PIP4K2C

protein-coding

phosphatidylinositol-5-phosphate 4-kinase type 2 gamma

Gene summary

Enables 1-phosphatidylinositol-4-phosphate 5-kinase activity and identical protein binding activity. Involved in 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process; negative regulation of insulin receptor signaling pathway; and positive regulation of autophagosome assembly. Located in autophagosome and cytosol. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

PIP5K2C

MANE transcript

NM_024779.5

Inheritance

—

ClinVar variants

U:48

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr12:57,591,174-57,603,418

External References & Databases

Ensembl (ENSG00000166908)

Transcript & Mutation Effects

hg38 • Region Span ~12.2 kb

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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 PIP4K2C variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 41

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024779.5. 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
missense			44 clinvar			44
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	48	0	0	48

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024779.5	RefSeq	NP_079055.3	10	MANE Select
ENST00000354947.10	Ensembl	ENSP00000347032.5	10	MANE Select
NM_001146258.2	RefSeq	NP_001139730.1	10	Standard
NM_001146259.2	RefSeq	NP_001139731.1	10	Standard

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)
Regulation of Actin Cytoskeleton
D-<i>myo</i>-inositol (1,4,5)-trisphosphate biosynthesis

Biological Process

phosphatidylinositol biosynthetic process
regulation of autophagy
regulation of phosphatidylinositol 3-kinase signaling
phosphatidylinositol phosphorylation
positive regulation of autophagosome assembly

Molecular Function

ATP binding
1-phosphatidylinositol-5-phosphate 4-kinase activity
identical protein binding

Cellular Component

autophagosome
cytosol
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354947
Coding exons: 10
Length: 12242
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	185	251	0.738	0.0000136	2789
Missense (PolyPhen)		61	100.44	0.60731		1200
Synonymous	0.359	93	97.5	0.954	0.00000526	812
Loss of Function	2.49	8	20.0	0.400	0.00000108	230

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play an important role in the production of Phosphatidylinositol bisphosphate (PIP2), in the endoplasmic reticulum. {ECO:0000250}.;

Intolerance Scores

RVIS EVS: -0.45
RVIS percentile EVS: 24.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.888

Gene Damage Prediction

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