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Analysis of p.Leu1480Pro 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 P1480 | Number of gaps | Conservation of L1480 | Conservation - gap |
---|---|---|---|---|---|---|---|
50 | 80.72% | 69.77% | 1 show divergencies |
0 details |
1 details |
96.00% (48 / 50) | 97.96% (48 / 49) |
The wild-type residue L1480 is highly conserved among the CFTR orthologs: 96% (48 / 50 CFTR orthologs) The variant L1480P 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 1480). 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 C-ter of CF Transmembrane conductance Regulator has been shown to interact with:
The residue p.Leu1480 (C-ter) seems to play a key role in the CFTR function:
p.Leu1480 belongs to the PDZ-binding motif.
The residue p.Leu1480 belongs to the domain C-ter.
1444 |
| 1480 |
|
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C-ter of CF Transmembrane conductance Regulator domain alignment including p.Leu1480 residue.
Number of sequences | AAPID*** (from aa 1444 to aa 1480) |
AAPIR! | Number of divergencies | Number of mutant | Number of gaps | Conservation of L1480 | Conservation - gap |
---|---|---|---|---|---|---|---|
22 | 62.20% | 78.63% | 0 show divergencies |
0 | 1 | 95.45% (21 / 22) | 100.00% (21 / 21) |
***AAPID: Alignment Average Percentage Identity of the Domain (positions are indicated).
!AAPIR: Alignment Average Percentage Identity of the Region (20 residues surrounding position 1480). AAPIR appears in green if it is more than 10% compared to AAPID, in red if less than 10%.
The wild-type residue L1480 is conserved at 95.45% among the C-ter domain 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 C-ter domain conservation:
Refer to the Help page for more details.
Secondary structure analysis: |
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Residue p.Leu1480 is predicted to belong to a loop. Probability is 0.981.
Direct environment is as follow:
V | Q | D | T | R | L1480 |
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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 |
---|---|---|---|---|
model de novo (Modelller) | 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.
L1480 | P1480 |
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none | none |
L1480 | P1480 |
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2.53 Å between LEU 1480 OX and GLN 1476 NE2 | none |
CYSMA's 3D visualizing module:
L1480 (wild-type) | P1480 (mutant) |
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JSmol Legends: The residue at the position 1480 is located in the center, labelled in yellow and surrounded by its neighboring residues (distance < 5 Å). Van der Waals contacts with the residue 1480 are represented by dotted lines. Amino acids involved in H-bonds with the residue 1480 are labelled in blue. Amino acids involved in steric clashes with the residue 1480 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 L1480P might correspond to:
Name | NM_000492.3:c.4439T>C |
Protein name | NP_000483.3:p.(Leu1480Pro) |
Genomic name | chr7:g.117307158T>C |
Class | unclassified |
Total number of patients | 1 |
CFTR-RD | 1
|
(CFTR-France for more details)
Additional resources: |
The variation is not reported in Uniprot.
CYSMA Report: |
CFTR orthologs conservation | The wild-type residue L1480 is highly conserved among the CFTR orthologs: 96% (48 / 50 CFTR orthologs)The variant L1480P has never been found among the CFTR orthologs |
C-ter homologs conservation | The wild-type residue L1480 is conserved at 95.45% among the C-ter domain homologs |
Structural effects | |
Allele frequency | The variant L1480P in gnomAD (123,136 exomes): 3.99e-06 |
Clinical significance | The variant L1480P has not been reported in ClinVar |
CFTR-France | The variant L1480P might correspond to: NM_000492.3:c.4439T>C, which is reported to be unclassified ( CFTR-France for more details) |
Additional resources | SIFT prediction: variant L1480P is predicted to be damaging (score: 0) PPH2 prediction: variant L1480P is predicted to be damaging (score: 1) |
CYSMA has completed its calculations; Execution time: 12 wallclock secs ( 8.45 usr 0.04 sys + 3.58 cusr 0.06 csys = 12.13 CPU)