PICALM

Chr 11

phosphatidylinositol binding clathrin assembly protein

Also known as: CALM, CLTH, LAP

NCBI Gene: 8301ENSG00000073921UniProt: Q13492OMIM: 603025

This protein is a cytoplasmic adapter that recruits clathrin and AP-2 to plasma membranes for clathrin-mediated endocytosis and regulates clathrin-coated vesicle size and maturation, playing critical roles in synaptic transmission and autophagy. Somatic mutations cause acute myeloid leukemia, while the gene is highly constrained against loss-of-function variants in the general population. The gene shows autosomal inheritance patterns for constitutional variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 0.231 OMIM phenotype
Clinical Summary— PICALM
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 67 VUS of 165 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
0.23LOEUF
pLI 0.999
Z-score 4.85
OE 0.09 (0.04–0.23)
Highly constrained

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

Missense Constraint
1.45Z-score
OE missense 0.78 (0.70–0.86)
258 obs / 332.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.09 (0.04–0.23)
0≤0.351.4
Missense OE0.78 (0.70–0.86)
0≤0.61.4
Synonymous OE1.08
0≤1.21.6
LoF obs/exp: 3 / 33.1Missense obs/exp: 258 / 332.5Syn Z: -0.67
DN
0.3892th %ile
GOF
0.4382th %ile
LOF
0.69top 10%

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

LOFprediction above median · LOEUF 0.23

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

165 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS67
Likely Benign6
Benign39
20
Pathogenic
1
Likely Pathogenic
67
VUS
6
Likely Benign
39
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
1
0
1
VUS
1
56
10
0
67
Likely Benign
0
2
2
2
6
Benign
0
0
33
6
39
Total158668133

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

View in ClinVar →

Protein Context — Lollipop Plot

PICALM · 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
Exploring the interaction of APOE-ε4and PICALM rs3851179 with dynamic functional connectivity in healthy middle-aged adults at risk for Alzheimer's disease.
Dharia SY et al.·J Neural Eng
2026Functional
Picalm coordinates clathrin-mediated endocytosis and actin remodeling during myogenesis.
Gaugel J et al.·Mol Metab
2026Open AccessFunctional
Precursor B-Cell Acute Lymphoblastic Leukemia With PICALM∶∶MLLT10 Fusion Gene Positivity:Report of One Case and Literature Review.
Zhao JJ et al.·Zhongguo Yi Xue Ke Xue Yuan Xue Bao
2026Review
PICALM Genetic Variant Alters mRNA Expression Without Affecting Protein Levels or Tau Spreading in Alzheimer's Disease.
Ando K et al.·Cells
2026Open Access
Clonal Evolution and Lineage Switch from T-Cell Acute Lymphoblastic Leukemia to Acute Myeloid Leukemia in Therapy-Resistant PICALM::MLLT10 Leukemia.
Kawamura M et al.·EJHaem
2026Open Access
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