PIP4K2A

Chr 10

phosphatidylinositol-5-phosphate 4-kinase type 2 alpha

Also known as: PI5P4KA, PIP5K2A, PIP5KII-alpha, PIP5KIIA, PIPK

This enzyme catalyzes the phosphorylation of phosphatidylinositol 5-phosphate to form phosphatidylinositol 4,5-bisphosphate, regulating phosphoinositide signaling pathways involved in autophagy, lysosome-peroxisome membrane contacts, and cellular lipid metabolism. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.56), suggesting some tolerance to complete gene loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
14
Pubs (1 yr)
9
P/LP submissions
0%
P/LP missense
0.56
LOEUF
Mechanism
Clinical SummaryPIP4K2A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 52 VUS of 86 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.142
Z-score 2.95
OE 0.27 (0.140.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.36Z-score
OE missense 0.75 (0.660.85)
178 obs / 236.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.140.56)
00.351.4
Missense OE0.75 (0.660.85)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 5 / 18.8Missense obs/exp: 178 / 236.8Syn Z: -0.60

ClinVar Variant Classifications

86 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS52
Benign6
8
Pathogenic
1
Likely Pathogenic
52
VUS
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
50
2
0
52
Likely Benign
0
0
0
0
0
Benign
0
1
3
2
6
Total05114267

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PIP4K2A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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