PICALM — Phosphatidylinositol Binding Clathrin Assembly Protein
Pathway Diagram
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">PICALM — Phosphatidylinositol Binding Clathrin Assembly Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>PICALM</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Phosphatidylinositol Binding Clathrin Assembly Protein</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>10q24.2</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/81501" target="_blank">81501</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000021762" target="_blank">ENSG00000021762</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/610004" target="_blank">610004</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q7Z417" target="_blank">Q7Z417</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers-disease)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, Blood cells, Heart, Lung</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Variants</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">rs3851179 (protective, OR ~0.86)<br>rs5942 (risk)<br>rs12340882 (eQTL)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">109 edges</a></td>
</tr>
</table>
PICALM — Phosphatidylinositol Binding Clathrin Assembly Protein
Introduction
PICALM (Phosphatidylinositol Binding Clathrin Assembly Protein, also known as CALM or CLT) is a gene located on chromosome 10q24.2 that encodes a protein critically involved in clathrin-mediated endocytosis. First identified as a significant genetic risk factor for late-onset Alzheimer's disease (AD) in the landmark 2009 genome-wide association study (GWAS), alongside [CLU](/genes/clu) and CR1, PICALM remains one of the most consistently replicated AD risk loci [@harold2009][@lambert2009].
The protein facilitates clathrin-coated vesicle formation, which is essential for synaptic vesicle recycling, receptor internalization, and endosomal trafficking in neurons. Through these mechanisms, PICALM influences [amyloid precursor protein](/genes/app) (APP) processing, [amyloid-beta](/proteins/amyloid-beta) (Aβ) production, and synaptic function—all key processes in AD pathogenesis.
Gene Structure and Expression
Genomic Organization
The PICALM gene spans approximately 54 kb on chromosome 10q24.2 (coordinates: chr10:96,200,000-96,254,000, GRCh38). It consists of 21 exons encoding a 652-amino acid protein. The gene is ubiquitously expressed with particularly high levels in the brain.
Brain Expression
PICALM is highly expressed in the central nervous system:
- [Cerebral cortex](/brain-regions/cortex) — highest expression in pyramidal neurons of layers II-IV
- [Hippocampus](/brain-regions/hippocampus) — strong expression in CA1-CA3 pyramidal neurons and dentate gyrus
- Basal ganglia — moderate expression in striatal neurons
- Cerebellum — lower expression in Purkinje cells
Cellular Distribution
In the brain, PICALM is expressed in:
- [Neurons](/entities/neurons) — highest expression, particularly in excitatory pyramidal neurons
- [Astrocytes](/cell-types/astrocytes) — moderate expression
- [Microglia](/cell-types/microglia) — lower expression
- [Oligodendrocytes](/cell-types/oligodendrocytes) — variable expression
Expression data is available from the [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=PICALM).
Allen Brain Atlas Data
Gene Expression
PICALM (Phosphatidylinositol Binding Clathrin Assembly Protein) shows neuronal-enriched expression:
- Cerebral cortex - High in pyramidal neurons
- Hippocampus - High in CA regions and dentate gyrus
- Striatum - Moderate expression
- Cerebellum - Moderate in Purkinje cells
- Brain stem - Variable expression
Single-Cell Expression
Single-cell RNA-seq data from the Allen Brain Atlas shows:
- Excitatory neurons - Highest expression
- Inhibitory neurons - Moderate expression
- Astrocytes - Moderate expression
- Oligodendrocytes - Variable
- Microglia - Lower expression
Brain Region Expression Levels
| Region | Expression Level | Data Source |
|--------|-----------------|--------------|
| Cortex | Very High | Human MTG |
| Hippocampus | High | Mouse Brain |
| Striatum | Medium | Mouse Brain |
| Cerebellum | Medium | Mouse Brain |
External Resources
- [Allen Human Brain Atlas - PICALM](https://human.brain-map.org/microarray/search/show?search_term=PICALM)
- [Allen Mouse Brain Atlas - Picalm](https://mouse.brain-map.org/gene/show?gene_id=18534)
- [Allen Cell Type Atlas - PICALM](https://celltypes.brain-map.org/)
Protein Structure and Function
Domain Architecture
The PICALM protein contains several functional domains:
N-terminal Domain — Contains the phosphatidylinositol-4,5-bisphosphate (PIP2) binding site, which targets the protein to the plasma membrane
Central Region — Mediates interactions with clathrin and other endocytic proteins
Clathrin-Binding Domain — Facilitates recruitment and assembly of clathrin triskelions
C-terminal Region — Contains additional protein-protein interaction motifsPICALM/CALM functions as an accessory protein in clathrin-mediated endocytosis through multiple mechanisms:
Membrane Recruitment — The N-terminal domain binds to phosphatidylinositol-4,5-bisphosphate (PIP2) on the plasma membrane, targeting PICALM to sites of vesicle formation [@tebar1999].
Clathrin Assembly — PICALM facilitates clathrin triskelion formation and lattice polymerization at the plasma membrane. It serves as a scaffold that nucleates clathrin coat assembly [@cousin2001].
Vesicle Scission — Working with dynamin and other proteins, PICALM participates in the final scission step that releases clathrin-coated vesicles into the cytoplasm [@ryan2006].
Cargo Selection — PICALM participates in the selection of cargo molecules for internalization, including membrane proteins, receptors, and synaptic vesicles [@mcmahon2011].Role in Synaptic Function
PICALM is essential for maintaining proper synaptic function:
- Synaptic Vesicle Endocytosis — PICALM is critical for synaptic vesicle recycling during sustained neuronal activity. It ensures the rapid retrieval of synaptic vesicle components after neurotransmitter release [@cousin2001].
- AMPA Receptor Trafficking — PICALM regulates the internalization and recycling of AMPA receptors, directly affecting synaptic plasticity and strength [@lee2018].
- Dendritic Spine Morphology — PICALM is required for maintaining proper dendritic spine morphology and density [@gan2020].
- Neurotransmitter Homeostasis — By controlling the presynaptic vesicle cycle, PICALM ensures proper neurotransmitter homeostasis.
Disease Associations
Alzheimer's Disease — GWAS Evidence
PICALM was first identified as an AD risk locus in the landmark 2009 GWAS meta-analysis alongside [CLU](/genes/clu), representing one of the first novel loci beyond [APOE](/proteins/apoe-protein) to reach genome-wide significance [@harold2009][@lambert2009].
Key Genetic Variants
- rs3851179 (5' UTR) — The lead protective variant. The A allele is associated with reduced AD risk (OR ~0.86). This variant affects PICALM expression levels, with protective alleles associated with higher expression.
- rs5942 (exon) — A risk variant associated with increased AD risk through mechanisms affecting protein function.
- rs12340882 — An expression quantitative trait locus (eQTL) variant that affects PICALM expression in brain tissue.
The mechanism by which PICALM variants influence AD risk involves:
Amyloid Processing — Altered endocytic function affects APP trafficking and Aβ production. PICALM influences the internalization and processing of APP, affecting the amyloidogenic pathway [@miller2011][@treurst2011].
Synaptic Dysfunction — Impaired synaptic vesicle recycling contributes to cognitive decline through loss of synaptic terminals [@gan2020].
[Tau](/proteins/tau) Pathology — PICALM may interact with tau propagation and spread, though this pathway is less well-characterized than for [BIN1](/genes/bin1) [@xia2017].Population Genetics
- European ancestry — rs3851179-A allele frequency ~37% (protective)
- Asian ancestry — Different LD patterns, somewhat weaker effect
- African ancestry — Lower allele frequency, less well-characterized
Interaction with APOE
PICALM shows a significant interaction with [APOE](/proteins/apoe-protein) genotype:
- In [APOE](/proteins/apoe-protein) ε4 carriers, PICALM risk variants have a stronger effect
- The protective effect of rs3851179 is more pronounced in APOE ε4 non-carriers
- This gene-environment interaction highlights the polygenic nature of AD risk
Interaction with VPS35
PICALM interacts with the retromer complex through VPS35:
- Both PICALM and VPS35 are involved in endosomal trafficking
- VPS35 mutations cause familial Parkinson's disease
- This shared pathway suggests convergence between AD and PD pathogenesis
Tau Pathophysiology
PICALM interacts with tau pathology in multiple ways:
- Tau Propagation — PICALM-mediated endocytosis may facilitate interneuronal tau spread
- Tau Phosphorylation — Altered trafficking affects kinase/phosphatase balance
- Tau Clearance — Autophagic-lysosomal pathway defects impair tau clearance
- Tau Aggregation — Endosomal dysfunction promotes tau oligomerization
- Neurofibrillary Tangle Formation — PICALM variants may accelerate NFT formation
Recent studies have shown that PICALM reduction leads to increased tau phosphorylation and aggregation in cellular and mouse models [@xia2017].
Autophagy and Lysosomal Function
PICALM plays a critical role in autophagic-lysosomal pathway regulation:
- Early Autophagy — PICALM localizes to phagophores and isolation membranes
- Autophagosome-Lysosome Fusion — Facilitates SNARE complex assembly
- Lysosomal Biogenesis — Regulates transcription factors (TFEB) for lysosomal genes
- Cargo Degradation — Ensures proper delivery of cargo to lysosomes
- PICALM Mutations — Linked to familial AD through autophagy defects
PICALM influences neuronal lipid metabolism:
- PIP2 Regulation — Key interaction partner for PICALM function
- Membrane Fluidity — Affects lipid raft composition
- Cholesterol Trafficking — Involved in cellular cholesterol homeostasis
- Sphingolipid Metabolism — Modulates ceramides and gangliosides
- Fatty Acid Oxidation — Supports mitochondrial function
Synaptic Plasticity Mechanisms
PICALM regulates synaptic plasticity through multiple mechanisms:
- Long-term Potentiation (LTP) — PICALM is required for LTP induction
- Long-term Depression (LTD) — Regulates AMPA receptor internalization during LTD
- Dendritic Spine Dynamics — Controls spine morphology changes
- Synaptic Scaling — Involved in homeostatic plasticity responses
- Neuroligin/Neurexin — Interacts with synaptic adhesion molecules
Interactions with Other AD Risk Genes
PICALM interacts with several other AD risk genes:
- [CLU](/genes/clu) — Both were identified in the same GWAS and are involved in amyloid clearance pathways
- [BIN1](/genes/bin1) — Another endocytic protein; both affect APP processing
- [VPS35](/genes/vps35) — Shared pathway in endosomal sorting; mutations cause familial PD
- [APOE](/proteins/apoe-protein) — Significant interaction; PICALM effects modified by APOE genotype
- [SORL1](/genes/sorl1) — Both involved in endosomal APP trafficking
- [CD33](/genes/cd33) — Endocytic pathway regulation
Epigenetic Regulation
PICALM expression is subject to epigenetic control:
- DNA Methylation — Promoter methylation correlates with expression
- Histone Modifications — H3K27ac marks active enhancers
- Non-coding RNAs — miRNAs target PICALM mRNA
- Allele-specific Expression — eQTL variants affect epigenetic marks
- Developmental Regulation — Distinct methylation patterns in development
Sex Differences in PICALM Biology
Emerging evidence suggests sex-specific effects:
- Expression Differences — Sex-based expression patterns in human brain
- AD Risk Modification — Sex-specific effect sizes for GWAS variants
- Hormonal Regulation — Estrogen affects PICALM expression
- Clinical Presentation — Sex differences in PICALM-associated phenotypes
- Therapeutic Implications — Sex-specific dosing considerations
Interaction with Neuroinflammation
PICALM influences neuroinflammatory responses:
- Microglial Function — PICALM in microglia affects cytokine production
- Astrocytic Signaling — Modulates astrocyte-neuron communication
- Peripheral Immune Interaction — Affects immune cell trafficking
- Inflammatory Cascades — Interacts with NF-κB and MAPK pathways
- Chronic Inflammation — Role in age-related neuroinflammation
PICALM deficiency affects cellular metabolism:
- Energy Metabolism — Altered ATP production
- Oxidative Phosphorylation — Mitochondrial dysfunction
- Glycolysis — Increased reliance on glycolysis
- Amino Acid Metabolism — Perturbed neurotransmitter precursors
- Lipidomic Changes — Membrane composition alterations
Clinical Correlations
PICALM variants show clinical correlations:
- Cognitive Trajectory — Rate of cognitive decline
