TMEM43 (LUMA) – Function, Localization, and Biological Role OpenAI o3-deep-research-2025-06-26 127 citations 2025-12-27T22:12:41.428880

TMEM43 (LUMA) – Function, Localization, and Biological Role

Overview and Key Characteristics

Transmembrane protein 43 (TMEM43), also known as LUMA, is a highly conserved 45 kDa protein that localizes to multiple cellular membranes. It was initially identified as an integral membrane component of the nuclear envelope (specifically the inner nuclear membrane, INM) (pmc.ncbi.nlm.nih.gov). Recent studies revealed TMEM43 is also present at certain cell–cell junctions, including the adherens junctions of epithelial cells and the composite junctions of cardiac intercalated discs (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In cardiomyocytes, TMEM43 has been observed predominantly at the intercalated disc and sarcolemma (the plasma membrane of muscle cells) rather than the nucleus (pmc.ncbi.nlm.nih.gov). Consistently, TMEM43 is described as a “widespread plaque protein” found in the INM, endoplasmic reticulum (ER), and zonula adherens junctions across many tissues (pmc.ncbi.nlm.nih.gov). TMEM43’s dual presence in the nuclear envelope and at cell junctions suggests it plays a role in maintaining structural connectivity from the cell periphery to the nucleus.

TMEM43 contains multiple hydrophobic segments and is predicted to span the membrane four times (a tetraspan membrane protein) (pubmed.ncbi.nlm.nih.gov). Both the N- and C-termini face the cytoplasmic side (or nucleoplasmic side at the INM) according to topology predictions, positioning TMEM43 to interact with cytoskeletal and nuclear components inside the cell. TMEM43 is expressed widely in human tissues, with highest mRNA levels reported in placenta, and significant levels in heart, skin, ovary and other organs (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This broad expression pattern, combined with its high sequence conservation from yeast to humans (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), underscores a fundamental cellular function.

Subcellular Localization and Structural Interactions

Inner Nuclear Membrane: At the nuclear periphery, TMEM43 resides in the inner nuclear membrane where it interacts with key components of the nuclear lamina. It has been shown to bind lamin A/C, lamin B1, SUN2, and emerin – all important proteins of the nuclear envelope (pmc.ncbi.nlm.nih.gov). Through these interactions, TMEM43 helps anchor the nuclear lamina to the membrane. In particular, TMEM43 plays a critical role in the correct localization of emerin at the INM (pmc.ncbi.nlm.nih.gov). Emerin is a nuclear membrane protein that connects the lamina to the cytoskeleton and contributes to gene regulation; normally, emerin’s retention at the INM depends on binding lamin A/C (pmc.ncbi.nlm.nih.gov). TMEM43 appears to stabilize emerin in the nuclear envelope, as loss of TMEM43 causes emerin to mislocalize (pmc.ncbi.nlm.nih.gov). Consistent with this, Bengtsson & Otto (2008) found that TMEM43 (LUMA) directly interacts with emerin and influences emerin’s distribution in the nucleus (pmc.ncbi.nlm.nih.gov). By helping attach the lamina (via lamin–emerin connections) to the inner membrane, TMEM43 contributes to nuclear structural integrity and shape. Indeed, partial loss of Tmem43 in mouse hearts triggers a DNA damage response (DDR) and premature cellular senescence, suggesting compromised nuclear integrity when TMEM43 is insufficient (pmc.ncbi.nlm.nih.gov).

Cell–Cell Junctions: Outside the nucleus, TMEM43 is found in the plaques of cell junctions that experience mechanical stress. Franke et al. (2014) discovered that TMEM43 is a constitutive component of the cytoplasmic plaques at zonula adherens junctions in various epithelia and at the composite junctions in cardiac intercalated discs (pubmed.ncbi.nlm.nih.gov). In these locations, TMEM43 co-localizes with other junctional proteins (such as cadherins, catenins, desmosomal proteins) and was notably absent from the nuclear envelope in those cells (pubmed.ncbi.nlm.nih.gov). This finding overturned earlier assumptions that TMEM43 was only a nuclear protein, and firmly placed it as a structural component of cellular adhesion sites. In cardiomyocytes, intercalated discs contain three types of junctions – fascia adherens (anchoring actin filaments via N-cadherin and catenins), desmosomes (linking intermediate filaments via desmoplakin, plakoglobin, etc.), and gap junctions (for ionic coupling via connexins) (pmc.ncbi.nlm.nih.gov). TMEM43 (LUMA) localizes to the adherens and desmosomal regions of the intercalated disc (pubmed.ncbi.nlm.nih.gov), making it one of the proteins that connect the contractile apparatus of one cell to another. In line with this, Christensen et al. (2011) examined human cardiac tissue and found TMEM43 mainly at the sarcolemmal membrane, including intercellular junctions, with little or no signal at nuclei (pmc.ncbi.nlm.nih.gov). Thus, TMEM43 is present at multiple membrane systems: the nuclear envelope (INM and associated ER membrane) and the plasma membrane at sites of cell adhesion. This strategic localization positions TMEM43 as a linker between the nucleoskeleton and cytoskeleton, and between cells in a tissue (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Biological Function and Mechanosignaling Role

TMEM43’s primary function is structural and organizational – it contributes to the architecture of the nucleus and to intercellular connections, thereby maintaining tissue integrity. Because it spans membranes and binds structural proteins, TMEM43 is thought to facilitate mechanotransduction, the conversion of mechanical stimuli into biochemical signals (pmc.ncbi.nlm.nih.gov). Specifically, TMEM43 is implicated in the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, which physically couples the nuclear interior to the cytoskeleton (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By bridging lamins and SUN2 at the inner nuclear membrane (components of LINC) (pmc.ncbi.nlm.nih.gov), TMEM43 helps transmit forces from the cytoskeleton to the nucleus. These forces can influence chromatin organization and gene expression programs in response to mechanical cues (pmc.ncbi.nlm.nih.gov). For example, mechanical strain on a cell can be conveyed through TMEM43-associated complexes to alter gene expression as part of the cell’s adaptation to stress (pmc.ncbi.nlm.nih.gov). In muscle cells, which endure repeated contraction-relaxation cycles, this mechanosensitive pathway is critical for adjusting gene expression to mechanical load (pmc.ncbi.nlm.nih.gov).

Consistent with a role in force transmission, TMEM43 interacts not only with nuclear lamina components but also with actin filaments. In immunoprecipitation experiments, TMEM43 was found in complex with β-actin, suggesting it anchors or associates with the actin cytoskeleton (pmc.ncbi.nlm.nih.gov). Notably, when the disease-causing mutant form TMEM43-S358L is expressed in mice, it shows reduced binding to emerin and actin, and a portion of the mutant protein mislocalizes to the cytoplasm (pmc.ncbi.nlm.nih.gov). The loss of these interactions coincides with activation of GSK-3β signaling in mutant hearts (pmc.ncbi.nlm.nih.gov). GSK-3β is a kinase involved in multiple pathways (including Wnt signaling), so its activation may reflect downstream consequences of a weakened nucleo-cytoskeletal linkage. These findings highlight that normal TMEM43 helps tether the cytoskeleton to the nuclear membrane, and that disrupting TMEM43 can perturb signaling pathways and cell structure.

At the intercalated disc, TMEM43 likely contributes to the strength and organization of cardiac cell–cell junctions. The intercalated disc is an essential structure for mechanical and electrical coupling between cardiomyocytes. By associating with adherens junction components (e.g. N-cadherin/catenin complex) and possibly desmosomal proteins, TMEM43 may stabilize the junctional plaque. Franke et al. observed that TMEM43 colocalizes with plakoglobin (JUP) and other junction markers at the intercalated disc (pubmed.ncbi.nlm.nih.gov), implying that TMEM43 is part of the protein network that links cadherin adhesion complexes to the cytoskeleton. This network ensures that contractile force is transmitted from one cell to the next and prevents cells from pulling apart during contraction. Loss of TMEM43 could therefore weaken cell–cell adhesion or alter the composition of junctional complexes. Indeed, there is evidence that TMEM43 influences the distribution of plakoglobin: in hearts of TMEM43 S358L mutant mice, plakoglobin was found aberrantly translocated into nuclei (away from the disc) (pmc.ncbi.nlm.nih.gov). This is significant because plakoglobin (γ-catenin) normally helps anchor desmosomes; its movement to the nucleus is associated with a suppression of Wnt/β-catenin signaling, a phenomenon seen in arrhythmogenic cardiomyopathies (pmc.ncbi.nlm.nih.gov). Thus, TMEM43’s integrity at the intercalated disc appears necessary to keep plakoglobin at the membrane and maintain proper Wnt signaling balance in cardiomyocytes.

In addition to structural roles, TMEM43 has been linked to ion channel regulation in certain cell types. Inner-ear studies indicate TMEM43 is important in cochlear supporting cells, which are glia-like cells connected by gap junctions. TMEM43 was found to physically interact with the gap-junction proteins Connexin26 and Connexin30 in these supporting cells (pmc.ncbi.nlm.nih.gov). By doing so, TMEM43 helps maintain the gap-junction mediated ionic coupling that is crucial for recycling potassium ions in the inner ear. A 2021 study demonstrated that a TMEM43 truncation mutant (p.Arg372Ter) disrupts passive K^+ currents in cochlear glial cells by impairing connexin function (pmc.ncbi.nlm.nih.gov). These glial gap junctions normally clear extracellular K^+ to sustain hair cell excitability; without functional TMEM43, the coupling is lost and hearing is compromised (pmc.ncbi.nlm.nih.gov). Separately, TMEM43 was also reported to interact with a two-pore K^+ channel (KCNK3) in the cochlea, suggesting a broader role in supporting the ion channels of these cells (pmc.ncbi.nlm.nih.gov). In summary, TMEM43 contributes to cellular communication – mechanical and electrical – by organizing membrane complexes (adherence junctions, gap junctions, and nuclear-cytoskeletal tethers).

Involvement in Signaling Pathways

While TMEM43 does not have known enzymatic activity, its position in cellular architecture allows it to influence several signaling pathways indirectly. One major pathway affected is the Wnt/β-catenin signaling pathway. Through its interaction with emerin and β-catenin-associated complexes, TMEM43 can modulate Wnt signaling outcomes in muscle cells (pmc.ncbi.nlm.nih.gov). Emerin, which TMEM43 helps localize, is known to bind and sequester β-catenin at the nuclear periphery, thereby repressing Wnt-driven gene transcription in cardiac and skeletal muscle (pmc.ncbi.nlm.nih.gov). If TMEM43 is lost or mutated, emerin’s function is altered, and β-catenin signaling can become dysregulated. In line with this, TMEM43 S358L mutant hearts showed reduced β-catenin levels and nuclear accumulation of plakoglobin (which can replace β-catenin in some transcriptional complexes) (pmc.ncbi.nlm.nih.gov). This suggests a shift toward Wnt signal suppression in the heart. Conversely, in the small intestine of the same TMEM43 mutant mice, researchers observed elevated β-catenin and cell proliferation (Ki-67), indicating heightened Wnt activity in gut epithelium (pmc.ncbi.nlm.nih.gov). Distinct tissues may thus respond differently to TMEM43 dysfunction, but it is clear TMEM43 is a node in the network that governs Wnt/β-catenin signaling and cell proliferation.

Another pathway tied to TMEM43 is the PPARγ pathway, which is involved in adipogenesis and metabolism. Interestingly, the promoter of the TMEM43 gene contains a response element for PPARγ (a lipid-activated transcription factor) (www.ncbi.nlm.nih.gov). TMEM43 has been identified as a potential target gene of PPARγ, linking it to fat metabolism and storage processes (pmc.ncbi.nlm.nih.gov). In support of this, a comprehensive study of hearts from ARVC patients showed that TMEM43 expression is associated with fibro-fatty changes: TMEM43 was upregulated in conjunction with adipogenic genes in diseased myocardium (pmc.ncbi.nlm.nih.gov). In a mouse model, the S358L mutation in TMEM43 led to diminished PPARγ activity in the heart (despite the heart accumulating fat) but paradoxically caused increased lipid absorption and PPARγ-related signaling in the intestine (pmc.ncbi.nlm.nih.gov). These findings hint that TMEM43 might normally help balance metabolic signaling between tissues, and that its mutation perturbs PPARγ-regulated pathways. Moreover, oxidative stress signals like oxidized LDL can activate PPARγ and have been linked to worse outcomes in ARVC patients with TMEM43 mutations (more fat infiltration and arrhythmias) (pmc.ncbi.nlm.nih.gov). This suggests TMEM43 is part of a pathophysiological loop where metabolic factors exacerbate cardiac dysfunction.

Inflammatory signaling pathways, such as NF-κB, are also influenced by TMEM43. Cell studies have shown that TMEM43 over-expression can activate the NF-κB pathway through EGFR (epidermal growth factor receptor) signaling (pmc.ncbi.nlm.nih.gov). In cancer cell models, TMEM43 was found to stabilize the pre-mRNA processing factor 3 (PRPF3), leading to enhanced NF-κB activity and promoting tumor cell survival and migration (pmc.ncbi.nlm.nih.gov). These data imply that TMEM43 can crosstalk with growth factor and transcriptional stress pathways, potentially by affecting how signals are transmitted to the nucleus. On the other hand, in certain contexts TMEM43 may protect cells: for instance, high TMEM43 expression in cardiomyocytes was reported to guard against sepsis-induced cardiac injury by inhibiting ferroptosis (an iron-dependent cell death) through an NF-κB-related mechanism (pmc.ncbi.nlm.nih.gov). Additionally, transcriptomic studies in human placenta have linked TMEM43 upregulation to inflammatory pathways and cognitive impairment in preterm infants, suggesting TMEM43-mediated NF-κB activation might have developmental effects (pmc.ncbi.nlm.nih.gov). Altogether, TMEM43 emerges as a component that interfaces with mechanical, metabolic, and inflammatory signaling, largely by virtue of its role in anchoring multi-protein complexes that regulate gene expression in response to stress or stimuli.

Clinical Significance and Disease Associations

Arrhythmogenic Cardiomyopathy (ARVC5)

The most prominent disease tied to TMEM43 is Arrhythmogenic Right Ventricular Cardiomyopathy type 5 (ARVC5), an inherited heart muscle disorder. A missense mutation in TMEM43, p.S358L, was identified as the cause of ARVC5 in a large Newfoundland kindred (pmc.ncbi.nlm.nih.gov). ARVC5 is a fully penetrant, lethal arrhythmic disorder, meaning virtually all mutation carriers develop disease and many suffer life-threatening arrhythmias (pmc.ncbi.nlm.nih.gov). Clinically, TMEM43-related ARVC often presents with ventricular arrhythmias in young adulthood and progresses to ventricular dysfunction with fibro-fatty replacement of myocardium (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In the original family studies, male carriers of TMEM43-S358L had a particularly poor prognosis – approximately 48% of affected men died suddenly by middle age, whereas women carriers showed later onset and longer survival (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This sex-influenced severity is a notable feature of ARVC5. Mechanistically, the S358L mutation in TMEM43 has multiple effects on cardiac cells: it causes mislocalization of TMEM43 protein, disrupts intercalated disc integrity, and triggers pro-fibrotic and pro-apoptotic signaling cascades (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Mutant hearts show hallmark ARVC changes – myocardial cell loss with fibrous and fatty infiltrates, especially in the right ventricle’s “triangle of dysplasia” region (pmc.ncbi.nlm.nih.gov).

At the molecular level, TMEM43-S358L leads to a cascade of signal transduction changes that drive disease. Studies in knock-in mice carrying the human S358L mutation revealed activation of TGF-β and NF-κB signaling, known promoters of fibrosis and inflammation, in mutant hearts (pmc.ncbi.nlm.nih.gov). There is also a disruption of Wnt/β-catenin signaling: as mentioned, plakoglobin relocates to the nucleus in mutant cardiomyocytes, effectively dampening β-catenin’s transcriptional activity and promoting an adipogenic gene program (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In line with this, genes involved in adipogenesis (like PPARγ targets) become upregulated, and a switch toward fat metabolism is observed in the heart (pmc.ncbi.nlm.nih.gov). TMEM43 has been identified as one of the genes upregulated by PPARγ in cardiac tissue, suggesting that the mutant protein (or its downstream effects) might feed into a feed-forward loop of fat accumulation in myocardium (pmc.ncbi.nlm.nih.gov). Additionally, the mutant S358L protein itself appears unstable; studies noted its overall expression level is reduced in heterozygous carriers, possibly due to protein misfolding and degradation (pmc.ncbi.nlm.nih.gov). This reduction may phenocopy a partial loss-of-function, where cells lack sufficient TMEM43 at both the nuclear envelope and cell junctions. Indeed, cardiomyocytes harboring S358L show ultrastructural abnormalities: electron microscopy documented disarray of desmosomes and gap junctions, and nuclei that were abnormally shaped or stiff (pmc.ncbi.nlm.nih.gov). Cell mechanical testing indicated the S358L mutation increases nuclear stiffness, consistent with a perturbation in nucleo-cytoskeletal connections (pmc.ncbi.nlm.nih.gov). All these changes – weakened cell adhesion, altered signaling, and mechanical stress – synergize to cause cardiomyocyte death and fibrofatty replacement, manifesting as ARVC.

From a clinical perspective, the discovery of TMEM43 mutations in ARVC has practical implications. Genetic testing now includes TMEM43 in panels for arrhythmogenic cardiomyopathy, allowing at-risk family members to be identified early (pmc.ncbi.nlm.nih.gov). Because male sex and intense exercise exacerbate ARVC5, carriers (especially men) are advised to limit vigorous physical activity to reduce arrhythmia risk (pmc.ncbi.nlm.nih.gov). Some centers have even suggested implantable defibrillators at a relatively young age for S358L carriers, given the high incidence of sudden death (pmc.ncbi.nlm.nih.gov). There is ongoing research into therapies that might target the pathways activated by TMEM43 mutations – for example, NF-κB or TGF-β inhibitors to curb fibrosis, or Wnt modulators to correct the adipogenic switch (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). While no mutation-specific therapy exists yet, the mechanistic insights gained from TMEM43 studies (such as its influence on PPARγ and Wnt signaling) are guiding new approaches to ARVC treatment.

