PIK3AP1

protein-coding

phosphoinositide-3-kinase adaptor protein 1

Gene summary

Predicted to enable phosphatidylinositol 3-kinase regulatory subunit binding activity and signaling receptor binding activity. Predicted to be involved in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; regulation of inflammatory response; and regulation of innate immune response. Predicted to be located in membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_152309.3

Inheritance

—

ClinVar variants

U:268B:160

Top phenotype

Infantile spasms

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr10:96,593,315-96,720,514

External References & Databases

Ensembl (ENSG00000155629)

Transcript & Mutation Effects

hg38 • Region Span ~127.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PIK3AP1 variants in ClinVar

6 Conditions Cataloged

Infantile spasmsTotal: 462

not specifiedTotal: 93

not providedTotal: 19

PIK3AP1-related disorderTotal: 14

PIK3AP1-Associated Seizure DisorderTotal: 1

PIK3AP1-related early onset epileptic encephalopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152309.3. 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 clinvar	122 clinvar	16 clinvar	139
missense			260 clinvar	17 clinvar	5 clinvar	282
nonsense			3 clinvar			3
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	268	139	21	428

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152309.3	RefSeq	NP_689522.2	17	MANE Select
ENST00000339364.10	Ensembl	ENSP00000339826.5	17	MANE Select
ENST00000371109.3	Ensembl	ENSP00000360150.3	10	Standard
ENST00000371109.4	Ensembl	ENSP00000360150.3	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

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

Molecular Function

phosphatidylinositol 3-kinase regulatory subunit binding
identical protein binding
phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Cellular Component

cytosol
plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339364
Coding exons: 17
Length: 127203
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125733
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.26	346	486	0.712	0.0000290	5274
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.0355
RVIS EVS: 0.05
RVIS percentile EVS: 57.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.298

Gene Damage Prediction

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