CPSF3
cleavage and polyadenylation specific factor 3, the group of Cleavage and polyadenylation specific factor subunits|MBL fold containing DNA/RNA interacting subfamily|Endoribonucleases
Basic information
Region (hg38): 2:9423651-9473101
Links
Phenotypes
GenCC
Source:
- neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures (Limited), mode of inheritance: AR
- neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures (Limited), mode of inheritance: AR
- neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Neurodevelopmental disorder with microcephaly, hypotonia, and seizures | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Neurologic | 35121750 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (40 variants)
- not_provided (8 variants)
- Neurodevelopmental_disorder_with_microcephaly,_hypotonia,_nystagmus,_and_seizures (5 variants)
- Neurodevelopmental_disorder_with_hypotonia,_microcephaly,_and_seizures (2 variants)
- HP:0001252%3B_HP:0001776%3B_HP:0000252%3B_HP:0001270%3B_HP:0000592 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPSF3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016207.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 44 | 46 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 1 | 1 | 44 | 7 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CPSF3 | protein_coding | protein_coding | ENST00000238112 | 18 | 49534 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.03e-7 | 0.999 | 125673 | 0 | 75 | 125748 | 0.000298 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.61 | 178 | 375 | 0.475 | 0.0000190 | 4550 |
| Missense in Polyphen | 45 | 120 | 0.37499 | 1477 | ||
| Synonymous | 0.744 | 121 | 132 | 0.918 | 0.00000750 | 1235 |
| Loss of Function | 2.98 | 17 | 36.4 | 0.467 | 0.00000169 | 474 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000546 | 0.000543 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000112 | 0.000109 |
| Finnish | 0.0000476 | 0.0000462 |
| European (Non-Finnish) | 0.000330 | 0.000325 |
| Middle Eastern | 0.000112 | 0.000109 |
| South Asian | 0.000665 | 0.000653 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as mRNA 3'-end-processing endonuclease. Also involved in the histone 3'-end pre-mRNA processing. U7 snRNP- dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner. {ECO:0000269|PubMed:14749727, ECO:0000269|PubMed:15037765, ECO:0000269|PubMed:17128255, ECO:0000269|PubMed:18688255}.;
- Pathway
- mRNA surveillance pathway - Homo sapiens (human);mRNA Processing;Gene expression (Transcription);polyadenylation of mrna;RNA Polymerase II Transcription;Metabolism of RNA;Processing of Intronless Pre-mRNAs;Processing of Capped Intronless Pre-mRNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;mRNA Splicing - Major Pathway;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Mature mRNAs Derived from Intronless Transcripts;mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Intolerance Scores
- loftool
- 0.765
- rvis_EVS
- -0.56
- rvis_percentile_EVS
- 19.54
Haploinsufficiency Scores
- pHI
- 0.167
- hipred
- Y
- hipred_score
- 0.706
- ghis
- 0.705
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.967
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cpsf3
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Zebrafish Information Network
- Gene name
- cpsf3
- Affected structure
- head
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- mRNA splicing, via spliceosome;termination of RNA polymerase II transcription;mRNA polyadenylation;mRNA cleavage;mRNA 3'-end processing by stem-loop binding and cleavage;mRNA export from nucleus;mRNA 3'-end processing;RNA phosphodiester bond hydrolysis, endonucleolytic
- Cellular component
- nucleoplasm;mRNA cleavage and polyadenylation specificity factor complex
- Molecular function
- RNA binding;endoribonuclease activity;protein binding;5'-3' exonuclease activity;metal ion binding