spindle (GO:0005819), midbody (GO:0030496), protein-containing complex (GO:0032991), spindle midzone (GO:0051233), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Transcription of the HIV genome	5
HIV Transcription Elongation	3
RNA Polymerase II Transcription Elongation	2
RNA Polymerase II Transcription	2
Tat-mediated elongation of the HIV-1 transcript	1
Transcriptional Regulation by TP53	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
transcription by RNA polymerase II	2
spindle	2
intracellular membraneless organelle	2
DNA-templated transcription elongation	1
dephosphorylation	1
protein modification process	1
mitotic cell cycle phase transition	1
mitotic nuclear division	1
host-mediated perturbation of viral transcription	1
host-mediated activation of viral process	1
cellular process	1
negative regulation of cardiac muscle hypertrophy	1
negative regulation of cell growth	1
negative regulation of striated muscle cell differentiation	1
negative regulation of cardiac muscle tissue growth	1
cell growth involved in cardiac muscle cell development	1
regulation of cell growth involved in cardiac muscle cell development	1
regulation of DNA-templated transcription	1
RNA polymerase II general transcription initiation factor binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
protein serine/threonine phosphatase activity	1
RNA polymerase II CTD heptapeptide repeat modifying activity	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
phosphoprotein phosphatase activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
microtubule cytoskeleton	1
cellular_component	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1813 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTDP1	GTF2F1	P35269	996
CTDP1	GTF2F2	P13984	883
CTDP1	UBLCP1	Q8WVY7	873
CTDP1	CTDSP1	Q9GZU7	868
CTDP1	RPAP2	Q8IXW5	866
CTDP1	GTF2B	Q00403	849
CTDP1	POLR2A	P24928	843
CTDP1	SSU72	Q9NP77	821
CTDP1	CTDSPL	O15194	750
CTDP1	WDR77	Q9BQA1	747
CTDP1	CTDSP2	O14595	744
CTDP1	JAG2	Q9Y219	728
CTDP1	CCNK	O75909	720
CTDP1	PRMT5	O14744	712
CTDP1	SUPT5H	O00267	692

IntAct

59 interactions, top by confidence:

A	B	Type	Score
MED11	MED19	psi-mi:“MI:0914”(association)	0.840
POLR2G	POLR2D	psi-mi:“MI:0914”(association)	0.840
MED14	MED19	psi-mi:“MI:0914”(association)	0.790
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
POLR2A	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2C	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2D	POLR2C	psi-mi:“MI:0914”(association)	0.730
RPRD1B	RECQL5	psi-mi:“MI:0914”(association)	0.730
POLR2G	RECQL5	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR2B	CTDP1	psi-mi:“MI:0915”(physical association)	0.640
CTDP1	PRMT5	psi-mi:“MI:0915”(physical association)	0.590
CTDP1	FANCI	psi-mi:“MI:0915”(physical association)	0.580
GTF2F1	CTDP1	psi-mi:“MI:0407”(direct interaction)	0.560
CTDP1	GTF2F1	psi-mi:“MI:0407”(direct interaction)	0.560
CTDP1	POLR2A	psi-mi:“MI:0915”(physical association)	0.560
IWS1	SUPT5H	psi-mi:“MI:0914”(association)	0.530
NUF2	SPC24	psi-mi:“MI:0914”(association)	0.530
POLR2I	SUPT5H	psi-mi:“MI:0914”(association)	0.530
POLR2J	SUPT5H	psi-mi:“MI:0914”(association)	0.530
POLR2M	BIN1	psi-mi:“MI:0914”(association)	0.530
POLR2J	MED14	psi-mi:“MI:0914”(association)	0.530
STK38	CTDP1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (250): CTDP1 (Affinity Capture-MS), CTDP1 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), HMGB1 (Affinity Capture-MS), CSNK2B (Affinity Capture-MS), GTF2F1 (Affinity Capture-Western), POLR2A (Biochemical Activity), CTDP1 (Co-crystal Structure), POLR2A (Reconstituted Complex), CTDP1 (Affinity Capture-MS), CTDP1 (Affinity Capture-MS), CTDP1 (Affinity Capture-MS), CTDP1 (Affinity Capture-MS), CTDP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQ45, A0A1B0GWB2, A2A9T0, A6QPA0, A7MCY6, D3ZFB6, E9PUL5, E9Q0B3, F5GYI3, F5H4A9, J3QNX5, O70142, P0C1G7, P81408, P97764, P98077, Q148V8, Q15654, Q2KI80, Q3SX26, Q3SZL6, Q4V9L6, Q5FVJ4, Q5FW56, Q5RAC1, Q5T7N3, Q6DG50, Q6PAJ3, Q6PJ61, Q6ZMQ8, Q6ZNR0, Q6ZRV2, Q75VX8, Q7Z6L0, Q86UK7, Q86VE0, Q8BGW2, Q8BRJ3, Q8BX43, Q8C0R7

