PIKFYVE

Chr 2AD

phosphoinositide kinase, FYVE-type zinc finger containing

Also known as: FAB1, HEL37, PIP5K, PIP5K3, ZFYVE29

NCBI Gene: 200576ENSG00000115020UniProt: Q9Y2I7OMIM: 609414

PIKFYVE encodes a dual-specificity kinase that phosphorylates phosphatidylinositol species to regulate endosome maturation, lysosomal trafficking, and endomembrane homeostasis. Mutations cause corneal fleck dystrophy, an autosomal dominant disorder characterized by numerous small white flecks in all layers of the corneal stroma due to keratocytes distended with lipid and mucopolysaccharide-filled vacuoles. The gene is highly constrained against loss-of-function variants, indicating it is essential for normal cellular function.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismADLOEUF 0.391 OMIM phenotype
Clinical Summary— PIKFYVE
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 298 VUS of 546 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.000
Z-score 7.15
OE 0.29 (0.22–0.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.05Z-score
OE missense 0.83 (0.78–0.87)
928 obs / 1120.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.29 (0.22–0.39)
0≤0.351.4
Missense OE0.83 (0.78–0.87)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 35 / 119.2Missense obs/exp: 928 / 1120.8Syn Z: 0.12

ClinVar Variant Classifications

546 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic14
VUS298
Likely Benign51
Benign88
Conflicting10
38
Pathogenic
14
Likely Pathogenic
298
VUS
51
Likely Benign
88
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
28
0
38
Likely Pathogenic
14
0
0
0
14
VUS
1
234
57
6
298
Likely Benign
0
15
10
26
51
Benign
0
17
42
29
88
Conflicting
—10
Total2426713761499

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

View in ClinVar →

Protein Context — Lollipop Plot

PIKFYVE · 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
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 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