PCID2
protein-codingPCI domain containing 2, the group of Transcription and export complex 2
Gene summary
This gene encodes a component of the TREX-2 complex (transcription and export complex 2), which regulates mRNA export from the nucleus. This protein regulates expression of Mad2 mitotic arrest deficient-like 1, a cell division checkpoint protein. This protein also interacts with and stabilizes Brca2 (breast cancer 2) protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PCID2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001127202.4. 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 | 1 | 1 | ||||
| missense | 37 | 1 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 46 | 1 | 1 | 48 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001120674.1 | 14 | MANE Select | |
| Ensembl | ENSP00000337405.4 | 14 | MANE Select | |
| RefSeq | NP_001120675.1 | 14 | Standard | |
| RefSeq | NP_001245142.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- posttranscriptional tethering of RNA polymerase II gene DNA at nuclear periphery
- transcription elongation from RNA polymerase II promoter
- poly(A)+ mRNA export from nucleus
- negative regulation of apoptotic process
- regulation of mRNA stability
Molecular Function
- double-stranded DNA binding
- RNA binding
- protein binding
Cellular Component
- cellular_component
- transcriptionally active chromatin
- transcription export complex 2
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000246505
- Coding exons
- 14
- Length
- 31139
- Individuals with no LoFs
- 125694
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 54
- Defined
- 125748
- p
- 0.000215
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 186 | 256 | 0.726 | 0.0000142 | 2993 |
| Missense (PolyPhen) | 33 | 53.917 | 0.61205 | 649 | ||
| Synonymous | 0.398 | 96 | 101 | 0.950 | 0.00000634 | 822 |
| Loss of Function | 1.22 | 23 | 30.2 | 0.761 | 0.00000162 | 349 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00035 | 0.00034 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for B-cell survival through the regulation of the expression of cell-cycle checkpoint MAD2L1 protein during B cell differentiation (By similarity). Component of the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3 (PubMed:22307388). The TREX-2 complex functions in docking export- competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket). TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery. Binds and stabilizes BRCA2 and is thus involved in the control of R-loop- associated DNA damage and transcription-associated genomic instability. R-loop accumulation does not increase in PCID2- depleted cells. {ECO:0000250, ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:24896180}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- LoFtool
- 0.262
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 17.75
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.940
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |