ANKRD11 — Ankyrin Repeat Domain 11

ANKRD11 — Ankyrin Repeat Domain 11

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ANKRD11 — Ankyrin Repeat Domain 11</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ANKRD11</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ANKRD11 — Ankyrin Repeat Domain 11</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=ANKRD11" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

ANKRD11 (Ankyrin Repeat Domain 11) encodes a transcriptional regulator containing ankyrin repeat domains. It acts as a cofactor for histone acetylation and is crucial for neuronal development and function. This gene is notable for causing KBG syndrome when mutated and for its broader roles in chromatin regulation and neurodevelopment.

Overview

ANKRD11 — Ankyrin Repeat Domain 11

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ANKRD11 — Ankyrin Repeat Domain 11</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>ANKRD11</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ANKRD11 — Ankyrin Repeat Domain 11</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Gene</td>
</tr>
<tr>
<td class="label">NCBI</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/?term=ANKRD11" target="_blank">Search NCBI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

ANKRD11 (Ankyrin Repeat Domain 11) encodes a transcriptional regulator containing ankyrin repeat domains. It acts as a cofactor for histone acetylation and is crucial for neuronal development and function. This gene is notable for causing KBG syndrome when mutated and for its broader roles in chromatin regulation and neurodevelopment.

Overview

ANKRD11 (Ankyrin Repeat Domain 11) encodes a transcriptional co-regulator that modulates gene expression through histone acetylation. It is highly expressed in the brain and has been implicated in neurodevelopment and neurodegeneration. Mutations cause KBG syndrome, characterized by intellectual disability, dysmorphic features, and macrocephaly. [@gallagher2015]

ANKRD11 is a member of the ankyrin repeat-containing family of transcriptional regulators. It functions as a histone acetyltransferase coactivator, interacting with p300/CBP to enhance transcription of genes involved in neuronal development, synaptic function, and cell growth. The gene is located on chromosome 16q24.3 and encodes a protein of 2,556 amino acids. [@sirmaci2011]

Gene and Protein Structure

Gene Organization

The ANKRD11 gene spans approximately 15 kb on chromosome 16q24.3 and contains 13 exons. It encodes multiple transcripts due to alternative splicing. The gene is conserved across mammals, with high expression in brain and other tissues.

Protein Domains

ANKRD11 contains several functional domains:

• Ankyrin repeats (N-terminal): 8 ankyrin repeat motifs that mediate protein-protein interactions
• Transcriptional activation domain (C-terminal): Contains motifs for interacting with histone acetyltransferases
• Nuclear localization signals: Promote nuclear import
• PEST sequences: Regulatory sequences affecting protein stability

Function

Transcriptional Regulation

ANKRD11 functions primarily as a transcriptional coactivator:

• Histone acetylation: ANKRD11 interacts with p300/CBP to enhance histone acetylation at target gene promoters
• Chromatin remodeling: Facilitates open chromatin configuration for transcription
• Gene-specific targeting: Regulates different gene sets in different cellular contexts
• Cell type-specific effects: Different functions in neurons vs. other cell types

Neurodevelopmental Functions

During brain development, ANKRD11 plays critical roles:

• Neuronal differentiation: Promotes differentiation of neural progenitor cells
• Synaptogenesis: Regulates formation of excitatory synapses
• Dendritic development: Influences dendritic arborization and spine formation
• Axon guidance: Contributes to proper axon pathfinding

Synaptic Function

In mature neurons, ANKRD11 continues to play important roles:

• Synaptic plasticity: Modulates activity-dependent synaptic changes
• Transcriptional regulation at synapses: Controls expression of synaptic proteins
• Homeostatic responses: Helps neurons adapt to changes in activity

Cell Growth and Differentiation

Beyond the nervous system, ANKRD11 affects:

• Cell cycle regulation: Modulates progression through the cell cycle
• Differentiation: Promotes differentiation in various cell types
• Metabolism: Influences cellular metabolic programs

Expression Pattern

ANKRD11 shows widespread but specific expression:

• Brain: High expression in cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and cerebellum
• Neurons: Present in excitatory and inhibitory neurons
• Development: High expression during brain development, maintained in adulthood
• Other tissues: Expression in heart, lung, kidney, and other organs
• Subcellular Localization: Nuclear, associated with chromatin

Disease Associations

KBG Syndrome

KBG syndrome is an autosomal dominant neurodevelopmental disorder caused by heterozygous ANKRD11 mutations:

Genetics:

• Inheritance: Usually de novo, occasionally inherited from affected parent
• Mutation types: Truncating mutations, missense mutations, deletions
• Prevalence: Estimated at 1 in 10,000-100,000 births

• Developmental delay/intellectual disability: Varies from mild to moderate
• Characteristic facial features: Broad nasal bridge, triangular face, thick eyebrows, anteverted nares
• Macrocephaly: Large head circumference
• Short stature: Height below average
• Dental anomalies: Delayed eruption, oligodontia
• Seizures: Occur in ~25% of cases
• Behavioral problems: Autism spectrum disorder, ADHD, anxiety
• Other features: Hearing loss, strabismus, cryptorchidism

Mechanism:

• Haploinsufficiency: Loss of one functional copy is sufficient to cause disease
• Dominant negative effects: Some mutations may interfere with the wild-type allele
• Altered transcription: Dysregulation of genes controlled by ANKRD11

Autism Spectrum Disorder

ANKRD11 is implicated in [autism spectrum disorder](/diseases/autism):

• Shared genetics: Many KBG syndrome patients meet autism criteria
• Independent mutations: ANKRD11 variants found in autism without KBG features
• Synaptic dysfunction: Altered synaptic gene expression

Intellectual Disability

ANKRD11 is one of the more common genetic causes of intellectual disability:

• Prevalence: Estimated at 0.5-1% of intellectual disability cases
• Non-syndromic cases: Some individuals have intellectual disability without other KBG features
• Mechanism: Disrupted transcriptional regulation during development

Epilepsy

Seizures are a common feature of ANKRD11-related disorders:

• Types: Generalized, focal, and absence seizures reported
• Onset: Variable, often in childhood
• Response: Generally responsive to standard antiepileptic drugs

Cancer

ANKRD11 has been implicated in cancer:

• Tumor suppressor role: ANKRD11 is considered a potential tumor suppressor
• Somatic mutations: Found in various cancers
• Mechanism: Altered transcriptional regulation affects cell growth

Therapeutic Implications

Current Approaches

Emerging Therapies

• Histone deacetylase inhibitors: May compensate for reduced histone acetylation
• Gene therapy: Viral vector delivery to restore ANKRD11 expression
• Small molecule upregulators: Increase expression of the wild-type allele
• Targeted neural circuits: Modulate specific pathways affected by ANKRD11 loss

Research Directions

• iPSC models: Patient-derived neurons for drug screening
• Animal models: Understanding mechanisms and testing therapies
• Biomarkers: Markers for disease progression and treatment response

Research Highlights

Key Findings

Model Systems

• Mouse models: Knockout and knock-in models recapitulate aspects of KBG syndrome
• iPSC neurons: Patient-derived cells for mechanistic studies
• Organoids: Brain organoids for developmental studies

See Also

• [Genes Directory](/genes/)
• [Intellectual Disability](/diseases/intellectual-disability)
• [Autism Spectrum Disorder](/diseases/autism)
• [Chromatin Remodeling](/mechanisms/chromatin-remodeling)
• [Transcriptional Regulation](/mechanisms/transcriptional-regulation)
• [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
• [KBG Syndrome](/diseases/kbg-syndrome)

External Links

• [NCBI Gene: ANKRD11](https://www.ncbi.nlm.nih.gov/gene/55470)
• [UniProt: ANKRD11](https://www.uniprot.org/uniprot/Q9Y2J0)
• [OMIM: ANKRD11](https://omim.org/entry/611160)
• [GeneReviews: KBG Syndrome](https://www.ncbi.nlm.nih.gov/books/NBKX4937/)
• [Ensembl: ANKRD11](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000167535)

Brain Atlas Resources

• [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data
• [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression

References