PIP4K2A

phosphatidylinositol-5-phosphate 4-kinase type 2 alpha

Basic information

Region (hg38): 10:22534853-22714578

Previous symbols: [ "PIP5K2A" ]

Links

ENSG00000150867 ∙ NCBI:5305 ∙ OMIM:603140 ∙ HGNC:8997 ∙ Uniprot:P48426 ∙ 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 PIP4K2A gene.

• Inborn genetic diseases (16 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIP4K2A 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					2	2
missense			16		1	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	16	0	5

Variants in PIP4K2A

This is a list of pathogenic ClinVar variants found in the PIP4K2A region.

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

Position	Type	Phenotype	Significance	ClinVar
10-22537235-C-T		not specified	Uncertain significance (Dec 19, 2023)
10-22537249-T-C			Benign (Oct 09, 2017)
10-22537255-G-T		not specified	Uncertain significance (Sep 16, 2021)
10-22541831-C-T		not specified	Uncertain significance (Jan 08, 2024)
10-22541839-G-C		not specified	Uncertain significance (Oct 06, 2021)
10-22541861-G-T			Benign (Dec 13, 2018)
10-22541914-G-T		not specified	Uncertain significance (Oct 12, 2021)
10-22541923-C-G		not specified	Uncertain significance (Nov 07, 2022)
10-22541928-G-A			Benign (Oct 09, 2017)
10-22541933-C-T		not specified	Uncertain significance (Oct 04, 2022)
10-22541950-T-C		not specified	Uncertain significance (Feb 22, 2023)
10-22541993-C-G		not specified	Uncertain significance (Jul 12, 2023)
10-22550154-G-A			Benign (Aug 23, 2019)
10-22573343-G-A		not specified	Uncertain significance (Feb 11, 2022)
10-22591649-T-C		not specified	Uncertain significance (Jul 09, 2021)
10-22591745-A-T		not specified	Uncertain significance (Feb 10, 2022)
10-22591760-G-A		not specified	Uncertain significance (Nov 08, 2022)
10-22607917-C-T			Benign (Oct 09, 2017)
10-22607998-A-C		not specified	Uncertain significance (Dec 14, 2023)
10-22609676-C-T		not specified	Uncertain significance (Nov 10, 2022)
10-22714185-A-C		not specified	Uncertain significance (Aug 12, 2022)
10-22714199-C-A		not specified	Uncertain significance (Jul 09, 2021)
10-22714263-G-T		not specified	Uncertain significance (Dec 08, 2023)
10-22714296-C-G		not specified	Uncertain significance (Apr 27, 2022)
10-22714301-G-A		not specified	Uncertain significance (Jul 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIP4K2A	protein_coding	protein_coding	ENST00000376573	10	179707

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.142	0.858	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.36	178	237	0.752	0.0000130	2714
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000623	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Signal Transduction;Gene expression (Transcription);Synthesis of PIPs in the nucleus;Generic Transcription Pathway;Metabolism of lipids;Inositol phosphate metabolism;RNA Polymerase II Transcription;PI5P Regulates TP53 Acetylation;Metabolism;D-<i>myo</i>-inositol-5-phosphate metabolism;superpathway of inositol phosphate compounds;BCR;Phosphatidylinositol phosphate metabolism;PIP3 activates AKT signaling;Synthesis of PIPs at the plasma membrane;Regulation of TP53 Activity through Acetylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;PI Metabolism;Phospholipid metabolism;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.212

Intolerance Scores

• loftool: 0.301
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.66

Haploinsufficiency Scores

• pHI: 0.140
• hipred: Y
• hipred_score: 0.748
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.702

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pip4k2a
• Phenotype: growth/size/body region 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); normal phenotype; neoplasm

Zebrafish Information Network

• Gene name: pip4k2aa
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: phospholipid metabolic process;phosphatidylinositol biosynthetic process;regulation of autophagy;regulation of phosphatidylinositol 3-kinase signaling;megakaryocyte development;phosphatidylinositol phosphorylation;positive regulation of autophagosome assembly
• Cellular component: nucleoplasm;autophagosome;cytosol;plasma membrane
• 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