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CHUVLMUM




Analysis of p.Gly85Glu 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 G85E gnomAD (123,136 exomes): 3.99e-05; variant G85E gnomAD (15,496 genomes): 3.19e-05


  • Ortholog conservation: Help


    Number of sequences AAPI* AAPIR** Number of divergencies Number of mutant E85 Number of gaps Conservation of G85 Conservation - gap
    50 80.72% 86.95% 1
    show divergencies
    0
    details
    0
    details
    98.00% (49 / 50) 98.00% (49 / 50)


    The wild-type residue G85 is highly conserved among the CFTR orthologs: 98% (49 / 50 CFTR orthologs)
    The variant G85E has never been found among the CFTR orthologs

    *AAPI: Alignment Average Percentage Identity
    **AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 85). 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 MSD1 of CF Transmembrane conductance Regulator has been shown to interact with:



    The residue p.Gly85 (MSD1) seems to play a key role in the CFTR function:

    p.Gly85 is involved in the CFTR folding.


    The residue p.Gly85 belongs to the domain MSD1.

    69
    422


    MSD1: is the membrane-spanning domain 1, composed of six transmembrane helices (TM1-TM6).
    Four of the six TMs protrude into the cytosol to form the intracellular loops ICL1 (between TM2 and TM3) and ICL2 (between TM4 and TM5). ICL1 contacts NBD1 at the level of the ATP-binding site, while ICL2 binds in a groove located at the surface of NBD2.








    MSD1 of CF Transmembrane conductance Regulator domain alignment including p.Gly85 residue.



    Number of sequences AAPID***
    (from aa 69 to aa 422)
    AAPIR! Number of divergencies Number of mutant Number of gaps Conservation of G85 Conservation - gap
    429 17.13% 14.39% 337
    show divergencies
    1 14 18.18% (78 / 429) 18.80% (78 / 415)



    ***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
    !AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 85). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.

    The wild-type residue G85 belongs to the MSD1 domain and is conserved at 18.18% among the MSD1 homologs (78 / 429 MSD1 homologs)
    The variant G85E has been found among the MSD1 homologs with a non significant frequency: 0.23% (1 / 429 MSD1 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 MSD1 domain conservation:





    Display methods


  • Refer to the Help page for more details.


  • Secondary structure analysis: Help


    Residue p.Gly85 is predicted to belong to an α helice. Probability is 0.991.

    Direct environment is as follow:

    FMFYG85IFLY
    HHHHHHHHH


    Observed frequencies in α helices:
    G: 0.76
    E: 1.2

    Mutant residue is more observed in this type of structure.

    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 G85E has been been described as Pathogenic - practice guideline - (ClinVar for more details)


  • Patients data: CFTR-France

  • Variant G85E might correspond to:


    Variant details from CFTR-France:
    Name NM_000492.3:c.254G>A
    Protein name NP_000483.3:p.(Gly85Glu)
    Genomic name chr7:g.117149177G>A
    Class disease-causing


    Patients carrying this variant in CFTR-France:
    Total number of patients 35
    CF 27
    CFTR-RD7
    • Bronchiectasis  1
    • CBAVD  3
    • CRS-NP  2
    • Pancreatitis  1
    Pending (NBS) 1

    (CFTR-France for more details)




  • Additional resources:



  • References


    CYSMA has completed its calculations; Execution time: 23 wallclock secs (17.26 usr 0.06 sys + 5.14 cusr 0.09 csys = 22.55 CPU)