PIP4K2A

protein-coding

phosphatidylinositol-5-phosphate 4-kinase type 2 alpha

Gene summary

Phosphatidylinositol-5,4-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. [provided by RefSeq, Jul 2008]

Previous symbols:

PIP5K2A

MANE transcript

NM_005028.5

Inheritance

—

ClinVar variants

U:61B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr10:22,534,854-22,714,578

External References & Databases

Ensembl (ENSG00000150867)

Transcript & Mutation Effects

hg38 • Region Span ~179.7 kb

Loading mutation effect viewer...

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 PIP4K2A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005028.5. 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			2 clinvar		2 clinvar	4
missense			53 clinvar		1 clinvar	54
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	61	0	3	64

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005028.5	RefSeq	NP_005019.2	10	MANE Select
ENST00000376573.9	Ensembl	ENSP00000365757.4	10	MANE Select
NM_001330062.2	RefSeq	NP_001316991.1	9	Standard
ENST00000323883.11	Ensembl	ENSP00000326294.7	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pip4k2aa	Danio rerio	Structure: head Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

pip4k2aa

Danio rerio

Structure: head

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
Phosphatidylinositol Phosphate Metabolism
Joubert syndrome

Biological Process

phospholipid metabolic process
phosphatidylinositol biosynthetic process
regulation of autophagy
regulation of phosphatidylinositol 3-kinase signaling
megakaryocyte development

Molecular Function

ATP binding
1-phosphatidylinositol-4-phosphate 5-kinase activity
1-phosphatidylinositol-5-phosphate 4-kinase activity
1-phosphatidylinositol-3-phosphate 4-kinase activity

Cellular Component

nucleoplasm
autophagosome
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376573
Coding exons: 10
Length: 179707
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.36	178	237	0.752	0.0000130	2714
Missense (PolyPhen)		35	75.582	0.46308		885
Synonymous	-0.598	102	94.6	1.08	0.00000595	730
Loss of Function	2.95	5	18.8	0.266	8.88e-7	248

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the phosphorylation of phosphatidylinositol 5- phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2. May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation. May negatively regulate insulin- stimulated glucose uptake by lowering the levels of PtdIns5P. May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size. {ECO:0000269|PubMed:18364242}.;

Recessive Scores

pRec: 0.212

Intolerance Scores

LoFtool: 0.301
RVIS EVS: -0.03
RVIS percentile EVS: 51.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.702

Gene Damage Prediction

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