CDC40
protein-codingcell division cycle 40, the group of Spliceosomal Bact complex|Spliceosomal P complex|WD repeat domain containing|NTC associated proteins|Spliceosomal C complex
Gene summary
Pre-mRNA splicing occurs in two sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp17 protein, which functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. It suggests that this protein may play a role in cell cycle progression. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~74.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0030259
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0030259
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CDC40 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015891.3. 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 | 4 | 4 | ||||
| missense | 1 | 50 | 1 | 52 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 51 | 5 | 0 | 57 |
Highest pathogenic variant AF is 0.0000043540676
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056975.1 | 15 | MANE Select | |
| Ensembl | ENSP00000304370.1 | 15 | MANE Select | |
| Ensembl | ENSP00000357926.1 | 15 | Standard | |
| Ensembl | ENSP00000357928.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Spliceosome - Homo sapiens (human)
- mRNA Processing
- Gene expression (Transcription)
- RNA Polymerase II Transcription
- Metabolism of RNA
Biological Process
- mRNA splicing, via spliceosome
- RNA export from nucleus
- mRNA export from nucleus
- RNA splicing
- mRNA 3'-end processing
Molecular Function
- RNA binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- spliceosomal complex
- U2-type catalytic step 2 spliceosome
- catalytic step 2 spliceosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368932
- Coding exons
- 15
- Length
- 74135
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125737
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.67 | 172 | 303 | 0.568 | 0.0000141 | 3819 |
| Missense (PolyPhen) | 40 | 105.62 | 0.3787 | 1326 | ||
| Synonymous | 0.680 | 94 | 103 | 0.915 | 0.00000472 | 1043 |
| Loss of Function | 4.60 | 5 | 33.9 | 0.147 | 0.00000159 | 431 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Associates with the spliceosome late in the splicing pathway and may function in the second step of pre-mRNA splicing. {ECO:0000269|PubMed:9830021}.;
Recessive Scores
- pRec
- 0.153
Intolerance Scores
- LoFtool
- 0.224
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.91
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |