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SRCAP
Snf2 related CREBBP activator protein
The SRCAP gene encodes a protein integral to chromatin remodelling, a process vital for gene expression and proper cellular development. The SRCAP gene provides instructions for producing the Snf2 related CREBBP activator protein.
SRCAP is located on the short (p) arm of chromosome 16, at band 16p11.2. Arm ratio per GRCh38 - banding schematic.
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The SRCAP gene, also known as Snf2 related CREBBP activator protein, plays a significant role in gene regulation. It is involved in processes that control how DNA is packaged within the cell nucleus, which in turn affects gene expression. Understanding this gene's function helps explain normal human development and certain genetic conditions.
What the gene does
The protein encoded by the SRCAP gene forms part of a larger cellular complex that functions as a chromatin remodeller. This complex alters chromatin structure, which influences how accessible genes are for transcription. Research indicates that the SRCAP protein participates in activating the CREBBP gene. CREBBP produces CREB binding protein, which regulates cellular growth and division processes essential for typical human development. Through its chromatin-modifying activity, SRCAP influences gene expression across multiple biological processes.
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Chromosome location
The SRCAP gene is located on chromosome 16, specifically at position 16p11.2. This genomic address places it within the short arm of chromosome 16 and indicates its involvement in various cellular functions.
Protein structure
The SRCAP protein is quite large, consisting of 3230 amino acids. Disordered regions are present at amino acids 1-71, 253-547, 559-581, 1017-1045, 1058-1125, 1138-1166, 1320-1366, 1406-1425, 1629-1760, 1839-1893, 2214-2233, 2271-2298, 2327-2453, 2564-2583, and 2598-3081. Key functional domains include a HSA domain (amino acids 124-196), a Helicase ATP-binding domain (amino acids 630-795), and a Helicase C-terminal domain (amino acids 2044-2197). Within one of the larger disordered regions, there are two DNA-binding A.T hook domains, located at amino acids 2857-2869 and 2936-2948.
Key variants
Variants within the SRCAP gene can lead to alterations in the protein's structure and function. These changes may impact its role in chromatin remodelling and gene expression. The clinical significance of any specific variant is determined through careful evaluation, considering its effect on protein activity and association with inherited conditions. Variants are often classified based on their predicted impact, ranging from benign to pathogenic.
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.5633dup | p.Pro1879fs | Pathogenic/Likely pathogenic | ★★☆☆ | Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities |
c.6985C>T | p.Arg2329Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Floating-Harbor syndrome |
c.7219C>T | p.Gln2407Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.7255C>T | p.Gln2419Ter | Pathogenic | ★★☆☆ | Floating-Harbor syndrome |
c.7262dup | p.Ser2422fs | Pathogenic/Likely pathogenic | ★★☆☆ | not provided |
c.7303C>T | p.Arg2435Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Floating-Harbor syndrome |
c.7330C>T | p.Arg2444Ter | Pathogenic | ★★☆☆ | Floating-Harbor syndrome |
c.7376del | p.Pro2459fs | Pathogenic/Likely pathogenic | ★★☆☆ | Floating-Harbor syndrome |
c.7382del | p.Pro2461fs | Pathogenic | ★★☆☆ | Floating-Harbor syndrome |
c.7387del | p.Ser2463fs | Pathogenic | ★★☆☆ | not provided |
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
Pathogenic variants in the SRCAP gene are associated with Floating-Harbour syndrome, an inherited condition. This syndrome is characterised by features including short stature, delayed bone age (slowing of bone mineralisation), delayed speech development, and distinctive facial features. Several SRCAP gene mutations have been identified in individuals with this syndrome. Conditions linked to SRCAP typically follow an autosomal dominant inheritance pattern, meaning that inheriting just one altered copy of the gene is sufficient to cause the condition.
Inheritance pattern
Conditions caused by pathogenic SRCAP variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
The SRCAP gene is reviewed by the UK National Health Service (NHS) Genomic Medicine Service. It is listed on several Green panels, indicating strong evidence for its association with specific conditions. These include the DDG2P panel, the Foetal anomalies panel (R21), the Intellectual disability panel (R29), the IUGR and IGF abnormalities panel, and the Monogenic short stature panel (R453).
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Diet & lifestyle considerations
Currently, there are no specific lifestyle interventions known to prevent or treat conditions associated with SRCAP gene variants. General healthy lifestyle recommendations, such as a balanced diet and regular physical activity, are always advisable for overall well-being.
Supplement considerations
There is no conclusive scientific evidence to suggest that any specific supplements can prevent, treat, or mitigate the effects of conditions caused by SRCAP gene variants. Individuals should consult with a healthcare professional before considering any new supplements.
Frequently asked questions
What is the function of the SRCAP gene?
The SRCAP gene provides instructions for a protein that is a key component of a chromatin remodelling complex. This complex modifies DNA packaging, which is crucial for regulating gene expression and ensuring normal cell growth and development.
What condition is associated with the SRCAP gene?
Variants in the SRCAP gene are associated with Floating-Harbour syndrome. This condition typically presents with short stature, delayed bone development, speech delay, and specific facial characteristics.
How is Floating-Harbour syndrome inherited?
Floating-Harbour syndrome, when caused by SRCAP gene variants, follows an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of the altered gene from a parent to develop the condition.
References
- Hood RL, Lines MA, Nikkel SM. Mutations in SRCAP, encoding SNF2-related CREBBP activator protein, cause Floating-Harbor syndrome. American journal of human genetics. 2012. PMID: 22265015
- Slupianek A, Yerrum S, Safadi FF. The chromatin remodeling factor SRCAP modulates expression of prostate specific antigen and cellular proliferation in prostate cancer cells. Journal of cellular physiology. 2010. PMID: 20432434
- Wong MM, Cox LK, Chrivia JC. The chromatin remodeling protein, SRCAP, is critical for deposition of the histone variant H2A.Z at promoters. The Journal of biological chemistry. 2007. PMID: 17617668