PIP5K1B

Chr 9

phosphatidylinositol-4-phosphate 5-kinase type 1 beta

Also known as: MSS4, STM7

NCBI Gene: 8395ENSG00000107242UniProt: O14986OMIM: 602745

The PIP5K1B protein catalyzes phosphorylation of phosphatidylinositol 4-phosphate to generate phosphatidylinositol 4,5-bisphosphate (PIP2), a critical lipid second messenger that regulates signal transduction, vesicle trafficking, actin cytoskeleton dynamics, and cell motility. This gene is not well-constrained against loss-of-function variants (LOEUF 0.814), and no established human disease associations have been reported in the current literature. The clinical significance of PIP5K1B variants in pediatric neurogenetic disorders remains to be determined.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.81
Clinical Summary— PIP5K1B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 unique Pathogenic / Likely Pathogenic· 85 VUS of 152 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.000
Z-score 2.35
OE 0.54 (0.36–0.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.48Z-score
OE missense 0.59 (0.52–0.67)
174 obs / 293.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.54 (0.36–0.81)
0≤0.351.4
Missense OE0.59 (0.52–0.67)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 16 / 29.9Missense obs/exp: 174 / 293.7Syn Z: 0.85
DN
0.6938th %ile
GOF
0.6444th %ile
LOF
0.3453th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

152 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic8
VUS85
Likely Benign4
Benign1
34
Pathogenic
8
Likely Pathogenic
85
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
32
0
34
Likely Pathogenic
0
0
8
0
8
VUS
0
70
15
0
85
Likely Benign
0
2
0
2
4
Benign
0
0
1
0
1
Total173562132

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

View in ClinVar →

Protein Context — Lollipop Plot

PIP5K1B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Identification and validation of M2 macrophage-related genes in endometriosis
Ding H et al.·Heliyon
2023
Screening of periodontitis-related diagnostic biomarkers based on weighted gene correlation network analysis and machine algorithms.
Ji J et al.·Technol Health Care
2022
Genomic Analysis Reveals Candidate Genes Underlying Sex-Linked Eyelid Coloboma, Feather Color Traits, and Climatic Adaptation in Huoyan Geese
Wen J et al.·Animals (Basel)
2023
Renal Dysfunction Induced by Sodium p-Perfluorous Nonenoxybenzenesulfonate in Mice: Insights from the Intrinsic Mechanisms of Proteinuria.
Lyu Y et al.·Environ Sci Technol
2025Functional
Integrated Analysis of Multiple Microarrays Based on Raw Data Identified Novel Gene Signatures in Recurrent Implantation Failure
Zeng H et al.·Front Endocrinol (Lausanne)
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients