ANXA11 — Annexin A11

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ANXA11 — Annexin A11

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ANXA11 — Annexin A11

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ANXA11 — Annexin A11</th>
</tr>
<tr> [@liu2022]
<td class="label">Symbol</td> [@teyssou2021]
<td><strong>ANXA11</strong></td> [@balasa2025]
</tr> [@smith2017]
<tr> [@ncbi]
<td class="label">Full Name</td> [@omim]
<td>Annexin A11</td> [@httpswwwncbinlmnihgovgene]
</tr> [@httpsensemblorghomosapiensgenesummarygensg]
<tr> [@httpsomimorgentry]
<td class="label">Chromosome</td> [@httpswwwuniprotorguniprotp]
<td>10q22.3</td> [@anxa]
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/311" target="_blank">311</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000122359" target="_blank">ENSG00000122359</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/602572" target="_blank">602572</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P50995" target="_blank">P50995</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[ALS](/diseases/als), [FTD](/diseases/ftd), [ALS-FTD](/diseases/als)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Motor neurons, Cortex, Hippocampus, Spinal cord</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Mutations</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">p.D40G (LCD; ALS-FTD)<br>p.G38R (founder variant)<br>p.R235Q

...

ANXA11 — Annexin A11

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ANXA11 — Annexin A11</th>
</tr>
<tr> [@liu2022]
<td class="label">Symbol</td> [@teyssou2021]
<td><strong>ANXA11</strong></td> [@balasa2025]
</tr> [@smith2017]
<tr> [@ncbi]
<td class="label">Full Name</td> [@omim]
<td>Annexin A11</td> [@httpswwwncbinlmnihgovgene]
</tr> [@httpsensemblorghomosapiensgenesummarygensg]
<tr> [@httpsomimorgentry]
<td class="label">Chromosome</td> [@httpswwwuniprotorguniprotp]
<td>10q22.3</td> [@anxa]
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/311" target="_blank">311</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000122359" target="_blank">ENSG00000122359</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/602572" target="_blank">602572</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/P50995" target="_blank">P50995</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[ALS](/diseases/als), [FTD](/diseases/ftd), [ALS-FTD](/diseases/als)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Motor neurons, Cortex, Hippocampus, Spinal cord</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Mutations</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">p.D40G (LCD; ALS-FTD)<br>p.G38R (founder variant)<br>p.R235Q (calcium domain)<br>p.R346C (annexin repeat)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/igg4-related-cholangitis" style="color:#ef9a9a">IgG4-related cholangitis</a>, <a href="/wiki/neurodegenerative-diseases" style="color:#ef9a9a">NEURODEGENERATIVE DISEASES</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">amyotrophic lateral sclerosis</a>, <a href="/wiki/bladder-cancer" style="color:#ef9a9a">bladder cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">18 edges</a></td>
</tr>
</table>

ANXA11 — Annexin A11

Introduction

Anxa11 (Annexin A11) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

ANXA11 (Annexin A11) is a gene located on chromosome 10q22.3 that encodes annexin A11, a calcium-dependent phospholipid-binding protein belonging to the annexin superfamily.
ANXA11 was identified as a novel [als](/diseases/als) gene in 2017, and subsequent studies have established it as an important genetic contributor to the ALS-[ftd](/diseases/ftd) spectrum
[@anxa2019][@anxa2022].
Mutations in ANXA11 account for approximately 1–2% of familial ALS cases and a smaller fraction of sporadic ALS [@anxa2019].

The annexin A11 protein is unique among annexins due to its long N-terminal low-complexity domain (LCD), which mediates interactions with RNA granules and [stress-granules](/mechanisms/stress-granules).
ALS-linked mutations disrupt calcium homeostasis, stress granule dynamics, and nuclear envelope integrity, connecting ANXA11 to the converging pathogenic pathways of [rna-metabolism](/mechanisms/rna-metabolism) dysfunction and [protein-aggregation](/mechanisms/protein-aggregation)
in Motor [neurons](/entities/neurons) Disease [@anxa2020][@annexin2025].

The gene is catalogued as NCBI Gene ID [^311] and OMIM [^602572].

Function

Normal Protein Function

Annexin A11 is a 505-amino-acid protein with two distinct functional domains:

N-terminal low-complexity domain (LCD, residues 1–188): An intrinsically disordered region enriched in glycine and proline residues.

This domain mediates [liquid-liquid-phase-separation](/mechanisms/liquid-liquid-phase-separation) (LLPS) and interactions with RNA granules, [stress-granules](/mechanisms/stress-granules), and P-bodies.
It also contains a calcyclin-binding domain [@anxa2019][@anxa2020].

C-terminal annexin core (residues 189–505): Contains four conserved annexin repeats that bind calcium ions and phospholipids, enabling membrane association. The annexin core mediates calcium-dependent binding to cellular membranes, lysosomes, and the nuclear envelope [@annexin2025].

Cellular Roles

RNA granule transport: ANXA11 acts as a molecular tether between RNA granules and lysosomes, enabling long-distance mRNA transport along axons — a process critical for [motor-neurons](/cell-types/motor-neurons) function and local protein synthesis at synapses [@anxa2020][@annexin2025].
Stress granule dynamics: The LCD mediates incorporation into stress granules under cellular stress, and ANXA11 participates in the disassembly of stress granules during stress recovery [@anxa2020].
Nuclear envelope integrity: ANXA11 localizes to the nuclear envelope and contributes to nuclear lamina stability. Loss of function disrupts nuclear morphology and may contribute to [nucleocytoplasmic-transport-defects](/mechanisms/nucleocytoplasmic-transport-defects) [@annexin2025].
Calcium signaling: Through its annexin repeats, ANXA11 participates in calcium-dependent signaling cascades and membrane dynamics [@anxa2020].
Cell division: ANXA11 plays a role in cytokinesis and midbody formation during cell division.

Brain Expression

[motor-neurons](/cell-types/motor-neurons)
Cerebral [cortex](/brain-regions/cortex)
[hippocampus](/brain-regions/hippocampus)
[spinal-cord](/brain-regions/spinal-cord)
[cerebellum](/brain-regions/cerebellum)

Expression data is available from the [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=ANXA11).

Disease Associations

ANXA11 mutations are linked to the following neurodegenerative conditions:

[als](/diseases/als) — both familial and sporadic forms
[ftd](/diseases/ftd) — particularly the ALS-FTD spectrum
[semantic-dementia](/diseases/semantic-dementia) — rare cases with p.D40G variant [@anxa2022]

Key Mutations

Mutations cluster primarily in two regions: the N-terminal LCD and the calcium-binding annexin repeats [@anxa2019][@anxa2022]:

Low-Complexity Domain Mutations:

p.D40G: The most frequently reported ALS-associated variant.

Located in the LCD, it disrupts stress granule dynamics, impairs RNA granule-lysosome tethering, and causes calcium dysregulation.
Associated with ALS-FTD phenotype and, rarely, semantic variant PPA [@anxa2022].

p.G38R: A founder variant identified in multiple ALS families. Alters LCD phase separation properties [@anxa2019].
p.G189E: At the LCD-annexin core boundary; affects domain-domain interactions.

Annexin Core Mutations:

p.R235Q: Located in the first annexin repeat; disrupts calcium-dependent membrane binding and stress granule disassembly [@anxa2020].
p.R346C: In the third annexin repeat; impairs calcium sensing.

Clinical Correlations:
Patients with variants in the low-complexity domain presented unique clinical features, including late-onset disease (mean ~60 years), a high prevalence of ALS-FTD overlap, faster initial progression, and a tendency for
bulbar-onset disease [@anxa2022].
In a Chinese ALS cohort of 1,587 patients, ANXA11 variants were found in 29 patients (1.8%), with 20 distinct non-synonymous variants
identified [@anxa2019][@anxa2020].

Pathogenic Mechanisms

Stress Granule Dysregulation

ALS-linked ANXA11 mutations impair the normal dynamics of stress granules — cytoplasmic RNA-protein condensates that form in response to cellular stress.
Wild-type ANXA11 promotes stress granule disassembly during stress recovery; mutant forms fail to properly dissolve stress granules, leading to their persistence and potential conversion into pathological aggregates
[@anxa2020].
This connects ANXA11 to the broader paradigm of [rna-metabolism](/mechanisms/rna-metabolism) dysfunction in ALS, alongside [tdp-43](/proteins/tdp-43), [fus-protein](/proteins/fus-protein), and other RNA-binding proteins.

Calcium Homeostasis Disruption

Annexin repeat mutations directly impair calcium-dependent membrane binding. LCD mutations also cause secondary calcium dysregulation by altering the protein's interaction with membranes and organelles. Disturbed calcium homeostasis activates downstream cascades including [excitotoxicity](/entities/excitotoxicity), mitochondrial stress, and apoptotic signaling [@anxa2020].

Nuclear Envelope Dysfunction

Studies in Drosophila models and human tissues demonstrate that ANXA11 mutations cause nuclear envelope defects, including abnormal nuclear morphology, disrupted nuclear lamina organization, and impaired nucleocytoplasmic transport [@annexin2025]. This mechanism parallels nuclear pore complex dysfunction observed with [c9orf72](/proteins/c9orf72-protein) repeat expansions and connects to [nucleocytoplasmic-transport-defects](/mechanisms/nucleocytoplasmic-transport-defects) as a convergent ALS mechanism.

Impaired Axonal RNA Transport

ANXA11's role as a molecular tether between RNA granules and lysosomes is critical for mRNA delivery along the long axons of [motor-neurons](/cell-types/motor-neurons).
ALS mutations disrupt this tethering function, potentially starving distal axonal compartments of essential mRNAs for local protein
synthesis — contributing to the dying-back axonopathy characteristic of ALS [@anxa2020][@annexin2025].

Brain Atlas Resources

[Allen Brain Atlas](https://brain-map.org)
[Allen Human Brain Atlas: ANXA11 search](https://human.brain-map.org/microarray/search/show?search_term=ANXA11)
[Allen Mouse Brain Atlas: ANXA11 search](https://mouse.brain-map.org/search/index.html?query=ANXA11)
[Allen Cell Type Atlas](https://portal.brain-map.org/atlases-and-data/rnaseq)
[BrainSpan Developmental Transcriptome](https://www.brainspan.org)
[Genes Index](/genes/genes)
[Proteins Index

External Links

PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[Allen Brain Atlas](https://www.brain-map.org/)

Background

The study of Anxa11 (Annexin A11) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Unknown, ANXA11 mutations prevail in Chinese ALS patients with and without cognitive dementia (2019)](https://doi.org/10.1212/NXG.0000000000000237)

[Unknown, ANXA11 mutations in ALS cause dysregulation of calcium homeostasis and stress granule dynamics (2020)](https://doi.org/10.1126/scitranslmed.aax3993)

[Unknown, ANXA11 mutations are associated with amyotrophic lateral sclerosis-Frontotemporal Dementia (2022)](https://doi.org/10.1002/acn3.51645)

[Unknown, Annexin A11 mutations are associated with nuclear envelope dysfunction in vivo and in human tissues (2025)](https://doi.org/10.1093/brain/awae275)

[Liu X, et al., Genetic analysis of and clinical characteristics associated with ANXA11 variants in a Chinese cohort with amyotrophic lateral sclerosis. Neurobiology of Disease, 2022. . DOI (2022)](https://doi.org/10.1016/j.nbd.2022.105903)

[Teyssou E, et al., Genetic screening of ANXA11 revealed novel mutations linked to amyotrophic lateral sclerosis. Neurobiology of Aging, 2021. . DOI (2021)](https://doi.org/10.1016/j.neurobiolaging.2020.10.015)

[Balasa M, et al., Semantic variant primary progressive aphasia with ANXA11 p.D40G. Brain Communications, 2025. . DOI (2025)](https://doi.org/10.1093/braincomms/fcaf076)

[Smith BN, et al., Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis. Science Translational Medicine, 2017. . DOI (2017)](https://doi.org/10.1126/scitranslmed.aad9157)

Unknown, NCBI Gene: ANXA11 (n.d.)

Unknown, OMIM: [602572](/genes) | [Proteins Index## External Links (n.d.)

- NCBI Gene:, https://www.ncbi.nlm.nih.gov/gene/311 (n.d.)

- Ensembl:, https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000122359 (n.d.)

- OMIM:, https://omim.org/entry/602572 (n.d.)

- UniProt:, https://www.uniprot.org/uniprot/P50995 (n.d.)

- Allen Human Brain Atlas:, ANXA11 expression (n.d.)

Pathway Diagram

The following diagram shows the key molecular relationships involving anxa11 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving ANXA11 — Annexin A11 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

ANXA11

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-anxa11
kg_node_id	ANXA11
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-307f3514abfd
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-anxa11'}
_schema_version	1

📊 Evidence Profile Foundational

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50%

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10

Outgoing

21

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

ANXA11 — Annexin A11

ANXA11 — Annexin A11

ANXA11 — Annexin A11

ANXA11 — Annexin A11

Introduction

Overview

Function

Normal Protein Function

Cellular Roles

Brain Expression

Disease Associations

Key Mutations

Pathogenic Mechanisms

Stress Granule Dysregulation

Calcium Homeostasis Disruption

Nuclear Envelope Dysfunction

Impaired Axonal RNA Transport

Brain Atlas Resources

External Links

Background

References

Pathway Diagram

Pathway Diagram

💬 Discussion