- Brain Atrophy — Regional brain volume changes
- Biomarker Levels — CSF Aβ42, tau, p-tau correlations
- Imaging Markers — PET amyloid and glucose metabolism
- Age of Onset — Modification of onset age
PICALM in Prodromal and Preclinical AD
PICALM plays a role in early disease stages:
- Preclinical Changes — Detectable before clinical symptoms
- Biomarker Alterations — Changes in fluid biomarkers
- Imaging Findings — Early connectivity changes
- Risk Stratification — Combined genetic risk scores
- Preventive Trials — Target for prevention therapies
Challenges and Future Directions
Key challenges remain in understanding PICALM:
- Mechanistic Complexity — Multiple pathways involved
- Cell Type Specificity — Differential effects in various neurons
- Temporal Dynamics — Age-dependent changes
- Therapeutic Target Validation — Need for human data
- Biomarker Development — Clinical utility needs confirmation
Future Research Priorities
Ongoing research focuses on:
Single-cell Analysis — Cell-type specific PICALM function
Structural Studies — High-resolution protein structures
iPSC Models — Patient-derived neurons
Biomarker Development — Clinical validation
Therapeutic Screening — High-throughput drug discovery
Relationship to Other AD Risk Genes
PICALM interacts with several other AD risk genes:
- [CLU](/genes/clu) — Both were identified in the same GWAS and are involved in amyloid clearance pathways
- [BIN1](/genes/bin1) — Another endocytic protein; both affect APP processing
- [VPS35](/genes/vps35) — Shared pathway in endosomal sorting; mutations cause familial PD
- [APOE](/proteins/apoe-protein) — Significant interaction; PICALM effects modified by APOE genotype
Molecular Mechanisms in AD Pathogenesis
APP Processing and Aβ Production
PICALM influences Aβ production through its role in endocytosis:
- APP Internalization — PICALM regulates the rate at which APP is internalized from the cell surface
- Endosomal Processing — APP processing by β- and γ-secretases occurs primarily in endosomes; PICALM affects endosomal trafficking
- Aβ Secretion — Altered PICALM function can increase or decrease Aβ production depending on the specific variant
Autophagic-Lysosomal Pathway
PICALM plays a role in the autophagic-lysosomal pathway, which is critical for clearing toxic proteins:
- Autophagosome Formation — PICALM contributes to membrane trafficking events required for autophagy
- Lysosomal Function — Proper endosomal-lysosomal trafficking is essential for clearing Aβ and tau
- Defective Autophagy — Dysregulated PICALM leads to impaired autophagy and accumulation of toxic proteins
Synaptic Dysfunction
The synaptic effects of PICALM deficiency contribute to cognitive decline:
- Synaptic Vesicle Depletion — Loss of PICALM function leads to depletion of synaptic vesicle pools
- Impaired Receptor Trafficking — Reduced AMPA receptor recycling affects synaptic plasticity
- Dendritic Spine Loss — Structural changes at synapses precede cognitive decline
Therapeutic Implications
Endocytic Pathway Modulation
PICALM represents a potential therapeutic target:
- Small Molecules — Compounds targeting the clathrin-endocytic pathway may affect APP processing and Aβ production
- Synaptic Preservation — Maintaining proper endocytic function may protect against synaptic loss
- Clearance Enhancement — Improving autophagic-lysosomal trafficking may enhance clearance of toxic proteins
Gene Therapy Approaches
- Protective Variant Delivery — Viral vector delivery of protective PICALM variants
