PIP5K1C

Chr 19p13.3

phosphatidylinositol-4-phosphate 5-kinase type 1 gamma

Aliases:: PIP5Kgamma, KIAA0589, LCCS3
MANE:: ENST00000335312.8

OMIM: 606102 ↗NCBI: 23396 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

PIP5K1C · O60331

v62025-08-01

Predicted Aligned Error matrix for PIP5K1C — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

63.8/ 100

Low

668 residues

Confidence breakdown

Very high(≥ 90)39%
Confident(70–90)7%
Low(50–70)6%
Very low(< 50)48%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Arthrogryposis
BIALLELIC, autosomal or pseudoautosomal
DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

lethal congenital contracture syndrome 3
0.67
Lethal congenital contracture syndrome type 3
0.60
neurodevelopmental disorder
0.51
PIP5K1C-related neurodevelopmental disorder
0.46
hereditary disease
0.41
Intellectual disability
0.37
epilepsy
0.37
autoimmune disorder of central nervous system
0.36
neurodegenerative disease
0.24
Miyoshi muscular dystrophy 1
0.12

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma

Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:12422219, PubMed:22942276). PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (Probable). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Together with PIP5K1A, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (By similarity). Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport (By similarity). Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis (PubMed:12847086). Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2) (PubMed:12847086). Required for clathrin-coated pits assembly at the synapse (PubMed:17261850). Participates in cell junction assembly (PubMed:17261850). Modulates adherens junctions formation by facilitating CDH1/cadherin trafficking (PubMed:17261850). Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions (PubMed:12422219). Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins (PubMed:12422219). Required for uropodium formation and retraction of the cell rear during directed migration (By similarity). Has a role in growth factor-stimulated directional cell migration and adhesion (By similarity). Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor (PubMed:17635937). Negative regulator of T-cell activation and adhesion (By similarity). Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor (By similarity). Together with PIP5K1A has a role during embryogenesis and together with PIP5K1B may have a role immediately after birth (By similarity)