PIP5K1A

Chr 1

phosphatidylinositol-4-phosphate 5-kinase type 1 alpha

NCBI Gene: 8394 ENSG00000143398 UniProt: Q99755 OMIM: 603275

Enables 1-phosphatidylinositol-4-phosphate 5-kinase activity and kinase binding activity. Involved in several processes, including activation of GTPase activity; focal adhesion assembly; and ruffle assembly. Located in several cellular components, including lamellipodium; nucleus; and ruffle membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.54

Clinical Summary— PIP5K1A

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 4 VUS of 40 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.002

Z-score 3.61

OE 0.33 (0.20–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.58Z-score

OE missense 0.60 (0.54–0.68)

199 obs / 330.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.33 (0.20–0.54)

0≤0.351.4

Missense OE?0.60 (0.54–0.68)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 11 / 33.6Missense obs/exp: 199 / 330.8Syn Z: 0.74

This gene — mechanism propensity

0.6259th %ile

GOF

0.5367th %ile

LOF

0.4332th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

40 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS4

Likely Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	1	0	1
VUS	0	4	4
Likely Benign	0	0	0
Benign	0	0	0
Total	1	4	5

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap PIP5K1A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →