PIK3R5

phosphoinositide-3-kinase regulatory subunit 5

Basic information

Region (hg38): 17:8878910-8965712

Links

ENSG00000141506 ∙ NCBI:23533 ∙ OMIM:611317 ∙ HGNC:30035 ∙ Uniprot:Q8WYR1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ataxia-oculomotor apraxia 3	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	Neurologic	22065524

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIK3R5 gene.

• Inborn genetic diseases (37 variants)
• Ataxia with oculomotor apraxia type 3 (21 variants)
• not provided (19 variants)
• not specified (11 variants)
• Spastic ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIK3R5 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				7	5	12
missense			40	2	2	44
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3		11	14
Total	0	0	44	9	18

Variants in PIK3R5

This is a list of pathogenic ClinVar variants found in the PIK3R5 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-8880656-T-C		not specified	Uncertain significance (Mar 01, 2024)
17-8880691-A-C		not specified	Uncertain significance (Mar 01, 2024)
17-8880725-G-A		not specified • Ataxia with oculomotor apraxia type 3	Conflicting classifications of pathogenicity (Apr 01, 2024)
17-8880727-G-A		Ataxia with oculomotor apraxia type 3	Uncertain significance (Oct 07, 2022)
17-8880728-T-C			Uncertain significance (Sep 05, 2017)
17-8880752-T-C		not specified	Uncertain significance (Jul 08, 2021)
17-8880832-T-C		Ataxia with oculomotor apraxia type 3	Benign (Sep 05, 2021)
17-8880974-C-G		not specified	Uncertain significance (Aug 15, 2023)
17-8880975-C-T		Ataxia with oculomotor apraxia type 3	Uncertain significance (Feb 05, 2020)
17-8881044-A-G		Ataxia with oculomotor apraxia type 3	Benign (Sep 05, 2021)
17-8881651-T-C		PIK3R5-related disorder	Likely benign (Mar 26, 2019)
17-8881658-T-C		Ataxia with oculomotor apraxia type 3	Uncertain significance (Apr 29, 2022)
17-8881668-TCAC-T		Ataxia with oculomotor apraxia type 3	Uncertain significance (Oct 03, 2022)
17-8881691-G-A		not specified	Uncertain significance (Aug 22, 2023)
17-8881770-A-C		not specified • Ataxia with oculomotor apraxia type 3	Benign (Sep 05, 2021)
17-8881775-C-T		not specified • Ataxia with oculomotor apraxia type 3	Benign (Sep 05, 2021)
17-8881806-G-A			Uncertain significance (Feb 06, 2017)
17-8881828-G-A			Likely benign (Aug 01, 2023)
17-8881831-G-A			Likely benign (Mar 30, 2018)
17-8881880-C-A		not specified	Uncertain significance (Mar 22, 2024)
17-8884697-C-T			Benign (Apr 10, 2018)
17-8884758-G-C		not specified	Uncertain significance (Dec 01, 2022)
17-8886280-G-A		not specified	Uncertain significance (Oct 30, 2023)
17-8886295-T-C		not specified	Uncertain significance (Dec 18, 2023)
17-8886297-G-A		not specified	Uncertain significance (Mar 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIK3R5	protein_coding	protein_coding	ENST00000447110	18	86797

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.300	0.700	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.86	352	539	0.653	0.0000336	5626
Missense in Polyphen		74	170.8	0.43326		1755
Synonymous	1.49	202	231	0.875	0.0000142	1851
Loss of Function	4.70	10	43.4	0.231	0.00000216	473

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000869	0.0000869
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000489	0.0000462
European (Non-Finnish)	0.000103	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.000139	0.000131
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG (By similarity). {ECO:0000250}.
• Disease: DISEASE: Ataxia-oculomotor apraxia 3 (AOA3) [MIM:615217]: An autosomal recessive disease characterized by cerebellar ataxia, oculomotor apraxia, areflexia and peripheral neuropathy. {ECO:0000269|PubMed:22065524}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Platelet activation - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Regulation of toll-like receptor signaling pathway;Type II diabetes mellitus;Extracellular vesicle-mediated signaling in recipient cells;Chemokine signaling pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Regulation of Actin Cytoskeleton;ErbB Signaling Pathway;DNA Damage Response (only ATM dependent);Toll-like Receptor Signaling Pathway;Signaling by GPCR;Signal Transduction;Metabolism of lipids;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;GPVI-mediated activation cascade;Platelet activation, signaling and aggregation;Hemostasis;Synthesis of PIPs at the plasma membrane;PI Metabolism;Phospholipid metabolism;G beta:gamma signalling through PI3Kgamma;G-protein beta:gamma signalling;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.227
• rvis_EVS: -0.46
• rvis_percentile_EVS: 23.66

Haploinsufficiency Scores

• pHI: 0.0917
• hipred: Y
• hipred_score: 0.694
• ghis: 0.552

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.503

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pik3r5
• Phenotype: cellular phenotype; hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;phosphatidylinositol 3-kinase signaling;positive regulation of phosphatidylinositol 3-kinase signaling;platelet activation;positive regulation of MAP kinase activity;regulation of phosphatidylinositol 3-kinase activity;phosphatidylinositol phosphorylation;positive regulation of protein kinase B signaling
• Cellular component: nucleus;cytoplasm;microtubule organizing center;cytosol;plasma membrane;phosphatidylinositol 3-kinase complex;phosphatidylinositol 3-kinase complex, class IB;membrane
• Molecular function: G-protein beta/gamma-subunit complex binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity;1-phosphatidylinositol-3-kinase regulator activity