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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FAM222A
family with sequence similarity 222 member A
Chromosome 12 · 12q24.11
NCBI Gene: 84915Ensembl: ENSG00000139438.7HGNC: HGNC:25915UniProt: Q5U5X8
11PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Swiss-Prot Reviewed
angina pectorismyocardial infarctiongoutsmoking initiation
✦AI Summary

FAM222A encodes Aggregatin, a 47-kDa protein predominantly expressed in the central nervous system that plays a pathogenic role in Alzheimer's disease (AD) 1. The primary function of Aggregatin involves facilitating amyloid-beta (Aβ) aggregation through direct physical interaction via its N-terminal Aβ binding domain 12. Mechanistically, Aggregatin accumulates within amyloid plaques and stabilizes Aβ peptide assembly, with molecular dynamics simulations confirming stable protein-peptide complexes 3. In disease pathology, FAM222A was identified as a brain atrophy susceptibility gene through imaging genetics analysis 1. Elevated Aggregatin expression occurs in AD patient brains and mouse models, with reactive astrocytes identified as primary cellular sources 4. Functionally, intracerebroventricular infusion or forced expression exacerbates neuroinflammation and cognitive dysfunction in AD models, whereas FAM222A ablation suppresses amyloid deposit formation, neuroinflammation, and cognitive deficits 1. Clinically, FAM222A co-expression correlates with multiple AD-related pathway genes across brain tissues 5, suggesting coordinated involvement in disease pathogenesis. Virtual screening identified potential therapeutic candidates (Cefpiramide, Diniprofylline, Fostriecin, Droperidol) targeting Aggregatin 6, indicating therapeutic potential in AD intervention strategies.

Sources cited
1
FAM222A encodes Aggregatin protein; protein accumulates in amyloid plaques, interacts with Aβ via N-terminal domain, facilitates Aβ aggregation, and ablation suppresses amyloid deposits and cognitive deficits in AD models
PMID: 31964863
2
Aggregatin interacts with Aβ peptide (1-42) through its N-terminal Aβ binding domain and facilitates Aβ aggregation
PMID: 33533447
3
Molecular dynamics simulations confirm stable complexes between Aggregatin and Aβ peptides (1-42 and 1-28)
PMID: 41408807
4
Aggregatin is expressed predominantly in CNS with elevated levels in AD brains; reactive astrocytes are primary cellular sources of Aggregatin expression
PMID: 33139980
5
FAM222A expression correlates with 673 co-expressed genes genome-wide, with 298 from CNS tissues enriched in multiple AD-related pathways
PMID: 37092222
6
Virtual screening identified Cefpiramide, Diniprofylline, Fostriecin, and Droperidol as potential therapeutic candidates targeting Aggregatin
PMID: 37552909
Disease Associationsⓘ20
angina pectorisOpen Targets
0.42Moderate
myocardial infarctionOpen Targets
0.41Moderate
goutOpen Targets
0.34Weak
smoking initiationOpen Targets
0.32Weak
Abruptio PlacentaeOpen Targets
0.27Weak
Abnormal brain morphologyOpen Targets
0.27Weak
asthmaOpen Targets
0.23Weak
acute tonsillitisOpen Targets
0.21Weak
mathematical abilityOpen Targets
0.21Weak
Abnormality of the skeletal systemOpen Targets
0.12Weak
Alzheimer diseaseOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.07Suggestive
type 2 diabetes mellitusOpen Targets
0.07Suggestive
corneal ulcerOpen Targets
0.05Suggestive
amyotrophic lateral sclerosisOpen Targets
0.04Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.04Suggestive
intestinal hypomagnesemia 1Open Targets
0.04Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.04Suggestive
Familial isolated hypoparathyroidismOpen Targets
0.03Suggestive
familial isolated hypoparathyroidism due to agenesis of parathyroid glandOpen Targets
0.03Suggestive
Pathogenic Variants1
NM_032829.3(FAM222A):c.284A>T (p.His95Leu)Likely pathogenic
Abnormal brain morphology
★☆☆☆→ Residue 95
View on ClinVar ↗
Related Genes
MAB21L1Protein interaction78%MEIS1Protein interaction78%MEIS2Protein interaction78%PBX1Protein interaction78%PBX3Protein interaction78%
Tissue Expression6 tissues
Ovary
100%
Brain
92%
Liver
31%
Heart
23%
Bone Marrow
22%
Lung
11%
Gene Interaction Network
Click a node to explore
FAM222AMAB21L1MEIS1MEIS2PBX1PBX3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q5U5X8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.75LoF Tolerant
pLIⓘ
0.37Tolerant
Observed/Expected LoF0.40 [0.23–0.75]
RankingsWhere FAM222A stands among ~20K protein-coding genes
  • #16,750of 20,598
    Most Researched11
  • #5,470of 5,498
    Most Pathogenic Variants1
  • #5,940of 17,882
    Most Constrained (LOEUF)0.75
Genes detectedFAM222A
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Ab initio and comparative 3D modeling of FAM222A-encoded protein and target-driven-based virtual screening for the identification of novel therapeutics against Alzheimer's disease.
PMID: 37552909
J Mol Graph Model · 2023
1.00
2
FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease.
PMID: 31964863
Nat Commun · 2020
0.90
3
Gene Co-Expression Analysis of Multiple Brain Tissues Reveals Correlation of FAM222A Expression with Multiple Alzheimer's Disease-Related Genes.
PMID: 37092222
J Alzheimers Dis · 2024
0.80
4
Assessment of the Interaction of Aggregatin Protein with Amyloid-Beta (Aβ) at the Molecular Level via In Silico Analysis.
PMID: 33533447
Acta Chim Slov · 2020
0.70
5
Reactive astrocytes express Aggregatin (
PMID: 33139980
Intractable Rare Dis Res · 2020
0.60