PAICS
protein-codingphosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase, the group of Purinosome
Gene summary
This gene encodes a bifunctional enzyme containing phosphoribosylaminoimidazole carboxylase activity in its N-terminal region and phosphoribosylaminoimidazole succinocarboxamide synthetase in its C-terminal region. It catalyzes steps 6 and 7 of purine biosynthesis. The gene is closely linked and divergently transcribed with a locus that encodes an enzyme in the same pathway, and transcription of the two genes is coordinately regulated. The human genome contains several pseudogenes of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
- PAIS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859003
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0859003
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Gastrointestinal; Musculoskeletal; Pulmonary
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PAICS variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001079524.2. 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 | 2 | 36 | 1 | 39 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 1 | 3 | 39 | 2 | 0 | 45 |
Highest pathogenic variant AF is 0.001114124
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001072992.1 | 9 | MANE Select | |
| Ensembl | ENSP00000421096.1 | 9 | MANE Select | |
| RefSeq | NP_001072993.1 | 10 | Standard | |
| RefSeq | NP_001378939.1 | 15 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| paics | Danio rerio | Structure: iridophore Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Purine metabolism - Homo sapiens (human)
- Purine Nucleoside Phosphorylase Deficiency
- Mercaptopurine Action Pathway
- Azathioprine Action Pathway
- Xanthine Dehydrogenase Deficiency (Xanthinuria)
Biological Process
- 'de novo' IMP biosynthetic process
- purine nucleobase biosynthetic process
- purine ribonucleoside monophosphate biosynthetic process
Molecular Function
- phosphoribosylaminoimidazole carboxylase activity
- phosphoribosylaminoimidazolesuccinocarboxamide synthase activity
- protein binding
- ATP binding
- identical protein binding
Cellular Component
- cytoplasm
- cytosol
- membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000399688
- Coding exons
- 10
- Length
- 25628
- Individuals with no LoFs
- 122164
- Homozygous LoFs
- 167
- Heterozygous LoFs
- 2316
- Defined
- 124647
- p
- 0.0100
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.13 | 154 | 199 | 0.774 | 0.00000923 | 2786 |
| Missense (PolyPhen) | 58 | 81.605 | 0.71074 | 1151 | ||
| Synonymous | -0.0193 | 69 | 68.8 | 1.00 | 0.00000322 | 808 |
| Loss of Function | 2.18 | 11 | 22.1 | 0.499 | 0.00000123 | 276 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.16 | 0.14 | notable |
| Latino/Admixed American | 0.0089 | 0.0081 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00056 | 0.00056 | rare |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.0011 | 0.00099 | notable |
| South Asian | 0.00064 | 0.00059 | rare |
| Other | 0.0055 | 0.0051 | notable |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.211
Intolerance Scores
- LoFtool
- 0.963
- RVIS EVS
- 1.04
- RVIS percentile EVS
- 91.21
Essentials
- Essential (CRISPR)
- E
- 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 |