PI4KA

phosphatidylinositol 4-kinase alpha, the group of Armadillo like helical domain containing|PI4KA lipid kinase complex

Basic information

Region (hg38): 22:20707691-20859417

Previous symbols: [ "PIK4CA" ]

Links

ENSG00000241973 ∙ NCBI:5297 ∙ OMIM:600286 ∙ HGNC:8983 ∙ Uniprot:P42356 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis (Moderate), mode of inheritance: AR
• polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis (Definitive), mode of inheritance: AR
• polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gastrointestinal defects and immunodeficiency syndrome 2; Neurodevelopmental disorder with spasticity, hypomyelinating leukodystrophy, and brain abnormalities; Spastic paraplegia 84, autosomal recessive	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	Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	25855803; 34415322

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PI4KA gene.

• not provided (3 variants)
• Spastic paraplegia 84, autosomal recessive (3 variants)
• Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis (3 variants)
• PI4KA-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PI4KA 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			1	47	12	60
missense	1	3	68	4		76
nonsense	1	3	1			5
start loss						0
frameshift	4	4	1			9
inframe indel	1			1	3	5
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1	10	4	15
non coding		1	29	18	102	150
Total	8	12	100	70	117

Highest pathogenic variant AF is 0.000132

Variants in PI4KA

This is a list of pathogenic ClinVar variants found in the PI4KA region.

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

Position	Type	Phenotype	Significance	ClinVar
22-20707880-C-T			Likely benign (Jul 10, 2018)
22-20707980-G-T			Benign (Jul 09, 2018)
22-20708278-G-A			Benign (Jul 14, 2018)
22-20708391-G-A			Benign (Jul 10, 2018)
22-20708409-G-A			Benign (Jul 09, 2018)
22-20709337-A-G			Likely benign (Dec 01, 2023)
22-20709384-G-A		Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis	Benign (Sep 05, 2021)
22-20709664-T-G			Benign (Oct 05, 2019)
22-20709687-A-AAT			Benign (Jul 09, 2018)
22-20709708-C-T			Benign (Oct 05, 2019)
22-20709769-C-T			Benign (Oct 05, 2019)
22-20709832-G-A			Benign (Jul 09, 2018)
22-20709921-TTGTC-T		Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis • Spastic paraplegia 84, autosomal recessive	Pathogenic (Apr 27, 2023)
22-20709939-A-T		PI4KA-related disorder	Uncertain significance (May 02, 2023)
22-20709982-C-T			Benign/Likely benign (Oct 01, 2023)
22-20710068-A-C		not specified	Benign (Jan 24, 2024)
22-20710099-C-T			Benign (Jul 09, 2018)
22-20710716-TC-T		Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis	Pathogenic (Jan 24, 2022)
22-20710746-G-A			Benign/Likely benign (May 01, 2023)
22-20710805-C-T		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
22-20710808-G-A		Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis	Likely pathogenic (Sep 16, 2022)
22-20710827-G-A			Likely benign (Sep 21, 2017)
22-20710847-T-C			Uncertain significance (Feb 01, 2023)
22-20710853-C-T		Inborn genetic diseases	Uncertain significance (Apr 28, 2022)
22-20710913-A-G			Benign (Jul 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PI4KA	protein_coding	protein_coding	ENST00000255882	55	151727

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.12e-12	1.00	125613	1	134	125748	0.000537

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.53	883	1.23e+3	0.717	0.0000752	13738
Missense in Polyphen		190	350.99	0.54132		3933
Synonymous	-0.243	505	498	1.01	0.0000332	4037
Loss of Function	6.53	43	120	0.357	0.00000651	1342

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00177	0.00177
Ashkenazi Jewish	0.000601	0.000595
East Asian	0.000654	0.000653
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000406	0.000404
Middle Eastern	0.000654	0.000653
South Asian	0.000432	0.000392
Other	0.000817	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol- 1,4,5,-trisphosphate. {ECO:0000269|PubMed:10101268, ECO:0000269|PubMed:23229899}.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Inositol Metabolism;Ectoderm Differentiation;D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis;Metabolism of lipids;Inositol phosphate metabolism;TCR;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;cell cycle: g2/m checkpoint;Phosphatidylinositol phosphate metabolism;Synthesis of PIPs at the ER membrane;Synthesis of PIPs at the Golgi membrane;PI Metabolism;Phospholipid metabolism;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.182

Intolerance Scores

• loftool: 0.684
• rvis_EVS: -4.02
• rvis_percentile_EVS: 0.18

Haploinsufficiency Scores

• pHI: 0.222
• hipred: Y
• hipred_score: 0.637
• ghis: 0.646

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pi4ka
• Phenotype: digestive/alimentary phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype; growth/size/body region phenotype; hematopoietic system phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: pi4kaa
• Affected structure: pectoral fin
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: phosphatidylinositol biosynthetic process;signal transduction;phosphorylation;viral RNA genome replication;multi-organism membrane organization;viral replication complex formation and maintenance;phosphatidylinositol phosphorylation;phosphatidylinositol-mediated signaling
• Cellular component: cytoplasm;cytosol;plasma membrane;focal adhesion;membrane;viral replication complex;Golgi-associated vesicle membrane;extracellular exosome
• Molecular function: 1-phosphatidylinositol 4-kinase activity;protein binding;ATP binding;kinase activity;cadherin binding