Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 1Genomics and Rare DiseasesProtein Structure and DynamicsEnzyme Structure and Function

The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.

Molecular Origins of the Mendelian Rare Diseases Reviewed by Orpha.net: A Structural Bioinformatics Investigation

Open access
Visibelli, Anna, Finetti, Rebecca, Niccolai, Neri, Spiga, Ottavia, Santucci, Annalisa·2024·International Journal of Molecular Sciences
DOI 10.3390/ijms25136953PMC PMC11241713

Published version of a preprint

Open this paper in CoChat — free account

Abstract

The study of rare diseases is important not only for the individuals affected but also for the advancement of medical knowledge and a deeper understanding of human biology and genetics. The wide repertoire of structural information now available from reliable and accurate prediction methods provides the opportunity to investigate the molecular origins of most of the rare diseases reviewed in the Orpha.net database. Thus, it has been possible to analyze the topology of the pathogenic missense variants found in the 2515 proteins involved in Mendelian rare diseases (MRDs), which form the database for our structural bioinformatics study. The amino acid substitutions responsible for MRDs showed different mutation site distributions at different three-dimensional protein depths. We then highlighted the depth-dependent effects of pathogenic variants for the 20,061 pathogenic variants that are present in our database. The results of this structural bioinformatics investigation are relevant, as they provide additional clues to mitigate the damage caused by MRD.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/ijms25136953

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 The Orphanetta workflow.
Figure 1 The Orphanetta workflow.CC BY · PubMed Central
Figure 2 Amino acid distributions of missense pathogenic variants reviewed by Opha.net dataset. Rows describe how each of the natural amino acids has been replaced by column residues. Colors refer to the number of codon nucleotides involved in mutations: green, yellow, and red indicate, respectively, one-, two-, and three-nucleotide changes.
Figure 2 Amino acid distributions of missense pathogenic variants reviewed by Opha.net dataset. Rows describe how each of the natural amino acids has been replaced by column residues. Colors refer to the number of codon nucleotides involved in mutations: green, yellow, and red indicate, respectively, one-, two-, and three-nucleotide changes.CC BY · PubMed Central
Figure 3 The sterical distribution of mutation sites in MRD proteins of our dataset. Structural data are clustered according to the POPS algorithm [4], and the Q(SASA) parameter categorizes the 20.248 mutation sites as follows: (i) fully buried < 0.15; (ii) internal > 0.15 and <0.24; (iii) intermediate > 0.24 and <0.60; (iv) external > 0.60 and <0.80; and (v) fully solvent-exposed > 0.8.
Figure 3 The sterical distribution of mutation sites in MRD proteins of our dataset. Structural data are clustered according to the POPS algorithm [4], and the Q(SASA) parameter categorizes the 20.248 mutation sites as follows: (i) fully buried < 0.15; (ii) internal > 0.15 and <0.24; (iii) intermediate > 0.24 and <0.60; (iv) external > 0.60 and <0.80; and (v) fully solvent-exposed > 0.8.CC BY · PubMed Central
Figure 4 Profile of amino acid replacements in the structurally defined proteins that are responsible for MRD. Histograms refer to percent of amino acid variations in the fully buried and fully exposed regions, respectively, in black and grey colors.
Figure 4 Profile of amino acid replacements in the structurally defined proteins that are responsible for MRD. Histograms refer to percent of amino acid variations in the fully buried and fully exposed regions, respectively, in black and grey colors.CC BY · PubMed Central
Figure 5 Amino acid replacement matrices of fully buried (a) and fully exposed (b) pathogenic variants. As in Figure 3, rows describe how each of the natural amino acids has been replaced by column residues.
Figure 5 Amino acid replacement matrices of fully buried (a) and fully exposed (b) pathogenic variants. As in Figure 3, rows describe how each of the natural amino acids has been replaced by column residues.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 24 references

Metadata

Authors
Visibelli, A., Finetti, R., Niccolai, N., Spiga, O., & Santucci, A.
Affiliations
University of Siena (IT)
Corresponding author
Niccolai, Neri
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2024-06-25
Volume
25
Issue
13
Pages
6953
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms25136953
PMC
PMC11241713
OpenAlex
W4400092293
Cited by
1
References
24
Citations by year
2025: 1
FWCI
0.27
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Use Siena air (University of Siena) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
protein structure, amino acid substitutions, structural bioinformatics
MeSH terms
Humans, Models, Molecular, Protein Conformation, Proteins, Computational Biology, Amino Acid Substitution, Mutation, Missense, Databases, Genetic, Rare Diseases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Molecular Origins of the Mendelian Rare Diseases Reviewed by Orpha.net: A Structural Bioinformatics Investigation. https://app.cochat.ai/papers/10.3390/ijms25136953
The paper
Visibelli, A., Finetti, R., Niccolai, N., Spiga, O., & Santucci, A. (2024). Molecular Origins of the Mendelian Rare Diseases Reviewed by Orpha.net: A Structural Bioinformatics Investigation. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms25136953

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.