PI4K2A

phosphatidylinositol 4-kinase type 2 alpha

Basic information

Region (hg38): 10:97640671-97676434

Links

ENSG00000155252 ∙ NCBI:55361 ∙ OMIM:609763 ∙ HGNC:30031 ∙ Uniprot:Q9BTU6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities	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	Craniofacial; Musculoskeletal; Neurologic	30564627; 32418222; 35880319

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PI4K2A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PI4K2A 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						0
missense			18			18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	0	0

Variants in PI4K2A

This is a list of pathogenic ClinVar variants found in the PI4K2A region.

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

Position	Type	Phenotype	Significance	ClinVar
10-97640746-G-A		not specified	Uncertain significance (Jun 23, 2023)
10-97640786-C-T		not specified	Uncertain significance (Jan 19, 2022)
10-97640807-C-A		Neurodevelopmental disorder with hyperkinetic movements, seizures, and structural brain abnormalities	Pathogenic (Feb 29, 2024)
10-97640921-C-T		not specified	Uncertain significance (Aug 10, 2021)
10-97640948-C-T		not specified	Uncertain significance (Oct 05, 2023)
10-97640996-C-T		not specified	Uncertain significance (Aug 02, 2022)
10-97640999-C-T		not specified	Uncertain significance (Apr 29, 2024)
10-97641105-C-G		not specified	Uncertain significance (May 07, 2024)
10-97641169-C-T		not specified	Uncertain significance (May 03, 2023)
10-97650941-A-G		not specified	Uncertain significance (Sep 29, 2022)
10-97650990-T-G		not specified	Uncertain significance (Nov 15, 2021)
10-97651134-G-A		not specified	Uncertain significance (Mar 01, 2023)
10-97656365-G-T		not specified	Uncertain significance (Apr 29, 2024)
10-97656843-T-C		not specified	Uncertain significance (Sep 07, 2022)
10-97656845-G-A		not specified	Uncertain significance (Jun 07, 2024)
10-97656887-G-A		not specified	Uncertain significance (Sep 01, 2021)
10-97656914-C-T		not specified	Uncertain significance (Dec 19, 2022)
10-97656926-C-G		not specified	Uncertain significance (Jan 11, 2023)
10-97656938-C-T		not specified	Uncertain significance (May 23, 2023)
10-97662909-C-T		Neurodevelopmental disorder with hyperkinetic movements, seizures, and structural brain abnormalities	Pathogenic (Feb 29, 2024)
10-97662948-A-G		not specified	Uncertain significance (May 08, 2024)
10-97662966-C-T		not specified	Uncertain significance (Dec 12, 2023)
10-97666533-G-A		not specified	Uncertain significance (Aug 12, 2021)
10-97673615-A-G		not specified	Uncertain significance (Apr 22, 2022)
10-97673650-A-G		not specified	Uncertain significance (Mar 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PI4K2A	protein_coding	protein_coding	ENST00000370631	9	92061

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.804	0.196	125738	0	8	125746	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.89	129	260	0.496	0.0000143	3086
Missense in Polyphen		30	97.665	0.30717		1194
Synonymous	1.97	77	102	0.752	0.00000522	960
Loss of Function	3.67	4	23.0	0.174	0.00000113	254

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Membrane-bound phosphatidylinositol-4 kinase (PI4- kinase) that catalyzes the phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a lipid that plays important roles in endocytosis, Golgi function, protein sorting and membrane trafficking and is required for prolonged survival of neurons. Besides, phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P) is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). {ECO:0000269|PubMed:11279162, ECO:0000269|PubMed:16443754, ECO:0000269|PubMed:20388919, ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:24675427, ECO:0000269|PubMed:25168678, ECO:0000305}.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Wnt Signaling Pathway;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Metabolism of lipids;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;Synthesis of PIPs at the Golgi membrane;Synthesis of PIPs at the early endosome membrane;Synthesis of PIPs at the plasma membrane;PI Metabolism;Phospholipid metabolism;Canonical Wnt signaling pathway (Consensus)

Intolerance Scores

• loftool: 0.102
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.38

Haploinsufficiency Scores

• pHI: 0.539
• hipred: Y
• hipred_score: 0.626
• ghis: 0.488

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.876

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pi4k2a
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism 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; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: basophil degranulation;phosphatidylinositol biosynthetic process;Golgi organization;endosome organization;phosphatidylinositol phosphorylation
• Cellular component: mitochondrion;lysosomal membrane;endosome;trans-Golgi network;cytosol;plasma membrane;integral component of plasma membrane;membrane;cell junction;dendrite;synaptic vesicle membrane;BLOC-1 complex;intrinsic component of membrane;cytoplasmic vesicle;early endosome membrane;growing cell tip;presynaptic membrane;neuron projection;neuronal cell body;perikaryon;host cell presynaptic membrane;membrane raft
• Molecular function: magnesium ion binding;1-phosphatidylinositol 4-kinase activity;protein binding;ATP binding;AP-3 adaptor complex binding