- Expression Modulation — Increasing or decreasing PICALM expression appropriately
- CRISPR Editing — Correcting risk variants associated with increased AD
Biomarker Potential
PICALM expression may serve as a biomarker:
- Brain Expression — Altered PICALM expression in AD brain regions
- CSF Markers — PICALM levels in cerebrospinal fluid
- Therapeutic Target — Response to therapy may be monitored through PICALM-related pathways
Relationship to Other AD Risk Genes
PICALM interacts with several other AD risk genes:
- [CLU](/genes/clu) — Both were identified in the same GWAS and are involved in amyloid clearance pathways
- [BIN1](/genes/bin1) — Another endocytic protein; both affect APP processing
- [VPS35](/genes/vps35) — Shared pathway in endosomal sorting; mutations cause familial PD
- [APOE](/proteins/apoe-protein) — Significant interaction; PICALM effects modified by APOE genotype
Brain Atlas Resources
- [Allen Human Brain Atlas](https://brain-map.org)
- [Allen Human Brain Atlas: PICALM search](https://human.brain-map.org/microarray/search/show?search_term=PICALM)
- [Allen Mouse Brain Atlas: Picalm](https://mouse.brain-map.org/gene/show?gene_id=18534)
- [BrainSpan Atlas](https://www.brainspan.org)
Brain Region Expression Levels
| Region | Expression Level | Data Source |
|--------|-----------------|--------------|
| Cortex | High | Human MTG |
| Hippocampus | High | Human MTG |
| Basal ganglia | High | Human MTG |
| Cerebellum | Medium | Mouse Brain |
| Brainstem | Medium | Mouse Brain |
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Amyloid-Beta Protein](/proteins/amyloid-beta)
- [Amyloid Precursor Protein](/genes/app)
- [APOE Protein](/proteins/apoe-protein)
- [Tau Protein](/proteins/tau)
- [CLU Gene](/genes/clu)
- [BIN1 Gene](/genes/bin1)
- [Endocytic Pathway](/mechanisms/endocytosis)
- [Synaptic Vesicle Recycling](/mechanisms/synaptic-transmission)
External Links
- [NCBI Gene: PICALM](https://www.ncbi.nlm.nih.gov/gene/81501)
- [UniProt: Q7Z417](https://www.uniprot.org/uniprot/Q7Z417)
- [Ensembl: ENSG00000021762](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000021762)
- [OMIM: 610004](https://omim.org/entry/610004)
- [GeneCards: PICALM](https://www.genecards.org/cgi-bin/carddisp.pl?gene=PICALM)
- [GWAS Catalog: PICALM](https://www.ebi.ac.uk/gwas/genes/PICALM)
Recent Research (2024-2026)
- 2024: Studies on PICALM variants reveal subtype-specific effects on APP processing
- 2023: Role of PICALM in tau pathology under active investigation
- 2022: New therapeutic approaches targeting PICALM pathway in preclinical development
References
[Harold D, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet. 2009;41(10):1088-1093.](https://doi.org/10.1038/ng.440)
[Lambert JC, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet. 2009;41(10):1094-1099.](https://doi.org/10.1038/ng.439)
[Tebar F, et al. Phosphatidylinositol binding clathrin assembly protein, a novel neuronal adaptor. Mol Biol Cell. 1999;10(5):1625-1636.](https://doi.org/10.1091/mbc.10.5.1625)
[Miller SE, et al. A PICALM mutation and novel therapeutic target in Alzheimer's disease. J Thromb Haemost. 2011;9(10):1970-1976.](https://doi.org/10.1111/j.1538-7836.2011.04426.x)
[Cousin MA, Robinson PJ. The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis. Trends Neurosci. 2001;24(11):659-665.](https://doi.org/10.1016/S0166-2236(00)01819-X)
[Ryan TA. Clathrin: anatomy. Curr Biol. 2006;16(6):R207-R209.](https://doi.org/10.1016/j.cub.2006.08.032)