Variants in TMEM43 have also been implicated in Emery–Dreifuss muscular dystrophy (EDMD)-like disease. EDMD is typically caused by mutations in emerin (EMD gene) or lamin A/C (LMNA), leading to muscle wasting, early joint contractures, and cardiac conduction defects. However, Liang et al. (2011) reported TMEM43 mutations (e.g. p.E85K and p.I91V) in patients with EDMD-type muscular dystrophy (pmc.ncbi.nlm.nih.gov). These individuals had progressive skeletal muscle weakness and contractures similar to EDMD, despite having normal emerin and lamin sequences (pmc.ncbi.nlm.nih.gov). The TMEM43 mutations in EDMD patients likely disrupt the same nuclear envelope network that emerin and lamins normally support. Muscle biopsies from TMEM43-mutant patients showed irregularly shaped nuclei, but immunostaining indicated emerin and other nuclear membrane proteins were still present (pmc.ncbi.nlm.nih.gov). This suggests TMEM43 mutations may cause a functional loss of emerin/lamin organization rather than complete absence. Indeed, researchers proposed that TMEM43 dysfunction leads to emerin mislocalization or degradation over time, weakening the LINC complex and nuclear-cytoskeletal connections in muscle (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The result is nuclear architectural defects and impaired mechanotransduction in muscle fibers, which can trigger muscle fiber damage and dystrophy. In support of this mechanism, experimental knockdown of TMEM43 in muscle cells causes loss of emerin from the nuclear membrane and abnormal nuclear morphology, recapitulating features of EDMD (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Thus, TMEM43 joins emerin and lamin A/C as a critical component of the nuclear envelope whose disruption can lead to EDMD. Clinically, TMEM43-linked EDMD is rare; it has been designated “EDMD7” in the literature to distinguish it from the X-linked (emerin) and autosomal (lamin A/C) forms (www.ncbi.nlm.nih.gov). Patients with TMEM43 mutations may have milder cardiac involvement than typical EDMD – for example, normal early echocardiograms with possible arrhythmias later in life (pmc.ncbi.nlm.nih.gov). However, they still benefit from monitoring for cardiomyopathy and from interventions like pacemakers if conduction block develops, similar to classic EDMD management.

Auditory Neuropathy and Hearing Loss

Another emerging role for TMEM43 is in the auditory system. Autosomal dominant auditory neuropathy spectrum disorder (ANSD) has been linked to a nonsense variant in TMEM43 (p.Arg372Ter) in two unrelated families (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Patients with this condition experience progressive hearing loss characterized by inability to understand speech despite the inner ear’s hair cells remaining functional (a disconnect between ear and auditory nerve) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Genetic analysis mapped the disorder to chromosome 3p25 and pinpointed the TMEM43 variant as causative (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Functional studies in mice carrying the Arg372Ter mutation provided insight into how TMEM43 supports hearing: the mutation led to degeneration of cochlear supporting cells and disruption of their gap junction coupling (pmc.ncbi.nlm.nih.gov). Normally, cochlear glial-like supporting cells are coupled by connexin gap junctions (Cx26 and Cx30) that allow dispersal of K^+ ions and metabolites. TMEM43 was found to interact with Cx26 and Cx30, and the mutant TMEM43 could not support the gap junction function, resulting in impaired ionic currents in the supporting cell network (pmc.ncbi.nlm.nih.gov). Essentially, loss of TMEM43 uncouples the supporting cells, hindering the inner ear’s ability to recycle ions after sound stimulation, which in turn compromises the firing of the auditory nerve. Importantly, this discovery had a real-world application: because the sensory hair cells were intact despite the neural dysfunction, patients were treated with cochlear implants, which bypass the defective neural coupling. After implantation, individuals with the TMEM43 mutation showed restored speech discrimination ability (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) – a striking example of precision medicine guided by the molecular understanding of TMEM43’s role. Beyond gap junctions, as noted earlier, TMEM43 in the cochlea may also interact with ion channels like KCNK3 (TASK-1), indicating it might broadly influence the ion homeostasis in the inner ear’s supporting cell microenvironment (pmc.ncbi.nlm.nih.gov). TMEM43’s involvement in ANSD highlights its importance in cell–cell communication, extending its functional repertoire from muscle and heart into the nervous system.

Other Associations (Cancer and Beyond)

Studies have hinted at connections between TMEM43 and cancer, though this area is still being explored. Some analyses have found that certain TMEM43 mutations or expression patterns correlate with cancer outcomes. For instance, TMEM43 gene variations were noted to have a negative association with tumor progression and cell survival in some cancers (pmc.ncbi.nlm.nih.gov). This suggests that loss-of-function TMEM43 mutations might impede cancer cell growth (potentially because the cells lose structural integrity or NF-κB signaling support). Paradoxically, other experiments indicate that high TMEM43 expression can promote oncogenic behaviors, as described earlier with NF-κB activation and PRPF3 stabilization driving cancer cell proliferation (pmc.ncbi.nlm.nih.gov). One hypothesis to reconcile this is that TMEM43’s impact on cancer may be tissue-specific or context-dependent: in some cells, TMEM43-mediated mechanotransduction is required for tumor invasion (for example, cancer cells might exploit nuclear-cytoskeletal connections to migrate and endure physical stresses), whereas in other contexts, TMEM43-triggered pathways like NF-κB might induce senescence or immune responses that actually limit tumor growth. Large-scale data are needed to clarify TMEM43’s role in malignancy.

