PIK3AP1

phosphoinositide-3-kinase adaptor protein 1

Basic information

Region (hg38): 10:96593314-96720514

Links

ENSG00000155629 ∙ NCBI:118788 ∙ OMIM:607942 ∙ HGNC:30034 ∙ Uniprot:Q6ZUJ8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIK3AP1 gene.

• Infantile spasms (353 variants)
• Inborn genetic diseases (30 variants)
• not provided (5 variants)
• PIK3AP1-Associated Seizure Disorder (1 variants)
• PIK3AP1-related early onset epileptic encephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIK3AP1 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			3	88	20	111
missense			174	8	8	190
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			11	9	2	22
non coding			1	33		34
Total	0	0	184	129	28

Variants in PIK3AP1

This is a list of pathogenic ClinVar variants found in the PIK3AP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-96595608-G-C		Infantile spasms	Uncertain significance (Jul 19, 2023)
10-96595608-G-T		Infantile spasms	Uncertain significance (Jun 27, 2022)
10-96595616-G-A		Infantile spasms	Benign (Oct 08, 2023)
10-96595617-G-A		Infantile spasms	Uncertain significance (Dec 18, 2023)
10-96595626-G-A		Infantile spasms	Uncertain significance (Jul 07, 2023)
10-96595628-C-T		Infantile spasms	Likely benign (Aug 27, 2022)
10-96595629-G-A		Infantile spasms	Uncertain significance (Jan 30, 2024)
10-96595651-G-T		Infantile spasms	Likely benign (Aug 23, 2022)
10-96602261-A-C		Infantile spasms	Likely benign (Aug 17, 2023)
10-96602261-A-G		Infantile spasms	Likely benign (Aug 06, 2022)
10-96602261-A-T		Infantile spasms	Likely benign (Dec 11, 2023)
10-96602265-C-A		Infantile spasms	Likely benign (Oct 23, 2022)
10-96602266-A-G		Infantile spasms	Likely benign (Jul 06, 2022)
10-96602274-T-C		Infantile spasms	Uncertain significance (Mar 15, 2020)
10-96602286-G-A		Infantile spasms	Uncertain significance (Sep 08, 2021)
10-96602288-G-A		Infantile spasms	Likely benign (Dec 01, 2023)
10-96602297-C-T		Infantile spasms	Benign (Jan 24, 2024)
10-96602298-G-A		Infantile spasms	Uncertain significance (Oct 03, 2023)
10-96602301-G-A		Infantile spasms	Uncertain significance (Sep 01, 2021)
10-96602303-C-T		Infantile spasms	Benign (Jan 25, 2024)
10-96602305-C-G		Infantile spasms	Uncertain significance (Sep 13, 2022)
10-96602305-C-T		Infantile spasms • not specified	Conflicting classifications of pathogenicity (Oct 16, 2023)
10-96602321-G-C		Infantile spasms	Likely benign (Mar 23, 2022)
10-96602323-G-A		Infantile spasms	Uncertain significance (Sep 01, 2021)
10-96602329-T-C		not specified	Likely benign (Oct 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIK3AP1	protein_coding	protein_coding	ENST00000339364	17	127203

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000431	125731	0	2	125733	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.26	346	486	0.712	0.0000290	5274
Missense in Polyphen		112	191.23	0.58568		2046
Synonymous	1.54	172	200	0.861	0.0000135	1576
Loss of Function	5.64	1	39.0	0.0256	0.00000194	460

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000883	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL. {ECO:0000269|PubMed:15893754}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);B Cell Receptor Signaling Pathway;PI3K-Akt Signaling Pathway;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Disease;Signal Transduction;Signaling by the B Cell Receptor (BCR);TCR;Immune System;Adaptive Immune System;PIP3 activates AKT signaling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;Intracellular signaling by second messengers;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.0355
• rvis_EVS: 0.05
• rvis_percentile_EVS: 57.48

Haploinsufficiency Scores

• pHI: 0.185
• hipred: Y
• hipred_score: 0.825
• ghis: 0.493

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.298

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pik3ap1
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: positive regulation of phosphatidylinositol 3-kinase signaling;toll-like receptor 2 signaling pathway;toll-like receptor 4 signaling pathway;toll-like receptor 7 signaling pathway;toll-like receptor 9 signaling pathway;phosphatidylinositol phosphorylation;regulation of inflammatory response;positive regulation of protein kinase B signaling
• Cellular component: cytosol;plasma membrane;membrane
• Molecular function: phosphatidylinositol 3-kinase regulatory subunit binding;identical protein binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity