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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 12.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_018425.4	NP_060895.1	9	yes	-
ENST00000370631.4	ENSP00000359665.3	9	yes	-
ENST00000880057.1	ENSP00000550116.1	8	-	-
ENST00000880058.1	ENSP00000550117.1	7	-	-

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.

• not_specified (45 variants)
• Neurodevelopmental_disorder_with_hyperkinetic_movements,_seizures,_and_structural_brain_abnormalities (2 variants)

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. These statistics are base on transcript: NM_018425.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			47			47
nonsense	2		1			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	0	48	0	0

Highest pathogenic variant AF is 0.0000020681669

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
		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

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

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