ANKLE2
Ankyrin Repeat and LEM Domain Containing 2
Gene Information Card
| Symbol | ANKLE2 |
|---|---|
| Full Name | Ankyrin Repeat and LEM Domain Containing 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.33 |
| NCBI Gene ID | 23141 ncbi.nlm.nih.gov/gene/23141 |
| Ensembl ID | ENSG00000111247 |
| UniProt ID | Q86XL3 |
| OMIM ID | 616062 |
| HGNC ID | 29001 |
| Aliases | LEM domain containing 3, LEMD3, ANKLE2 |
Description
ANKLE2 encodes a nuclear envelope protein containing ankyrin repeats and a LEM (LAP2-emerin-MAN1) domain. It localizes to the inner nuclear membrane and is involved in nuclear envelope assembly, chromatin organization, and cell cycle regulation. Mutations in ANKLE2 cause primary autosomal recessive microcephaly and may contribute to other neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary autosomal recessive microcephaly 16 (MCPH16) | Loss-of-function mutations disrupt nuclear envelope integrity and mitotic spindle orientation, impairing neural progenitor proliferation. | OMIM #616062; PMID: 27745832 |
| Microcephaly with or without pontocerebellar hypoplasia | Biallelic ANKLE2 variants lead to reduced brain size and cerebellar abnormalities. | ClinVar; PMID: 27745832 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Testis | 8.5 | Medium |
| Ovary | 6.1 | Low |
| Lung | 4.3 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.0 | High expression |
| HeLa | 9.5 | Medium expression |
| SH-SY5Y | 11.2 | High expression |
| U2OS | 8.0 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1576C>T (p.Arg526Ter) | Nonsense | Rare | Loss of function; truncated protein |
| c.1685G>A (p.Arg562Gln) | Missense | Rare | Impaired nuclear envelope localization |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of translation initiation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to premature stop codons or absent protein.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005635 | • GO:0005637 |
| • GO:0006997 | • GO:0051321 |
| • GO:0000776 |
Pathways
• REACT:170143
• REACT:170144
Protein Summary
ANKLE2 is a 913-amino acid protein with an N-terminal LEM domain and C-terminal ankyrin repeats. It anchors to the inner nuclear membrane and interacts with BAF (barrier-to-autointegration factor) to regulate chromatin tethering and nuclear envelope reassembly during mitosis. The protein is essential for proper brain development.
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