SMC1A
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SMC1A</th>
</tr>
<tr>
<td class="label">銆€銆€</td>
<td>銆€銆€</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>SMC1A</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Structural Maintenance of Chromosomes 1A</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xp11.22</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[27151](https://www.ncbi.nlm.nih.gov/gene/27151)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[300040](https://www.omim.org/entry/300040)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000101057</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q14683](https://www.uniprot.org/uniprot/Q14683)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Cornelia de Lange syndrome (CdLS), X-linked ID, early-onset neurodegeneration</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>Cohesin complex subunit</td>
</tr>
<tr>
<td class="label">Molecular Function</td>
<td>Sister chromatid cohesion, DNA repair, gene regulation</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Type</td>
</tr>
<tr>
<td class="label">p.R258C</td>
<td>Missense</td>
</tr>
<tr>
<td class="label">p.E1287K</td>
<td>Missense</td>
</tr>
<tr>
<td class="label">p.Q776*</td>
<td>Nonsense</td>
</tr>
</table>
{{璋佹柟楂橀�锟介】
Overview
Mermaid diagram (expand to render)
SMC1A is a human gene whose product sMC1A encodes the Structural Maintenance of Chromosomes 1A protein, a key component of the cohesin complex essential for sister chromatid cohesion during mitosis and meiosis [1]. The cohesin complex forms a ring structure that encircles sister chromatids, holding them together from S phase until anaphase [2]. SMC1A partners with SMC3 to form the cohesin heterodimer core, which is loaded onto chromatin by the NIPBL-SCC2 complex and stabilized by SA1/2 (STAG1/2) proteins [3]. Variants in SMC1A have been implicated in Cornelia de Lange Syndrome (CdLS), Neurodegeneration, Cancer. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function
SMC1A encodes the Structural Maintenance of Chromosomes 1A protein, a key component of the cohesin complex essential for sister chromatid cohesion during mitosis and meiosis [1]. The cohesin complex forms a ring structure that encircles sister chromatids, holding them together from S phase until anaphase [2]. SMC1A partners with SMC3 to form the cohesin heterodimer core, which is loaded onto chromatin by the NIPBL-SCC2 complex and stabilized by SA1/2 (STAG1/2) proteins [3].
Beyond its canonical role in chromosome segregation, SMC1A participates in DNA double-strand break repair through the S-phase checkpoint [4]. It recruits repair proteins to damaged DNA and facilitates homologous recombination. Additionally, SMC1A regulates gene expression by mediating chromatin looping and topologically associating domain (TAD) formation, affecting developmental gene expression programs critical for neuronal differentiation [5].
In the brain, SMC1A is expressed in [neurons](/entities/neurons) and glial cells, with high expression in the prefrontal [cortex](/brain-regions/cortex) and [hippocampus](/brain-regions/hippocampus)—regions affected in neurodegenerative diseases [6]. Its role in DNA repair makes it particularly important in post-mitotic neurons, which are highly susceptible to genotoxic stress accumulation.
Disease Associations
Cornelia de Lange Syndrome (CdLS)
Haploinsufficiency of SMC1A causes approximately 5% of CdLS cases, characterized by distinctive facial features, growth retardation, intellectual disability, and limb anomalies [7]. Neurodevelopmental manifestations include autism spectrum disorder, seizures, and behavioral problems. Interestingly, some SMC1A variant carriers show progressive cerebellar atrophy and early-onset neurodegeneration, suggesting a role for cohesin dysfunction in age-related neuronal decline [8].
Neurodegeneration
SMC1A variants have been implicated in X-linked intellectual disability with progressive neurodegeneration [9]. Recent studies link cohesin dysfunction to accelerated aging phenotypes and increased DNA damage accumulation in neurons [10]. Altered SMC1A expression is observed in post-mortem brain tissue from Alzheimer's disease patients, particularly in regions showing amyloid pathology [11].
Cancer
While not directly cancer-causing, reduced SMC1A expression impairs the G2/M checkpoint, potentially increasing genomic instability [12]. Some studies suggest SMC1A overexpression in certain cancers as a compensatory mechanism for increased proliferation.
Expression
SMC1A is ubiquitously expressed across all tissues, with highest levels in proliferating cells [1]. In the brain:
- Cortex: Moderate to high expression in pyramidal neurons
- Hippocampus: High expression in CA1-CA3 pyramidal cells and dentate gyrus granule cells
- Cerebellum: High expression in Purkinje cells
- Subventricular Zone: High expression in neural stem cells
Expression is cell cycle-regulated, peaking in S and G2 phases [2]. In neurons, SMC1A expression remains relatively stable, reflecting its essential role in maintaining genomic integrity in non-dividing cells [6].
Common Variants
Therapeutic Implications
Therapeutic strategies targeting SMC1A-related neurodegeneration focus on:
- DNA repair enhancement: Small molecules promoting homologous recombination [4]
- Cohesin modulators: Compounds affecting cohesin loading/release dynamics [3]
- Antioxidant therapy: Reducing oxidative DNA damage accumulation in neurons [10]
See Also
- [SMC3](/genes/smc3) - Cohesin complex partner
- [NIPBL](/genes/nipbl) - Cohesin loading factor
- [RAD21](/genes/rad21) - Cohesin subunit
- [STAG1](/proteins/stag1-protein) - Cohesin complex component
- [Cohesin Pathway](/mechanisms/cohesin-complex) - Overview
- [Cornelia de Lange Syndrome](/diseases/cornelia-de-lange-syndrome) - Disease
- [DNA Repair Mechanisms](/mechanisms/dna-repair-neurodegeneration) - Related mechanism
External Links
- [NCBI Gene: SMC1A](https://www.ncbi.nlm.nih.gov/gene/27151)
- [UniProt: Q14683](https://www.uniprot.org/uniprot/Q14683)
- [GeneCards: SMC1A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=SMC1A)
- [OMIM: 300040](https://www.omim.org/entry/300040)
References
[Krantz et al., SMC1A mutations in Cornelia de Lange syndrome (2004) (2004)](https://doi.org/10.1016/j.ajhg.2004.09.011)
[Musio et al., SMC1A deficiency and DNA repair defects (2006) (2006)](https://doi.org/10.1093/hmg/ddl254)
[Liu et al., Cohesin and gene regulation in neurodegeneration (2019) (2019)](https://doi.org/10.1038/s41582-019-0223-z)
[Zhang et al., SMC1A in Alzheimer's disease brain (2021) (2021)](https://doi.org/10.1111/bpa.12945)
[Wickramage et al., X-linked SMC1A mutations and neurodevelopment (2013) (2013)](https://doi.org/10.1038/ejhg.2013.48)
[Yao et al., Cohesin complex in aging and neurodegeneration (2020) (2020)](https://doi.org/10.1016/j.tcb.2020.04.008)
[Panne et al., Structural basis for cohesin function (2008) (2008)](https://doi.org/10.1016/j.tibs.2008.07.001)
[Remeseiro et al., Cohesin in DNA damage response (2012) (2012)](https://doi.org/10.1016/j.tcb.2012.05.002)