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SPECC1L
sperm antigen with calponin homology and coiled-coil domains 1 like
The *SPECC1L* gene provides instructions for producing the cytospin-A protein, which is essential for stabilising microtubules within cells, a process vital for cell migration during embryonic development. The *SPECC1L* gene encodes the cytospin-A protein, playing a critical role in maintaining cell shape and enabling cell migration, particularly during the formation of facial structures in a developing embryo.
SPECC1L is located on the long (q) arm of chromosome 22, at band 22q11.23. Arm ratio per GRCh38 - banding schematic.
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Overview
The *SPECC1L* gene, also known as sperm antigen with calponin homology and coiled-coil domains 1 like, provides the genetic blueprint for a protein called cytospin-A. This protein is a key component in the cell's cytoskeleton, the intricate network that gives cells their structure and plays a role in various cellular activities. Cytospin-A's primary function involves stabilising microtubules [PMID:24075129], which are rigid, hollow fibres that help cells maintain their shape and facilitate cell movement and division.
During embryonic development, precise cell migration is crucial for the correct formation of tissues and organs. The cytospin-A protein is specifically involved in the migration of neural crest cells-cells that originate from the developing spinal cord and travel to specific areas to form diverse structures, including parts of the face.
What the gene does
The cytospin-A protein, encoded by the *SPECC1L* gene, plays a critical role in cellular architecture and dynamics by stabilising microtubules. Microtubules are dynamic structures within the cytoskeleton that are essential for maintaining cell shape, intracellular transport, and cell division. The stabilisation provided by cytospin-A is necessary for microtubules to effectively regulate various cellular processes, including directed cell movement.
Cell migration is fundamental during embryonic development, ensuring that cells move to their correct locations to form tissues and organs. Cytospin-A specifically facilitates cell migration by influencing the elongation of microtubules in a particular direction, which subsequently changes the cell's shape and allows it to move. In the context of embryonic development, cytospin-A is involved in the migration of neural crest cells. These cells originate in the developing spinal cord and migrate to differentiate into various structures, including components of the forehead, nasal bridge, and lower jaw. Therefore, proper function of the cytospin-A protein is vital for normal tissue formation and development [PMID:24075129].
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Chromosome location
The *SPECC1L* gene is located on chromosome 22, specifically at position 22q11.23. This chromosomal band refers to the long (q) arm of chromosome 22, within region 1, band 1, sub-band 2, and sub-sub-band 3. This precise location helps in identifying and studying the gene within the human genome.
Protein structure
The cytospin-A protein, encoded by the *SPECC1L* gene, has a length of 1117 amino acids, featuring several distinct domains [PMID:24075129]. It includes disordered regions, which often lack a fixed three-dimensional structure and are involved in binding to other molecules. These disordered regions are found at amino acids 1-176, 293-323, 358-390, and 920-997. Additionally, the protein contains multiple coiled-coil domains, which are structural motifs typically involved in protein-protein interactions; these are located at amino acids 168-280, 394-449, and 487-807. A Calponin-homology (CH) domain, frequently associated with actin-binding, is situated towards the C-terminus, spanning amino acids 1011-1116.
Key variants
Genetic variations within the *SPECC1L* gene can influence its function. These variations range from single nucleotide changes to larger structural alterations, and are categorised based on their potential impact on protein function. Some variants may be benign, having no noticeable effect, while others can alter the cytospin-A protein's ability to stabilise microtubules or participate in cell migration. Pathogenic variants can disrupt normal cellular processes, potentially leading to developmental conditions. The clinical significance of any identified *SPECC1L* variant is assessed by considering its specific nature and potential impact on protein function.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.3293G>A | p.Arg1098Gln | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.1189A>C | p.Thr397Pro | Pathogenic | ★☆☆☆ | Teebi hypertelorism syndrome |
c.1207A>G | p.Met403Val | Pathogenic | ★☆☆☆ | not provided |
c.1246G>A | p.Ala416Thr | Pathogenic | ★☆☆☆ | Teebi hypertelorism syndrome 1 |
c.1195C>G | p.Arg399Gly | Pathogenic | - | Teebi hypertelorism syndrome 1 |
c.1198_1203del | p.Ile400_His401del | Pathogenic | - | Teebi hypertelorism syndrome |
c.1244A>C | p.Gln415Pro | Pathogenic | - | Oculomaxillofacial dysostosis |
c.1249A>C | p.Thr417Pro | Pathogenic/Likely pathogenic | - | Teebi hypertelorism syndrome |
c.1292T>C | p.Leu431Pro | Likely pathogenic | ★☆☆☆ | Autosomal dominant Opitz G/BBB syndrome |
c.2999A>T | p.Asp1000Val | Likely pathogenic | ★☆☆☆ | Teebi hypertelorism syndrome |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Mutations in the *SPECC1L* gene have been associated with several developmental conditions, primarily those affecting midline structures of the body. One such condition is Opitz G/BBB syndrome, which causes multiple abnormalities including widely spaced eyes (ocular hypertelorism), malformations of the throat that can lead to breathing or swallowing difficulties, brain malformations, characteristic facial features, and genitourinary abnormalities in males. At least two distinct mutations in the *SPECC1L* gene have been identified as causes of Opitz G/BBB syndrome.
