PIR
protein-codingpirin
Gene summary
This gene encodes a member of the cupin superfamily. The encoded protein is an Fe(II)-containing nuclear protein expressed in all tissues of the body and concentrated within dot-like subnuclear structures. Interactions with nuclear factor I/CCAAT box transcription factor as well as B cell lymphoma 3-encoded oncoprotein suggest the encoded protein may act as a transcriptional cofactor and be involved in the regulation of DNA transcription and replication. Alternatively spliced transcript variants have been described. [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 ~108.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PIR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001018109.3. 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 | 0 | |||||
| missense | 27 | 4 | 31 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 31 | 0 | 4 | 35 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001018119.1 | 9 | MANE Select | |
| Ensembl | ENSP00000369785.5 | 9 | MANE Select | |
| RefSeq | NP_003653.1 | 9 | Standard | |
| Ensembl | ENSP00000369786.3 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- y branching of actin filaments
- Digestion
- Digestion and absorption
Biological Process
- transcription by RNA polymerase II
- digestion
- monocyte differentiation
- oxidation-reduction process
- regulation of nucleic acid-templated transcription
Molecular Function
- transcription coregulator activity
- protein binding
- quercetin 2,3-dioxygenase activity
- metal ion binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380421
- Coding exons
- 9
- Length
- 108767
- Individuals with no LoFs
- 125681
- Homozygous LoFs
- 26
- Heterozygous LoFs
- 40
- Defined
- 125747
- p
- 0.000262
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.398 | 119 | 107 | 1.11 | 0.00000789 | 1895 |
| Missense (PolyPhen) | 42 | 37.599 | 1.117 | 700 | ||
| Synonymous | -0.0660 | 41 | 40.5 | 1.01 | 0.00000323 | 547 |
| Loss of Function | -0.603 | 13 | 10.9 | 1.20 | 7.35e-7 | 203 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00016 | 0.00012 | rare |
| Latino/Admixed American | 0.00045 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00029 | 0.00016 | rare |
| Finnish | 0.00081 | 0.00060 | rare |
| European (Non-Finnish) | 0.00025 | 0.00018 | rare |
| South Asian | 0.00090 | 0.00056 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional coregulator of NF-kappa-B which facilitates binding of NF-kappa-B proteins to target kappa-B genes in a redox-state-dependent manner. May be required for efficient terminal myeloid maturation of hematopoietic cells. Has quercetin 2,3-dioxygenase activity (in vitro). {ECO:0000269|PubMed:17288615, ECO:0000269|PubMed:20010624, ECO:0000269|PubMed:20711196, ECO:0000269|PubMed:23716661}.;
Recessive Scores
- pRec
- 0.289
Intolerance Scores
- LoFtool
- 0.847
- RVIS EVS
- 0.48
- RVIS percentile EVS
- 79.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.792
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |