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Analysis of p.Ser549Arg variant, CFTR gene, CF Transmembrane conductance Regulator protein (1480 residues)


Data provided and calculated by CYSMA must be considered as predictions.
They are meant for educational purposes only and are provided with NO WARRANTY with respect to their biological reliability.



  • Allele frequency:

    variant S549R gnomAD (123,136 exomes): 3.99e-06
    variant S549N gnomAD (123,136 exomes): 8.77e-05; variant S549N gnomAD (15,496 genomes): 6.37e-05
    variant S549R gnomAD (123,136 exomes): 7.97e-06


  • Ortholog conservation: Help


    Number of sequences AAPI* AAPIR** Number of divergencies Number of mutant R549 Number of gaps Conservation of S549 Conservation - gap
    50 80.72% 90.13% 0
    show divergencies    		 0
    details    		 0
    details    		 100.00% (50 / 50) 100.00% (50 / 50)


    The wild-type residue S549 is conserved at 100% among the CFTR orthologs

    *AAPI: Alignment Average Percentage Identity
    **AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 549). AAPIR appears in green if it is more than 10% compared to AAPI, in red if less than 10%.
    Click here for more details on the alignment.



    CYSMA's visualizing modules for Ortholog conservation:





    ⬇ Download the region alignment (50 residues, Fasta format)
    ⬇ Download the CFTR phylogenic tree



    Display methods


  • Domain conservation: Help

    The domain NBD1 of CF Transmembrane conductance Regulator has been shown to interact with:



    The residue p.Ser549 (NBD1) seems to play a key role in the CFTR function:

    p.Ser549 belongs to the signature motif (LSGGQ) and is located in the consensus ATPase binding site.


    The residue p.Ser549 belongs to the domain NBD1.

    423
    		649


    NBD1: is the nucleotide binding domain 1, also called the ATP-binding cassette (ABC). It contains the Walker A (P-loop) and Walker B motifs, the C-motif (also known as the signature sequence), the A-, D-, Q-, and H-loops.








    NBD1 of CF Transmembrane conductance Regulator domain alignment including p.Ser549 residue.



    Number of sequences AAPID***
    (from aa 423 to aa 649)    		 AAPIR! Number of divergencies Number of mutant Number of gaps Conservation of S549 Conservation - gap
    3982 26.61% 40.58% 142
    show divergencies    		 2 3 96.36% (3837 / 3982) 96.43% (3837 / 3979)



    ***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
    !AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 549). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.

    The wild-type residue S549 belongs to the NBD1 domain and is conserved at 96.36% among the NBD1 homologs (3837 / 3982 NBD1 homologs)
    The variant S549R has been found among the NBD1 homologs with a non significant frequency: 0.05% (2 / 3982 NBD1 homologs)

    Divergencies show the amino acids which have been selected in the evolution. Residues present in more than 10% of the sequences are highlighted in blue.
    Please note that CYSMA does not consider splicing alterations.
    Refer to the Help page for more details.



    CYSMA's visualizing modules for NBD1 domain conservation:



    ⬇ Download the domain alignment (Clustal) ⬇ Download the region alignment (50 residues, Fasta)


    Display methods


    • Refer to the Help page for more details.


  • Secondary structure analysis: Help


    Residue p.Ser549 is predicted to belong to a loop. Probability is 0.927.

    Direct environment is as follow:

    GITLS549GGQR
    CCCCCHHHH


    Display methods











  • 3D analysis: Help


    Models provided and analysed by CYSMA must be considered as predictions, therefore be careful when interpreting the results. All efforts have been made to build structures of quality, however, they are provided with NO WARRANTY as to their accuracy with the real biological molecules studied.

    Wild type and predicted mutant structures have been compared. You will find the results below.


  • Clinical significance:

    The variant S549R has been been described as Pathogenic, drug response - reviewed by expert panel - (ClinVar for more details)


  • Patients data: CFTR-France


    • Variant S549R might correspond to:


    Variant details from CFTR-France:
    Name NM_000492.3:c.1645A>C
    Protein name NP_000483.3:p.(Ser549Arg)
    Genomic name chr7:g.117227853A>C
    Class disease-causing


    Patients carrying this variant in CFTR-France:
    Total number of patients 2
    CF 1
    CFTR-RD1
    • CBAVD  1

    (CFTR-France for more details)




  • Additional resources:



    • References


    CYSMA has completed its calculations; Execution time: 14 wallclock secs (10.41 usr 0.04 sys + 2.85 cusr 0.06 csys = 13.36 CPU)





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