Furthermore, *SPECC1L* mutations have been linked to oblique facial clefts, also known as Tessier clefts. These clefts are similar to cleft lip and palate but are generally more severe. The facial clefts can occur on one or both sides of the face.
No disease links recorded for this gene in our reference set.
UK clinical status
The *SPECC1L* gene is included in several NHS Genomic Medicine Service (GMS) panels within the UK, indicating its recognised clinical relevance. It is part of the Clefting panel, the DDG2P panel, the Foetal anomalies panel (R21), the Intellectual disability panel (R29), and the Rare syndromic craniosynostosis or isolated multisuture synostosis panel (R100). Its inclusion across these panels highlights its association with a range of developmental conditions affecting facial structures, intellectual development, and skeletal formation.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
There is no specific lifestyle advice directly linked to the *SPECC1L* gene or its associated conditions. Generally, maintaining a balanced diet, engaging in regular physical activity, and avoiding smoking and excessive alcohol consumption are recommended for overall health and well-being. For individuals or families concerned about genetic conditions, genetic counselling can provide personalised guidance and support.
Supplement considerations
There is no conclusive evidence to suggest that specific supplements can prevent or treat conditions associated with the *SPECC1L* gene. It is always advisable to discuss any concerns about supplement use with a healthcare professional, particularly if considering them for managing a genetic condition.
Frequently asked questions
What is the primary function of the *SPECC1L* gene?
The *SPECC1L* gene provides instructions for the cytospin-A protein, which is crucial for stabilising microtubules within cells. This stabilisation is vital for maintaining cell shape and facilitating cell migration, particularly during embryonic development.
What conditions are associated with mutations in the *SPECC1L* gene?
Mutations in the *SPECC1L* gene are associated with Opitz G/BBB syndrome, which involves midline abnormalities, and oblique facial clefts, also known as Tessier clefts, affecting facial structures.
How does *SPECC1L* relate to embryonic development?
*SPECC1L* plays a key role in the migration of neural crest cells during embryonic development. These cells are essential for forming various structures, including parts of the forehead, nasal bridge, and lower jaw.
Where is the *SPECC1L* gene located?
The *SPECC1L* gene is located on chromosome 22, specifically at position 22q11.23, which is on the long arm of the chromosome.
Is *SPECC1L* included in any UK NHS Genomic Medicine Service panels?
Yes, *SPECC1L* is included in several NHS GMS panels, such as those for Clefting, DDG2P, Foetal anomalies, Intellectual disability, and Rare syndromic craniosynostosis or isolated multisuture synostosis.
References
- Kruszka P, Li D, Harr MH. Mutations in SPECC1L, encoding sperm antigen with calponin homology and coiled-coil domains 1-like, are found in some cases of autosomal dominant Opitz G/BBB syndrome. Journal of medical genetics. 2015. PMID: 25412741
- Gfrerer L, Shubinets V, Hoyos T. Functional analysis of SPECC1L in craniofacial development and oblique facial cleft pathogenesis. Plastic and reconstructive surgery. 2014. PMID: 25357034
- Saadi I, Alkuraya FS, Gisselbrecht SS. Deficiency of the cytoskeletal protein SPECC1L leads to oblique facial clefting. American journal of human genetics. 2011. PMID: 21703590