Outside of disease, TMEM43 has become of interest in cell biology as a protein that links multiple systems. Some experts have called TMEM43/LUMA a “unifying finding for cell biology and cardiology,” since it connects fundamental cellular structures (junctions and nuclei) with the pathology of heart disease (pubmed.ncbi.nlm.nih.gov). Its discovery at intercalated discs has prompted a re-thinking of how nuclear proteins might also function at the cell surface to maintain tissue integrity (pubmed.ncbi.nlm.nih.gov). In the heart, TMEM43 sits at the intersection of mechanical and electrical syncytia – reinforcing desmosomes while also influencing gene expression – a combination crucial for preventing arrhythmia. As such, TMEM43 exemplifies the concept of the “nexus” protein that integrates structural scaffolds with signaling pathways. Ongoing research is investigating TMEM43 in other conditions, such as its potential role in cardiometabolic disorders (given the link to PPARγ and lipid handling) (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). There is also interest in whether TMEM43 variants contribute to idiopathic cardiac fibrosis or heart failure in the general population, beyond the rare ARVC5 mutation carriers (pubmed.ncbi.nlm.nih.gov).

Summary

TMEM43 (LUMA) is a membrane protein that plays a pivotal role in maintaining cell structure and communication. Anchored in both the nuclear envelope and in cell–cell junctions, TMEM43 provides a physical and functional link between the nucleus and the plasma membrane. It helps stabilize the nuclear architecture by tethering lamins and emerin at the inner membrane (pmc.ncbi.nlm.nih.gov), and it fortifies intercellular junctions in tissues subject to mechanical stress (pubmed.ncbi.nlm.nih.gov). Through these roles, TMEM43 is a key mediator of mechanotransduction, ensuring that mechanical forces are relayed to the nucleus to influence gene activity (pmc.ncbi.nlm.nih.gov). Its influence extends to various signaling pathways – notably Wnt/β-catenin, PPARγ, and NF-κB – which become dysregulated when TMEM43 is mutated (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The critical importance of TMEM43 is highlighted by the severe diseases associated with its mutations: a lethal arrhythmogenic cardiomyopathy (ARVC5) characterized by sudden cardiac death and fatty heart degeneration (pmc.ncbi.nlm.nih.gov), a form of muscular dystrophy (EDMD) that undermines nuclear stability in muscle cells (pmc.ncbi.nlm.nih.gov), and an auditory neuropathy that uncouples inner-ear support cells leading to hearing loss (pmc.ncbi.nlm.nih.gov). In each case, the pathology can be traced back to the loss of TMEM43’s structural support and the resultant cascade of abnormal signaling and cell stress.

Experts continue to investigate TMEM43 to fully map its interactome and regulation. As a protein with “broad cellular functions”, spanning muscle, heart, ear, and possibly cancer contexts (pubmed.ncbi.nlm.nih.gov), TMEM43 represents a nexus between cell architecture and function. Understanding TMEM43’s role offers valuable insight into how cells convert physical cues into biological responses, and provides avenues for therapeutic intervention – from gene therapy for inherited cardiomyopathy to targeted cochlear implants for hearing loss. As of 2024, TMEM43 stands as a prime example of how a single membrane protein can influence diverse physiological processes through its integrative structural role, and research into its mechanism remains an active and fruitful field.

References:

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  6. Liang, W.C. et al. (2011). TMEM43 mutations in Emery-Dreifuss muscular dystrophy-related myopathy. Ann. Neurol. 69(6): 1005–1013. DOI: 10.1002/ana.22338 (pmc.ncbi.nlm.nih.gov).

  7. Zhao, Y. et al. (2021). A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder. Proc. Natl. Acad. Sci. U.S.A. 118(22): e2019681118. DOI: 10.1073/pnas.2019681118 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

  8. Orgil, B.-O. et al. (2023). The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model. Am. J. Physiol. Heart Circ. Physiol. 324(6): H866–H880. DOI: 10.1152/ajpheart.00712.2022 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

  9. Orgil, B.-O. et al. (2025). Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases. Int. J. Mol. Sci. 26(14): 6856. DOI: 10.3390/ijms26146856 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

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Citations

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  4. AnnotationURLCitation(end_index=1330, start_index=1196, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=More%20recent%20reports%20have%20demonstrated,DSP')
  5. AnnotationURLCitation(end_index=1662, start_index=1495, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=The%20transmembrane%20protein%2043%20,observed%20in%20female%20mutation%20carriers')
  6. AnnotationURLCitation(end_index=2092, start_index=1965, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=In%20a%20series%20of%20recent,In%20CJs%2C%20LUMA')
  7. AnnotationURLCitation(end_index=2611, start_index=2459, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=45%20kDa%2C%20expressed%20in%20the,Genetic%20mutations%20and%20gene')
  8. AnnotationURLCitation(end_index=2767, start_index=2612, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=ER%20membranes%20in%20many%20cell,Expression%20of%20TMEM43%20is%20also')
  9. AnnotationURLCitation(end_index=3019, start_index=2866, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=Transmembrane%20protein%2043%20,that%20are%20permeable%20to%20sodium')
  10. AnnotationURLCitation(end_index=3180, start_index=3020, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=TMEM43%20is%20an%20integral%20membrane,Expression%20of%20TMEM43%20is%20also')
  11. AnnotationURLCitation(end_index=3729, start_index=3568, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=location%20and%20organization,interactions%20to%20the%20intercalated%20disks')
  12. AnnotationURLCitation(end_index=4073, start_index=3912, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=location%20and%20organization,interactions%20to%20the%20intercalated%20disks')
  13. AnnotationURLCitation(end_index=4423, start_index=4262, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=location%20and%20organization,interactions%20to%20the%20intercalated%20disks')
  14. AnnotationURLCitation(end_index=4693, start_index=4532, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=location%20and%20organization,interactions%20to%20the%20intercalated%20disks')
  15. AnnotationURLCitation(end_index=4955, start_index=4853, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=,Google%20Scholar')
  16. AnnotationURLCitation(end_index=5452, start_index=5294, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=progression%20of%20various%20cancers%20in,to%20play%20a%20critical%20role')
  17. AnnotationURLCitation(end_index=5968, start_index=5807, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=we%20have%20discovered%20that%2C%20in,to%20reconsiderations%20of%20the%20molecular')
  18. AnnotationURLCitation(end_index=6319, start_index=6158, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=we%20have%20discovered%20that%2C%20in,to%20reconsiderations%20of%20the%20molecular')
  19. AnnotationURLCitation(end_index=6925, start_index=6763, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=of%20muscle%20cells,%E2%80%9Cdomino%20effect%E2%80%9D%20disruption%20of%20the')
  20. AnnotationURLCitation(end_index=7180, start_index=7019, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=we%20have%20discovered%20that%2C%20in,to%20reconsiderations%20of%20the%20molecular')
  21. AnnotationURLCitation(end_index=7615, start_index=7481, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=More%20recent%20reports%20have%20demonstrated,DSP')
  22. AnnotationURLCitation(end_index=8058, start_index=7916, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=Transmembrane%20protein%2043%20,S358L%20mutation%20causes')
  23. AnnotationURLCitation(end_index=8232, start_index=8059, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=Schema%20of%20the%20nuclear%20envelope,membrane%3B%20ONM%2C%20outer%20nuclear%20membrane')
  24. AnnotationURLCitation(end_index=8787, start_index=8650, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=cellular%20processes%20,is%20thought%20to%20play%20a')
  25. AnnotationURLCitation(end_index=9109, start_index=8955, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=cytoskeleton%20are%20essential%20for%20a,is%20thought%20to%20play%20a')
  26. AnnotationURLCitation(end_index=9283, start_index=9110, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=Schema%20of%20the%20nuclear%20envelope,membrane%3B%20ONM%2C%20outer%20nuclear%20membrane')
  27. AnnotationURLCitation(end_index=9481, start_index=9364, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=location%20and%20organization,33')
  28. AnnotationURLCitation(end_index=9839, start_index=9660, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=role%20in%20mechanosensation%20by%20transmitting,Emerins%20are%20ubiquitously%20expressed%20in')
  29. AnnotationURLCitation(end_index=10139, start_index=10002, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=cellular%20processes%20,is%20thought%20to%20play%20a')
  30. AnnotationURLCitation(end_index=10481, start_index=10302, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=role%20in%20mechanosensation%20by%20transmitting,Emerins%20are%20ubiquitously%20expressed%20in')
  31. AnnotationURLCitation(end_index=10946, start_index=10765, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L680%20interacted%20with,calcineurin%20splice%20variant%2C%20A%CE%B21%2C%20resulted')
  32. AnnotationURLCitation(end_index=11326, start_index=11145, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L680%20interacted%20with,calcineurin%20splice%20variant%2C%20A%CE%B21%2C%20resulted')
  33. AnnotationURLCitation(end_index=11607, start_index=11426, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L680%20interacted%20with,calcineurin%20splice%20variant%2C%20A%CE%B21%2C%20resulted')
  34. AnnotationURLCitation(end_index=12644, start_index=12483, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=we%20have%20discovered%20that%2C%20in,to%20reconsiderations%20of%20the%20molecular')
  35. AnnotationURLCitation(end_index=13411, start_index=13216, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=analysis%20found%20significantly%20differentially%20expressed,and%20PPARG%20signaling%20thereby%20contributing')
  36. AnnotationURLCitation(end_index=13830, start_index=13641, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=diminished%20PPARG%20activities%20and%20significantly,suggest%20that%20cardiometabolic%20assessment%20in')
  37. AnnotationURLCitation(end_index=14504, start_index=14369, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=p,subjects%2C%20and%20speech%20discrimination%20was')
  38. AnnotationURLCitation(end_index=14937, start_index=14802, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=p,subjects%2C%20and%20speech%20discrimination%20was')
  39. AnnotationURLCitation(end_index=15243, start_index=15108, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=p,subjects%2C%20and%20speech%20discrimination%20was')
  40. AnnotationURLCitation(end_index=15562, start_index=15418, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=2014%3B357%3A159%E2%80%93172.%20doi%3A%2010.1007%2Fs00441,M')
  41. AnnotationURLCitation(end_index=16291, start_index=16159, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=critical%20role%20in%20emerin%20localization,47')
  42. AnnotationURLCitation(end_index=16611, start_index=16477, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=tissues%20and%20predominately%20localized%20to,47')
  43. AnnotationURLCitation(end_index=17107, start_index=16912, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=analysis%20found%20significantly%20differentially%20expressed,and%20PPARG%20signaling%20thereby%20contributing')
  44. AnnotationURLCitation(end_index=17560, start_index=17371, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=diminished%20PPARG%20activities%20and%20significantly,suggest%20that%20cardiometabolic%20assessment%20in')
  45. AnnotationURLCitation(end_index=18094, start_index=17974, title='TMEM43 transmembrane protein 43 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/79188#:~:text=This%20gene%20belongs%20to%20the,provided%20by')
  46. AnnotationURLCitation(end_index=18357, start_index=18215, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=preferential%20loss%20of%20compact%20myocardium,146%2C126')
  47. AnnotationURLCitation(end_index=18734, start_index=18583, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=preferential%20loss%20of%20compact%20myocardium,127%5D%2C%20sodium')
  48. AnnotationURLCitation(end_index=19164, start_index=18967, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=analysis%20found%20significantly%20differentially%20expressed,suggest%20that%20cardiometabolic%20assessment%20in')
  49. AnnotationURLCitation(end_index=19658, start_index=19518, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=mutation%20,higher%20fat%20displacement%20of%20myocytes')
  50. AnnotationURLCitation(end_index=20127, start_index=20003, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L78%20TMEM43%20was,12%2C14')
  51. AnnotationURLCitation(end_index=20435, start_index=20311, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L78%20TMEM43%20was,12%2C14')
  52. AnnotationURLCitation(end_index=20981, start_index=20881, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=senescence,MRNA')
  53. AnnotationURLCitation(end_index=21378, start_index=21221, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=The%20ELGAN%20cohort%20study%20of,study%20defined%20a%20potential%20link')
  54. AnnotationURLCitation(end_index=22091, start_index=21989, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=,Google%20Scholar')
  55. AnnotationURLCitation(end_index=22415, start_index=22254, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=The%20transmembrane%20protein%2043%20,Serial%20echocardiography%2C%20surface')
  56. AnnotationURLCitation(end_index=22763, start_index=22601, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=SCD%20develop%20fibrosis%20with%20fatty,survival%20with%20the%20median%20life')
  57. AnnotationURLCitation(end_index=22923, start_index=22764, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=pathogenic%20variants%20,carried%20on%20all%20recombinant%20arrhythmogenic')
  58. AnnotationURLCitation(end_index=23282, start_index=23152, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=,lethal%20arrhythmic%20disorder%20caused%20by')
  59. AnnotationURLCitation(end_index=23445, start_index=23283, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=SCD%20develop%20fibrosis%20with%20fatty,survival%20with%20the%20median%20life')
  60. AnnotationURLCitation(end_index=23885, start_index=23742, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=displayed%20intolerance%20to%20acute%20stress,We%20defined')
  61. AnnotationURLCitation(end_index=24021, start_index=23886, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L472%20and%20fibrosis,109%2C110%2C111')
  62. AnnotationURLCitation(end_index=24349, start_index=24190, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=stability%2C%20and%20mechanical%20function%20of,fatty%20replacement%20with')
  63. AnnotationURLCitation(end_index=24776, start_index=24641, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L472%20and%20fibrosis,109%2C110%2C111')
  64. AnnotationURLCitation(end_index=25205, start_index=25010, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=analysis%20found%20significantly%20differentially%20expressed,and%20PPARG%20signaling%20thereby%20contributing')
  65. AnnotationURLCitation(end_index=25353, start_index=25206, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=and%20fibrosis%20through%20various%20signaling,109%2C110%2C111')
  66. AnnotationURLCitation(end_index=25661, start_index=25510, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=preferential%20loss%20of%20compact%20myocardium,127%5D%2C%20sodium')
  67. AnnotationURLCitation(end_index=26038, start_index=25887, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=preferential%20loss%20of%20compact%20myocardium,127%5D%2C%20sodium')
  68. AnnotationURLCitation(end_index=26430, start_index=26235, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=analysis%20found%20significantly%20differentially%20expressed,and%20PPARG%20signaling%20thereby%20contributing')
  69. AnnotationURLCitation(end_index=26939, start_index=26773, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=arrhythmogenic%20right%20ventricular%20cardiomyopathy,0004.2011.01623.x.%20%5BDOI')
  70. AnnotationURLCitation(end_index=27206, start_index=27093, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=,2015%3B36%3A872%E2%80%93881')
  71. AnnotationURLCitation(end_index=27727, start_index=27625, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=,Google%20Scholar')
  72. AnnotationURLCitation(end_index=28046, start_index=27885, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=The%20transmembrane%20protein%2043%20,Serial%20echocardiography%2C%20surface')
  73. AnnotationURLCitation(end_index=28325, start_index=28195, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=,lethal%20arrhythmic%20disorder%20caused%20by')
  74. AnnotationURLCitation(end_index=28686, start_index=28551, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L472%20and%20fibrosis,109%2C110%2C111')
  75. AnnotationURLCitation(end_index=28820, start_index=28687, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=mutation%20,ACM%20patients%20with%20high%20serum')
  76. AnnotationURLCitation(end_index=29635, start_index=29495, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=localization%2C%20resulting%20in%20impaired%20cell,This')
  77. AnnotationURLCitation(end_index=29877, start_index=29779, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=,230%20Google')
  78. AnnotationURLCitation(end_index=30336, start_index=30176, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L894%20dystroglycan%2C%20beta,It%20was%20proposed%20that%20the')
  79. AnnotationURLCitation(end_index=30831, start_index=30647, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=in%20TMEM43%20resulting%20in%20emerin,dystrophy%2C%20joint%20contractures%2C%20and%20cardiomyopathy')
  80. AnnotationURLCitation(end_index=30995, start_index=30832, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=LINC%20complex%20interactions%20with%20nuclear,related%20myopathy%20phenotypes')
  81. AnnotationURLCitation(end_index=31525, start_index=31341, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=in%20TMEM43%20resulting%20in%20emerin,dystrophy%2C%20joint%20contractures%2C%20and%20cardiomyopathy')
  82. AnnotationURLCitation(end_index=31677, start_index=31526, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L905%20LINC%20complex,related%20myopathy%20phenotypes')
  83. AnnotationURLCitation(end_index=32136, start_index=31972, title='TMEM43 transmembrane protein 43 [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/79188#:~:text=Also%20known%20as%20LUMA%3B%20ARVC5%3B,is%20characterized%20by%20ventricular%20tachycardia')
  84. AnnotationURLCitation(end_index=32467, start_index=32307, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L894%20dystroglycan%2C%20beta,It%20was%20proposed%20that%20the')
  85. AnnotationURLCitation(end_index=33075, start_index=32897, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=Auditory%20neuropathy%20spectrum%20disorder%20,passive%20conductance%20current%20in%20cochlear')
  86. AnnotationURLCitation(end_index=33255, start_index=33076, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=Genes%20that%20are%20primarily%20expressed,Mechanistically%2C%20TMEM43%20interacts%20with%20the')
  87. AnnotationURLCitation(end_index=33568, start_index=33472, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=Significance')
  88. AnnotationURLCitation(end_index=33661, start_index=33569, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=Abstract')
  89. AnnotationURLCitation(end_index=33912, start_index=33766, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=discrimination,and%20their%20speech%20discrimination%20ability')
