RPIA

ribose 5-phosphate isomerase A

Basic information

Region (hg38): 2:88691672-88750929

Links

ENSG00000153574 ∙ NCBI:22934 ∙ OMIM:180430 ∙ HGNC:10297 ∙ Uniprot:P49247 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ribose-5-P isomerase deficiency (Moderate), mode of inheritance: AR
• ribose-5-P isomerase deficiency (Supportive), mode of inheritance: AR
• ribose-5-P isomerase deficiency (Strong), mode of inheritance: AR
• ribose-5-P isomerase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ribose 5-phosphate isomerase 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	Biochemical; Neurologic	14988808

ClinVar

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

• Deficiency of ribose-5-phosphate isomerase (3 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPIA gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	15	4	20
missense		2	33	2		37
nonsense	2	1				3
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region			4	3	1	8
non coding			16	14	3	33
Total	4	3	50	31	7

Highest pathogenic variant AF is 0.00000658

Variants in RPIA

This is a list of pathogenic ClinVar variants found in the RPIA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-88691682-C-A		Deficiency of ribose-5-phosphate isomerase	Uncertain significance (Jan 12, 2018)
2-88691702-C-T			Likely pathogenic (Apr 18, 2023)
2-88691703-A-G		Deficiency of ribose-5-phosphate isomerase	Conflicting classifications of pathogenicity (May 21, 2021)
2-88691708-C-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
2-88691709-C-T			Uncertain significance (Jan 03, 2022)
2-88691710-C-A			Likely benign (Aug 05, 2023)
2-88691710-C-G			Likely benign (Mar 10, 2023)
2-88691710-C-T			Likely benign (Nov 08, 2022)
2-88691714-C-T		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
2-88691725-C-T			Likely benign (Aug 13, 2022)
2-88691753-C-A		Deficiency of ribose-5-phosphate isomerase	Uncertain significance (Jan 12, 2018)
2-88691755-C-T		Deficiency of ribose-5-phosphate isomerase	Conflicting classifications of pathogenicity (Aug 09, 2022)
2-88691770-C-G			Likely benign (Jan 26, 2023)
2-88691772-C-G			Uncertain significance (Nov 28, 2021)
2-88691782-C-T			Benign (Nov 01, 2023)
2-88691791-G-A			Likely benign (Jul 15, 2022)
2-88691804-C-A		RPIA-related disorder	Benign/Likely benign (Dec 11, 2023)
2-88691819-G-T			Uncertain significance (Mar 22, 2022)
2-88691841-A-G		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
2-88691844-C-T		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
2-88691851-C-T			Likely benign (Sep 21, 2023)
2-88691852-C-T			Uncertain significance (Jun 13, 2022)
2-88691875-C-T		Deficiency of ribose-5-phosphate isomerase	Uncertain significance (Jan 13, 2018)
2-88691891-T-TC			Pathogenic (Jan 24, 2024)
2-88691895-A-G			Uncertain significance (May 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPIA	protein_coding	protein_coding	ENST00000283646	9	59291

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000143	0.967	124780	0	17	124797	0.0000681

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.959	147	184	0.801	0.00000967	2017
Missense in Polyphen		36	62.249	0.57832		708
Synonymous	-0.560	77	71.0	1.08	0.00000379	618
Loss of Function	1.91	9	17.7	0.510	0.00000107	168

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000184	0.000184
Ashkenazi Jewish	0.00	0.00
East Asian	0.000119	0.000111
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000468	0.0000441
Middle Eastern	0.000119	0.000111
South Asian	0.000134	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Ribose 5-phosphate isomerase deficiency (RPID) [MIM:608611]: A patient has been described with a deficiency of ribose 5-phosphate isomerase who presented with leukoencephalopathy and peripheral neuropathy. Proton magnetic resonance spectroscopy of the brain revealed a highly elevated level of the polyols ribitol and D-arabitol, which were subsequently also found in high concentrations in body fluids. Deficient activity of RPIA, one of the pentose phosphate pathway enzymes, has been demonstrated in fibroblasts. {ECO:0000269|PubMed:14988808}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pentose phosphate pathway - Homo sapiens (human);Warburg Effect;Pentose Phosphate Pathway;Glucose-6-phosphate dehydrogenase deficiency;Ribose-5-phosphate isomerase deficiency;Transaldolase deficiency;Pentose Phosphate Pathway;Pentose phosphate pathway (hexose monophosphate shunt);Metabolism of carbohydrates;Metabolism;Pentose phosphate cycle;pentose phosphate pathway (non-oxidative branch);pentose phosphate pathway (Consensus)

Recessive Scores

• pRec: 0.461

Intolerance Scores

• loftool: 0.485
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.586
• hipred: N
• hipred_score: 0.455
• ghis: 0.584

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rpia
• 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: D-ribose metabolic process;pentose-phosphate shunt;pentose-phosphate shunt, non-oxidative branch
• Cellular component: cytosol;intracellular membrane-bounded organelle
• Molecular function: ribose-5-phosphate isomerase activity;protein binding;identical protein binding;monosaccharide binding