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Analysis of p.Leu53Val 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: |
Ortholog conservation: |
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Number of sequences | AAPI* | AAPIR** | Number of divergencies | Number of mutant V53 | Number of gaps | Conservation of L53 | Conservation - gap |
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50 | 80.72% | 84.56% | 1 show divergencies |
0 details |
0 details |
98.00% (49 / 50) | 98.00% (49 / 50) |
The wild-type residue L53 is highly conserved among the CFTR orthologs: 98% (49 / 50 CFTR orthologs) The variant L53V 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 53). 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
Domain conservation: |
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The domain N-ter of CF Transmembrane conductance Regulator has been shown to interact with:
The residue p.Leu53 belongs to the domain N-ter.
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N-ter of CF Transmembrane conductance Regulator domain alignment including p.Leu53 residue.
Number of sequences | AAPID*** (from aa 1 to aa 68) |
AAPIR! | Number of divergencies | Number of mutant | Number of gaps | Conservation of L53 | Conservation - gap |
---|---|---|---|---|---|---|---|
123 | 35.55% | 31.12% | 44 show divergencies |
1 | 2 | 62.60% (77 / 123) | 63.64% (77 / 121) |
***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
!AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 53). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.
The wild-type residue L53 belongs to the N-ter domain and is conserved at 62.60% among the N-ter homologs (77 / 123 N-ter homologs)
The variant L53V has been found among the N-ter homologs with a non significant frequency: 0.81% (1 / 123 N-ter 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 N-ter domain conservation:
Refer to the Help page for more details.
Secondary structure analysis: |
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Residue p.Leu53 is predicted to belong to an α helice. Probability is 0.986.
Direct environment is as follow:
L | S | E | K | L53 | E | R | E | W |
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Observed frequencies in α helices:
L: 1.16
V: 0.88
Mutant residue is less observed in this type of structure.
3D analysis: |
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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.
PDB template | Sequence identity* | MolProbity bad rotamers | MolProbity Ramachandran outliers | MolProbity Ramachandran favored |
---|---|---|---|---|
5UAK | 99.8 % | 18/1313 - 1.37 % | 17/1478 - 1.15 % | 1360/1478 - 92.2 % |
Click on the MolProbity logo for complete details on the structure quality
CYSMA's modules to download the 3D structures:
CYSMA's 3D Automatic Annotation:
WARNING! The experimental 3D structure used for our predictions is the complete human CFTR structure which have been solved at a 3.7 Å resolution using cryo-electron microscopy (PDB: 5UAK; Liu et al. 2017). The overall resolution is fairly low so the CYSMA's 3D Automatic Annotation pipeline might have missed some important structural effects.
L53 | V53 |
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none | none |
L53 | V53 |
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4.96 Å between LEU 53 CB and ALA 155 CB 4.03 Å between LEU 53 CG and ALA 155 CB 3.34 Å between LEU 53 CD1 and ALA 155 CB 4.81 Å between LEU 53 CG and PHE 77 CE2 4.74 Å between LEU 53 CD2 and PHE 77 CD2 4.54 Å between LEU 53 CD2 and CYS 76 CB 4.25 Å between LEU 53 CD1 and LEU 73 CD1 4.39 Å between LEU 53 CD2 and LEU 73 CD1 3.80 Å between LEU 53 CB and LEU 159 CD1 4.70 Å between LEU 53 CG and LEU 159 CD1 4.25 Å between LEU 53 CD1 and LEU 159 CD1 | 4.80 Å between VAL 53 CB and ALA 155 CB 4.31 Å between VAL 53 CG1 and ALA 155 CB 4.09 Å between VAL 53 CG2 and ALA 155 CB 4.17 Å between VAL 53 CG1 and PHE 77 CE2 4.26 Å between VAL 53 CB and LEU 159 CD1 4.79 Å between VAL 53 CG2 and LEU 159 CB |
For hydrophobic effects, the important point is the number of residues involved more than the number of interactions.
L53 | V53 |
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none | none |
CYSMA's 3D visualizing module:
L53 (wild-type) | V53 (mutant) |
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JSmol Legends: The residue at the position 53 is located in the center, labelled in yellow and surrounded by its neighboring residues (distance < 5 Å). Van der Waals contacts with the residue 53 are represented by dotted lines. Amino acids involved in H-bonds with the residue 53 are labelled in blue. Amino acids involved in steric clashes with the residue 53 are labelled in red.
Display JSmol complete legends
Display Molecular Modelling methods
Refer to the Help page for more details.Clinical significance: |
Patients data: CFTR-France |
Variant L53V might correspond to:
Name | NM_000492.3:c.157T>G |
Protein name | NP_000483.3:p.(Leu53Val) |
Genomic name | chr7:g.117144410T>G |
Class | unclassified |
Total number of patients | 1 |
CFTR-RD | 1
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(CFTR-France for more details)
Additional resources: |
The variation is not reported in Uniprot.
CYSMA Report: |
CFTR orthologs conservation | The wild-type residue L53 is highly conserved among the CFTR orthologs: 98% (49 / 50 CFTR orthologs)The variant L53V has never been found among the CFTR orthologs |
N-ter homologs conservation | The wild-type residue L53 belongs to the N-ter domain and is conserved at 62.60% among the N-ter homologs (77 / 123 N-ter homologs)
The variant L53V has been found among the N-ter homologs with a non significant frequency: 0.81% (1 / 123 N-ter homologs) |
Structural effects | The wild-type residue LEU is buried and is likely to belong to a hydrophobic pocket or core. This hydrophobic core is reduced in the mutant residue VAL, which might slightly destabilize the region |
Allele frequency | The variant has not been reported in gnomAD |
Clinical significance | The variant L53V has not been reported in ClinVar |
CFTR-France | The variant L53V might correspond to: NM_000492.3:c.157T>G, which is reported to be unclassified ( CFTR-France for more details) |
Additional resources | SIFT prediction: variant L53V is predicted to be tolerated (score: 0.1) PPH2 prediction: variant L53V is predicted to be damaging (score: 0.999) |
CYSMA has completed its calculations; Execution time: 12 wallclock secs ( 7.91 usr 0.03 sys + 3.05 cusr 0.04 csys = 11.03 CPU)