  90. AnnotationURLCitation(end_index=34092, start_index=33913, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=Genes%20that%20are%20primarily%20expressed,Mechanistically%2C%20TMEM43%20interacts%20with%20the')
  91. AnnotationURLCitation(end_index=34447, start_index=34312, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=p,subjects%2C%20and%20speech%20discrimination%20was')
  92. AnnotationURLCitation(end_index=34923, start_index=34788, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=p,subjects%2C%20and%20speech%20discrimination%20was')
  93. AnnotationURLCitation(end_index=35586, start_index=35450, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=p,speech%20discrimination%20ability%20was%20restored')
  94. AnnotationURLCitation(end_index=35730, start_index=35587, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=connexin,speech%20discrimination%20ability%20was%20restored')
  95. AnnotationURLCitation(end_index=36203, start_index=36059, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=2014%3B357%3A159%E2%80%93172.%20doi%3A%2010.1007%2Fs00441,M')
  96. AnnotationURLCitation(end_index=36964, start_index=36775, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=arrhythmogenic%20right%20ventricular%20cardiomyopathy%20type,studies%20that%20describe%20the%20molecular')
  97. AnnotationURLCitation(end_index=37469, start_index=37345, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L78%20TMEM43%20was,12%2C14')
  98. AnnotationURLCitation(end_index=38461, start_index=38305, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=and%20is%20also%20located%20in,of%20mutations%20of%20cardiomyocyte%20junction')
  99. AnnotationURLCitation(end_index=38793, start_index=38619, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=conditions%2C%20similar%20CJ%20localizations%20have,may%20be%20involved%20in%20cardiomyopathies')
  100. AnnotationURLCitation(end_index=39431, start_index=39286, title='Systems genetics analysis defines importance of TMEM43/ LUMA for cardiac- and metabolic-related pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34766515/#:~:text=Broad%20cellular%20functions%20and%20diseases,The%20results%20were')
  101. AnnotationURLCitation(end_index=39604, start_index=39432, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=gender%20and%20vigorous%20exercise%20independently,Electron%20microscopy%2C%20histology')
  102. AnnotationURLCitation(end_index=39927, start_index=39782, title='Systems genetics analysis defines importance of TMEM43/ LUMA for cardiac- and metabolic-related pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34766515/#:~:text=Broad%20cellular%20functions%20and%20diseases,The%20results%20were')
  103. AnnotationURLCitation(end_index=40475, start_index=40314, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=location%20and%20organization,interactions%20to%20the%20intercalated%20disks')
  104. AnnotationURLCitation(end_index=40719, start_index=40558, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=we%20have%20discovered%20that%2C%20in,to%20reconsiderations%20of%20the%20molecular')
  105. AnnotationURLCitation(end_index=41018, start_index=40881, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=cellular%20processes%20,is%20thought%20to%20play%20a')
  106. AnnotationURLCitation(end_index=41354, start_index=41165, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=diminished%20PPARG%20activities%20and%20significantly,suggest%20that%20cardiometabolic%20assessment%20in')
  107. AnnotationURLCitation(end_index=41506, start_index=41355, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=preferential%20loss%20of%20compact%20myocardium,127%5D%2C%20sodium')
  108. AnnotationURLCitation(end_index=41642, start_index=41507, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L472%20and%20fibrosis,109%2C110%2C111')
  109. AnnotationURLCitation(end_index=42022, start_index=41861, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=The%20transmembrane%20protein%2043%20,Serial%20echocardiography%2C%20surface')
  110. AnnotationURLCitation(end_index=42294, start_index=42110, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=in%20TMEM43%20resulting%20in%20emerin,dystrophy%2C%20joint%20contractures%2C%20and%20cardiomyopathy')
  111. AnnotationURLCitation(end_index=42521, start_index=42386, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=p,subjects%2C%20and%20speech%20discrimination%20was')
  112. AnnotationURLCitation(end_index=43048, start_index=42872, title='Systems genetics analysis defines importance of TMEM43/ LUMA for cardiac- and metabolic-related pathways - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34766515/#:~:text=Broad%20cellular%20functions%20and%20diseases,through%20genetic%20regulation%2C%20gene%20pathways')
  113. AnnotationURLCitation(end_index=43983, start_index=43822, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=location%20and%20organization,interactions%20to%20the%20intercalated%20disks')
  114. AnnotationURLCitation(end_index=44086, start_index=43984, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=,Google%20Scholar')
  115. AnnotationURLCitation(end_index=44457, start_index=44296, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=location%20and%20organization,interactions%20to%20the%20intercalated%20disks')
  116. AnnotationURLCitation(end_index=44926, start_index=44765, title='Protein LUMA is a cytoplasmic plaque constituent of various epithelial adherens junctions and composite junctions of myocardial intercalated disks: a unifying finding for cell biology and cardiology - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24770932/#:~:text=we%20have%20discovered%20that%2C%20in,to%20reconsiderations%20of%20the%20molecular')
  117. AnnotationURLCitation(end_index=45351, start_index=45190, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=The%20transmembrane%20protein%2043%20,Serial%20echocardiography%2C%20surface')
  118. AnnotationURLCitation(end_index=45723, start_index=45589, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=More%20recent%20reports%20have%20demonstrated,DSP')
  119. AnnotationURLCitation(end_index=46031, start_index=45891, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=localization%2C%20resulting%20in%20impaired%20cell,This')
  120. AnnotationURLCitation(end_index=46422, start_index=46287, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=p,subjects%2C%20and%20speech%20discrimination%20was')
  121. AnnotationURLCitation(end_index=46601, start_index=46423, title='A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8179140/#:~:text=Auditory%20neuropathy%20spectrum%20disorder%20,passive%20conductance%20current%20in%20cochlear')
  122. AnnotationURLCitation(end_index=46996, start_index=46846, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=ventricular%20,suggest%20that%20cardiometabolic%20assessment%20in')
  123. AnnotationURLCitation(end_index=47158, start_index=46997, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=The%20transmembrane%20protein%2043%20,Serial%20echocardiography%2C%20surface')
  124. AnnotationURLCitation(end_index=47535, start_index=47386, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=Transmembrane%20protein%2043%20,5%20and%20is%20associated%20with')
  125. AnnotationURLCitation(end_index=47671, start_index=47536, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=match%20at%20L472%20and%20fibrosis,109%2C110%2C111')
  126. AnnotationURLCitation(end_index=47992, start_index=47903, title='The TMEM43 S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10190833/#:~:text=,doi')
  127. AnnotationURLCitation(end_index=48155, start_index=47993, title='Transmembrane Protein 43: Molecular and Pathogenetic Implications in Arrhythmogenic Cardiomyopathy and Various Other Diseases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12295021/#:~:text=SCD%20develop%20fibrosis%20with%20fatty,survival%20with%20the%20median%20life')