Diamond homologs: A4QNX6, M9PFN0, O13636, O14595, O15194, O59718, O95476, P0CN66, P0CN67, P38757, P58465, P58466, Q02776, Q05D32, Q07800, Q07949, Q08BB5, Q09695, Q1RMV9, Q20432, Q28HW9, Q29I63, Q3B7T6, Q3KQB6, Q3TP92, Q3ZCQ8, Q4I099, Q4PEW9, Q4WI16, Q54GB2, Q59W44, Q5B4P0, Q5F3Z7, Q5RAJ8, Q5S7T7, Q5U395, Q5U3T3, Q5XIK8, Q61C05, Q66KM5

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
CSNK2A1	“down-regulates activity”	CTDP1	phosphorylation
CSNK2A2	“down-regulates activity”	CTDP1	phosphorylation
CSNK2B	“down-regulates activity”	CTDP1	phosphorylation
CTDP1	“down-regulates activity”	MASTL	dephosphorylation
CTDP1	“down-regulates activity”	CDK1	dephosphorylation
CTDP1	“up-regulates activity”	WEE1	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
FGFR2 mutant receptor activation	12	207.6×	4e-26
Signaling by FGFR2 IIIa TM	13	177.6×	2e-26
Abortive elongation of HIV-1 transcript in the absence of Tat	14	158.0×	3e-27
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	14	129.8×	3e-26
RNA Pol II CTD phosphorylation and interaction with CE	14	129.8×	3e-26
FGFR2 alternative splicing	13	125.0×	2e-24
MicroRNA (miRNA) biogenesis	12	124.6×	1e-22
mRNA Capping	14	121.1×	7e-26

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	7	39.8×	5e-08
RNA polymerase II preinitiation complex assembly	5	25.6×	8e-05
positive regulation of transcription initiation by RNA polymerase II	5	25.6×	8e-05
transcription by RNA polymerase II	13	17.3×	8e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	302
Likely benign	308
Benign	70

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
5301	NM_004715.5(CTDP1):c.863+389C>T	Pathogenic

SpliceAI

4135 predictions. Top by Δscore:

Variant	Effect	Δscore
18:79680260:GG:G	donor_gain	1.0000
18:79680261:GG:G	donor_gain	1.0000
18:79695220:TGTA:T	acceptor_loss	1.0000
18:79695222:TA:T	acceptor_loss	1.0000
18:79695222:TAG:T	acceptor_gain	1.0000
18:79695223:A:AG	acceptor_gain	1.0000
18:79695223:A:T	acceptor_loss	1.0000
18:79695223:AGA:A	acceptor_gain	1.0000
18:79695223:AGAGC:A	acceptor_gain	1.0000
18:79695224:G:GA	acceptor_gain	1.0000
18:79695224:GA:G	acceptor_gain	1.0000
18:79695224:GAG:G	acceptor_gain	1.0000
18:79695224:GAGC:G	acceptor_gain	1.0000
18:79695224:GAGCG:G	acceptor_gain	1.0000
18:79695305:CCCA:C	donor_gain	1.0000
18:79695306:CCA:C	donor_gain	1.0000
18:79695309:G:GG	donor_gain	1.0000
18:79695973:GCAG:G	acceptor_loss	1.0000
18:79695974:CA:C	acceptor_loss	1.0000
18:79695975:A:AG	acceptor_gain	1.0000
18:79695975:A:T	acceptor_loss	1.0000
18:79695975:AG:A	acceptor_gain	1.0000
18:79695976:G:A	acceptor_loss	1.0000
18:79695976:G:GG	acceptor_gain	1.0000
18:79695976:GG:G	acceptor_gain	1.0000
18:79697852:A:AG	acceptor_gain	1.0000
18:79697852:AATT:A	acceptor_gain	1.0000
18:79697853:A:G	acceptor_gain	1.0000
18:79697853:ATT:A	acceptor_gain	1.0000
18:79697854:T:G	acceptor_gain	1.0000

