CTDP1
protein-codingCTD phosphatase subunit 1, the group of CTD family phosphatases
Gene summary
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. [provided by RefSeq, Feb 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~74.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011402
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0011402
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0011402
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011402
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal
Intervention: Endocrine; Pharmacogenomic; Renal
Rationale: In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In the instance of anesthesia, monitoring is indicated, (eg, for severe complications such as stridor, pulmonary edema, malignant hyperthermia, and seizures); Individuals may suffer severe rhabdomyolysis related to viral infections, and awareness may allow rapid management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CTDP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004715.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 207 | 8 | 217 | ||
| missense | 275 | 25 | 5 | 305 | ||
| nonsense | 1 | 5 | 6 | |||
| start loss | 0 | |||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 1 | 292 | 232 | 13 | 538 |
Highest pathogenic variant AF is 0.000005005062
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004706.3 | 13 | MANE Select | |
| Ensembl | ENSP00000484525.2 | 13 | MANE Select | |
| RefSeq | NP_001189433.1 | 12 | Standard | |
| RefSeq | NP_001305440.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ctdp1 | Danio rerio | Structure: head Quality: pointed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Disease
- Formation of the HIV-1 Early Elongation Complex
- Gene expression (Transcription)
- Formation of HIV-1 elongation complex containing HIV-1 Tat
- Tat-mediated elongation of the HIV-1 transcript
Biological Process
- transcription by RNA polymerase II
- transcription elongation from RNA polymerase II promoter
- protein dephosphorylation
- exit from mitosis
- positive regulation by host of viral transcription
Molecular Function
- TFIIF-class transcription factor complex binding
- phosphoprotein phosphatase activity
- protein binding
- RNA polymerase II CTD heptapeptide repeat phosphatase activity
- Tat protein binding
Cellular Component
- spindle pole
- nucleus
- nucleoplasm
- cytoplasm
- centrosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000299543
- Coding exons
- 13
- Length
- 74710
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.996 | 501 | 568 | 0.882 | 0.0000403 | 6141 |
| Missense (PolyPhen) | 171 | 249.17 | 0.68626 | 2750 | ||
| Synonymous | -1.50 | 293 | 262 | 1.12 | 0.0000220 | 1950 |
| Loss of Function | 3.86 | 13 | 39.0 | 0.333 | 0.00000237 | 432 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0.000081 | 0.000079 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:22692537}.;
- Disease
- DISEASE: 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). {ECO:0000269|PubMed:14517542}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.230
Intolerance Scores
- LoFtool
- 0.251
- RVIS EVS
- -0.84
- RVIS percentile EVS
- 11.48
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.955
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |