1. Gene Aliases

Ankyrin Repeat Domain 23, DARP, MARP3, Ankyrin Repeat Domain-Containing Protein 23, Diabetes Related Ankyrin Repeat Protein, Muscle Ankyrin Repeat Protein 3, FLJ32449, Diabetes-Related Ankyrin Repeat Protein

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=ANKRD23&keywords=Ankrd23]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

2q11.2 copy number variation syndrome: The 2q11.2 copy number variation syndrome can result in the loss of up to 27 protein-coding genes. Patients with 2q11.2 deletions were reported to have developmental delay, speech delay and ADHD, while subjects with 2q11.2 duplications apart from developmental delay had gastroesophageal reflux and short stature (DOI: 10.1002/ajmg.a.37269). [https://www.wikipathways.org/pathways/WP5221.html].

Cardiomyocyte signaling pathways converging on Titin: Involvement of Titin in cardiomyocyte signaling pathways and its effect on Protein Quality Control pathways as well as Hypertrophic Signalling within a cardiomyocyte. [https://www.wikipathways.org/pathways/WP5344.html].

GO terms:

fatty acid metabolic process [The chemical reactions and pathways involving fatty acids, aliphatic monocarboxylic acids liberated from naturally occurring fats and oils by hydrolysis. GO:0006631]

positive regulation of transcription by RNA polymerase II [Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. GO:0045944]

regulation of sarcomere organization [Any process that modulates the rate, frequency or extent of myofibril assembly by organization of muscle actomyosin into sarcomeres. The sarcomere is the repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs. GO:0060297]

response to mechanical stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a mechanical stimulus. GO:0009612]

response to muscle stretch [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a myofibril being extended beyond its slack length. GO:0035994]

MSigDB Signatures:

WP_CARDIOMYOCYTE_SIGNALING_PATHWAYS_CONVERGING_ON_TITIN: Cardiomyocyte signaling pathways converging on Titin [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CARDIOMYOCYTE_SIGNALING_PATHWAYS_CONVERGING_ON_TITIN.html]

7. Gene Descriptions

NCBI Gene Summary: This gene is a member of the muscle ankyrin repeat protein (MARP) family and encodes a protein with four tandem ankyrin-like repeats. The protein is localized to the nucleus, functioning as a transcriptional regulator. Expression of this protein is induced during recovery following starvation. [provided by RefSeq, Jul 2008]

GeneCards Summary: ANKRD23 (Ankyrin Repeat Domain 23) is a Protein Coding gene. Diseases associated with ANKRD23 include Glioblastoma Proneural Subtype and Total Anomalous Pulmonary Venous Return 1. Among its related pathways are 2q11.2 copy number variation syndrome and Cardiomyocyte signaling pathways converging on Titin. Gene Ontology (GO) annotations related to this gene include titin binding.

UniProtKB/Swiss-Prot Summary: May be involved in the energy metabolism. Could be a molecular link between myofibrillar stretch-induced signaling pathways and muscle gene expression.

8. Cellular Location of Gene Product

Cytoplasmic expression in myocytes and smooth muscle cells. Mainly localized to the nucleoplasm & cytosol. In addition localized to the actin filaments. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000163126/subcellular]

9. Mechanistic Information

Summary

ANKRD23 encodes a protein that is part of the muscle ankyrin repeat proteins (MARP) family, specifically involved in muscle gene expression and energy metabolism [CS: 7]. It binds to the N2A region of titin, a giant sarcomeric protein, affecting its phosphorylation by PKA and is itself phosphorylated by PKA and PKC, which could alter its structure or function [CS: 6].

In heart-related diseases and toxicities, the expression of ANKRD23 is often dysregulated [CS: 7]. For instance, in cardiac hypertrophy, where the heart muscle enlarges due to increased workload or injury, ANKRD23 (DARP) is upregulated [CS: 7]. This upregulation likely serves to manage the increased mechanical stress on the heart muscle by modulating the structure and function of sarcomeric proteins like titin, thus maintaining the integrity and function of cardiac muscle cells [CS: 6]. Additionally, in conditions like type 2 diabetes, which can lead to altered energy metabolism in cardiac tissues, the expression of ANKRD23 is affected [CS: 6]. Its role in energy metabolism, particularly under diabetic conditions, suggests its involvement in adapting the heart muscle to altered energy states, possibly by influencing pathways like AMPK activity that are critical in cellular energy homeostasis [CS: 6]. This upregulation in response to stress or altered energy states seems to be a cellular mechanism to counteract the initial stressors, ensuring continued function and survival of cardiac cells under adverse conditions [CS: 7].

10. Upstream Regulators

No relevant information pertaining to this subject matter was identified in the existing body of literature.

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: skeletal muscle, tongue (group enriched) [https://www.proteinatlas.org/ENSG00000163126/tissue]

Cell type enchanced: skeletal myocytes (cell type enriched) [https://www.proteinatlas.org/ENSG00000163126/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

No DisGenNet altered expression associations were found for Ankrd23 and diseases associated with Heart