AlphaMissense

6260 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:79695280:T:C	C124R	1.000
18:79696054:T:C	L159S	1.000
18:79697897:T:C	L177P	1.000
18:79697915:T:C	L183P	1.000
18:79697921:T:A	L185H	1.000
18:79697921:T:C	L185P	1.000
18:79697921:T:G	L185R	1.000
18:79697930:A:T	D188V	1.000
18:79697933:T:C	L189S	1.000
18:79697936:A:T	D190V	1.000
18:79697948:T:A	I194N	1.000
18:79704821:C:A	R226S	1.000
18:79704876:T:A	V244D	1.000
18:79704884:T:C	F247L	1.000
18:79704886:C:A	F247L	1.000
18:79704886:C:G	F247L	1.000
18:79704888:G:A	G248D	1.000
18:79710373:T:C	F267S	1.000
18:79710382:G:C	R270P	1.000
18:79710385:T:A	I271K	1.000
18:79710421:A:T	K283I	1.000
18:79710422:A:C	K283N	1.000
18:79710422:A:T	K283N	1.000
18:79710431:C:A	N286K	1.000
18:79710431:C:G	N286K	1.000
18:79710433:T:A	L287H	1.000
18:79710433:T:C	L287P	1.000
18:79712977:T:C	L290P	1.000
18:79712979:T:C	F291L	1.000
18:79712980:T:C	F291S	1.000

dbSNP variants (sampled 300 via entrez): RS1000042246 (18:79741294 A>G), RS1000049985 (18:79748166 A>G), RS1000080347 (18:79737962 T>C), RS1000100959 (18:79710716 T>A), RS1000147594 (18:79748375 A>G), RS1000164841 (18:79708204 C>G,T), RS1000180484 (18:79705299 T>C), RS1000195130 (18:79703963 A>G), RS1000226625 (18:79726822 C>G,T), RS1000259983 (18:79679718 G>A,C), RS1000282825 (18:79742991 A>G), RS1000299449 (18:79730801 G>A), RS1000364084 (18:79700941 T>C), RS1000387460 (18:79682777 A>C), RS1000512987 (18:79706145 C>A,T)

Disease associations

OMIM: gene MIM:604927 | disease phenotypes: MIM:604168, MIM:118220

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital cataracts-facial dysmorphism-neuropathy syndrome	Definitive	Autosomal recessive

Mondo (2): congenital cataracts-facial dysmorphism-neuropathy syndrome (MONDO:0011402), Charcot-Marie-Tooth disease (MONDO:0015626)

Orphanet (2): Congenital cataracts-facial dysmorphism-neuropathy syndrome (Orphanet:48431), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000164	Abnormality of the dentition
HP:0000347	Micrognathia
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000568	Microphthalmia
HP:0000639	Nystagmus
HP:0000763	Sensory neuropathy
HP:0000764	Peripheral axonal degeneration
HP:0000786	Primary amenorrhea
HP:0000815	Hypergonadotropic hypogonadism
HP:0000939	Osteoporosis
HP:0001171	Split hand
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001310	Dysmetria
HP:0001511	Intrauterine growth retardation
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001943	Hypoglycemia
HP:0001999	Abnormal facial shape
HP:0002059	Cerebral atrophy
HP:0002072	Chorea
HP:0002080	Intention tremor

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001757_1	Schizophrenia	3.000000e-07
GCST004070_22	Cerebrospinal P-tau181p levels	5.000000e-10
GCST004625_203	Monocyte count	8.000000e-09
GCST008810_97	Smoking initiation (ever regular vs never regular)	1.000000e-11
GCST009028_9	Adverse response to drug	4.000000e-07
GCST009391_1849	Metabolite levels	9.000000e-06
GCST009391_936	Metabolite levels	9.000000e-06
GCST90002393_625	Monocyte count	2.000000e-28
GCST90002394_427	Monocyte percentage of white cells	4.000000e-21

