ANKFY1

Chr 17

ankyrin repeat and FYVE domain containing 1

Also known as: ANKHZN, BTBD23, ZFYVE14

NCBI Gene: 51479ENSG00000185722UniProt: Q9P2R3OMIM: 607927

This protein regulates endosomal trafficking and fusion, serving as an effector of Rab5 and binding phosphatidylinositol 3-phosphate to control vesicle transport between early endosomes, the Golgi, and lysosomes. Mutations cause autosomal dominant neurodevelopmental disorder with impaired intellectual development, hypotonia, and behavioral abnormalities. The gene is highly constrained against loss-of-function mutations, indicating that ANKFY1 haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.31
Clinical Summary— ANKFY1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
4 unique Pathogenic / Likely Pathogenic· 74 VUS of 106 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.956
Z-score 5.74
OE 0.19 (0.12–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.46Z-score
OE missense 0.74 (0.69–0.80)
531 obs / 716.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.12–0.31)
0≤0.351.4
Missense OE0.74 (0.69–0.80)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 11 / 58.3Missense obs/exp: 531 / 716.6Syn Z: 1.02
DN
0.3495th %ile
GOF
0.5268th %ile
LOF
0.64top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.31

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS74
Likely Benign5
4
Pathogenic
74
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
0
0
0
VUS
0
70
4
0
74
Likely Benign
0
2
0
3
5
Benign
0
0
0
0
0
Total0728383

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

View in ClinVar →

Protein Context — Lollipop Plot

ANKFY1 · 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 1 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