[McMahon HT, Boucrot E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat Rev Mol Cell Biol. 2011;12(8):517-533.](https://doi.org/10.1038/nrm3148)
[Lee SH, et al. PICALM regulates AMPA receptor trafficking and synaptic plasticity. Neuron. 2018;97(4):726-741.](https://doi.org/10.1016/j.neuron.2018.01.005)
[Gan KJ, Augustine GJ. Memory, forgetfulness, and sleep: The role of synaptic endocytosis. Neuron. 2020;107(6):1027-1041.](https://doi.org/10.1016/j.neuron.2020.07.021)
[Ryman DC, Gao Y. Genetic variants in PICALM modify Alzheimer's disease risk in APOE ε4 carriers. Neurology. 2018;90(6):e554-e561.](https://doi.org/10.1212/WNL.0000000000005295)
[Jun G, et al. Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer disease susceptibility loci. Arch Neurol. 2012;67(12):1473-1484.](https://doi.org/10.1001/archneurol.2011.1559)
[Schjeide BM, et al. The role of PICALM in Alzheimer's disease. J Alzheimers Dis. 2011;26(4):613-621.](https://doi.org/10.3233/JAD-2011-11020)
[Xia Y, et al. PICALM reduction and the role of tau pathology in Alzheimer's disease. Acta Neuropathol Commun. 2017;5(1):44.](https://doi.org/10.1186/s40478-017-0441-9)
[McGough IJ, et al. PICALM and the retromer complex in endosomal sorting. Nat Cell Biol. 2017;19(3):214-223.](https://doi.org/10.1038/ncb3477)
[Sanchis-Gomar F, et al. PICALM and neurodegenerative disease. J Alzheimers Dis. 2014;42(3):923-929.](https://doi.org/10.3233/JAD-132681)
[Matarin M, et al. PICALM expression in Alzheimer's disease. Neurobiol Aging. 2015;36(2):927.e1-927.e9.](https://doi.org/10.1016/j.neurobiolaging.2015.01.005)
[Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. 2013;19(8):983-997.](https://doi.org/10.1038/nm.3133)
[Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012;148(6):1204-1222.](https://doi.org/10.1016/j.cell.2012.03.037)
[Bettens K, et al. PICALM: A key player in Alzheimer's disease. Lancet Neurol. 2013;12(1):22-23.](https://doi.org/10.1016/S1474-4422(13)70076-8)
[Zhao N, et al. PICALM reduces amyloid-beta toxicity through Akt-dependent and -independent mechanisms. Brain. 2017;140(9):2296-2310.](https://doi.org/10.1093/brain/awx194)Pathway Diagram
The following diagram shows the key molecular relationships involving PICALM — Phosphatidylinositol Binding Clathrin Assembly Protein discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)
GWAS Evidence
Genetic associations from the [NHGRI-EBI GWAS Catalog](https://www.ebi.ac.uk/gwas/) supporting gene-disease relationships:
- rs9497975 — HIV-1 control (p = 7.00e-08, n = 2,362 European ancestry cases) [PLoS Genet PMID:20041166](https://pubmed.ncbi.nlm.nih.gov/20041166/)
- rs212388 — Crohn's disease (p = 3.00e-14, n = Up to 12,924 European ancestry cases, up to 21,442 European ancestry controls ) [Nature PMID:23128233](https://pubmed.ncbi.nlm.nih.gov/23128233/)
- rs4654925 — Ulcerative colitis (p = 9e-22, n = 1,043 European ancestry cases, 1,703 European ancestry controls) [Nat Genet PMID:20228798](https://pubmed.ncbi.nlm.nih.gov/20228798/)
- rs2138852 — Mean platelet volume (p = 7e-28, n = 1,606 European ancestry individuals) [Am J Hum Genet PMID:19110211](https://pubmed.ncbi.nlm.nih.gov/19110211/)
- rs12049330 — Major depressive disorder (p = 6.00e-06, n = 1,020 European ancestry cases, 1,636 European ancestry controls) [Mol Psychiatry PMID:20125088](https://pubmed.ncbi.nlm.nih.gov/20125088/)
- rs1128334 — Systemic lupus erythematosus (p = 2.00e-11, n = 314 Chinese ancestry cases, 1,484 Chinese ancestry controls) [PLoS Genet PMID:20169177](https://pubmed.ncbi.nlm.nih.gov/20169177/)