PAICS

phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase, the group of Purinosome

Basic information

Region (hg38): 4:56435741-56464578

Previous symbols: [ "PAIS" ]

Links

ENSG00000128050 ∙ NCBI:10606 ∙ OMIM:172439 ∙ HGNC:8587 ∙ Uniprot:P22234 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• PAICS deficiency (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Phosphoribosylaminoimidazole carboxylase deficiency	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; Gastrointestinal; Musculoskeletal; Pulmonary	31600779

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAICS gene.

• not_specified (27 variants)
• Phosphoribosylaminoimidazole_carboxylase_deficiency (3 variants)
• not_provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAICS gene is commonly pathogenic or not. These statistics are base on transcript: NM_001079524.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense	1	1	28			30
nonsense	1					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	1	28	1	0

Highest pathogenic variant AF is 0.001114124

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAICS	protein_coding	protein_coding	ENST00000399688	10	25628

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000279	0.985	122164	167	2316	124647	0.0100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	154	199	0.774	0.00000923	2786
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.171	0.150
Ashkenazi Jewish	0.00	0.00
East Asian	0.000562	0.000556
Finnish	0.0000483	0.0000464
European (Non-Finnish)	0.00110	0.000991
Middle Eastern	0.000562	0.000556
South Asian	0.000645	0.000588
Other	0.00549	0.00513

dbNSFP

Source: dbNSFP

• Pathway: Purine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Metabolism of nucleotides;Metabolism;Nucleobase biosynthesis;Purine nucleotides nucleosides metabolism;inosine-5,-phosphate biosynthesis;Purine ribonucleoside monophosphate biosynthesis;purine nucleotides <i>de novo</i> biosynthesis (Consensus)

Recessive Scores

• pRec: 0.211

Intolerance Scores

• loftool: 0.963
• rvis_EVS: 1.04
• rvis_percentile_EVS: 91.21

Haploinsufficiency Scores

• pHI: 0.890
• hipred: Y
• hipred_score: 0.743
• ghis: 0.444

Essentials

• essential_gene_CRISPR: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Paics

Zebrafish Information Network

• Gene name: paics
• Affected structure: iridophore
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: 'de novo' IMP biosynthetic process;purine nucleobase biosynthetic process;purine ribonucleoside monophosphate biosynthetic process
• Cellular component: cytoplasm;cytosol;membrane;extracellular exosome
• Molecular function: phosphoribosylaminoimidazole carboxylase activity;phosphoribosylaminoimidazolesuccinocarboxamide synthase activity;protein binding;ATP binding;identical protein binding;5-amino-4-imidazole carboxylate lyase activity;cadherin binding