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004763	p-tau measurement
EFO:0005091	monocyte count
EFO:0005670	smoking initiation
EFO:0009658	adverse effect
EFO:0010413	triacylglycerol 52:1 measurement
EFO:0010401	triacylglycerol 46:1 measurement
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
C565822	Congenital Cataracts, Facial Dysmorphism, And Neuropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2279103	CTDP1		0.00	0

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
aflatoxin B2	increases methylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
bisphenol S	decreases methylation	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Cidofovir	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Clodronic Acid	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Ifosfamide	decreases expression	1
Ivermectin	decreases expression	1
Oxygen	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00271635	PHASE2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT01401257	PHASE2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02561702	PHASE2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02967679	PHASE2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT03124459	PHASE2	TERMINATED	Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
NCT03254199	PHASE2	TERMINATED	A Study to Assess the Safety and Effectiveness of FLX-787 in Subjects With Charcot-Marie-Tooth Disease Experiencing Muscle Cramps.
NCT03943290	PHASE2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT05777226	PHASE2	UNKNOWN	Research of SORD-CMT Natural History and Epalrestat Treatment
NCT06482437	PHASE2	COMPLETED	Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease
NCT01902940	Not specified	COMPLETED	Natural History in CCFDN and IBM Syndromes
NCT01289704	PHASE2/PHASE3	UNKNOWN	Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program for Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
NCT00541164	PHASE1/PHASE2	COMPLETED	Effects of Coenzyme Q10 on Charcot-Marie-Tooth Disease
NCT05361031	PHASE1/PHASE2	COMPLETED	The Safety and Tolerability of Engensis (VM202) in Patients With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)
NCT07223632	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Treatment of Charcot-Marie-Tooth Disease, Axonal, Type 2S (CMT2S) in an Individual Patient
NCT00149045	Not specified	COMPLETED	Follow up and Observation of Charcot Marie Tooth Disease in Families
NCT01193075	Not specified	RECRUITING	Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others
NCT01203085	Not specified	COMPLETED	Development of Charcot Marie Tooth Disease (CMT) Pediatric Scale for Children With CMT
NCT01455623	Not specified	COMPLETED	Development and Validation of a Disability Severity Index for CMT
NCT01918826	Not specified	UNKNOWN	Evaluation of the Analgesic Efficiency of the Transcutaneous Neurostimulation in the Charcot Syndrome Marie Tooth on the Pains of Lower Limbs
NCT02001038	Not specified	COMPLETED	Survey of Current Management of Orthopaedic Complications in CMT Patients
NCT02011204	Not specified	COMPLETED	Study of Electrical Impedance Myography (EIM) in ALS
NCT02194010	Not specified	COMPLETED	Disability Severity Scale (DSI) and Hereditary Motor and Sensory Neuropathy Overall Disability Scale (HMSN-R-ODS)
NCT02429947	Not specified	COMPLETED	An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients
NCT02532244	Not specified	COMPLETED	Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02788734	Not specified	COMPLETED	Patient Reported Outcomes Measures (PROM) in Carpal Tunnel Therapies in Patients With Inherited Neuropathies
NCT02979145	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Infant Scale (INC-6611)
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03460951	Not specified	COMPLETED	Diffusion Tensor Imaging in Chronic Inflammatory Demyelinating Polyneuropathy (PIDC)
NCT03715283	Not specified	COMPLETED	Change in MUNIX in Patients With CMT1A Undergoing a Home Ankle Strengthening Program Versus Standard of Care
NCT03782883	Not specified	COMPLETED	The Impact of Charcot-Marie-Tooth Disease in the Real World
NCT03810508	Not specified	TERMINATED	A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)
NCT03966287	Not specified	COMPLETED	Analysis of Pain and Quality of Life in Patients With Charcot-Marie-Tooth Neuropathy (CMT)
NCT04010188	Not specified	RECRUITING	A Registered Cohort Study on Charcot-Marie-Tooth Disease
NCT04283175	Not specified	COMPLETED	Validation Study of Posturology Platforms for Evaluating Postural Control of Hemiparetic and Neuro-muscular Patients
NCT04461613	Not specified	UNKNOWN	Physical Activity in Persons With Charcot-Marie-Tooth: Developing a Measurement Instrument
NCT04786522	Not specified	COMPLETED	Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
NCT04967716	Not specified	UNKNOWN	Genetics of Charcot-Marie-Tooth Dystrophy and Related Diseases
NCT04980807	Not specified	COMPLETED	Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls