Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Primate-Specific Non-coding Variant in PTPRD Gene Drives Developmental Dysplasia of the Hip

ABSTRACT: This project investigates the molecular mechanisms underlying developmental dysplasia of the hip (DDH). Specifically, it explores how a primate-specific non-coding variant in the PTPRD gene drives DDH pathogenesis through the regulation of the CSNK2A1-AMBRA1 mitophagy axis.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Shaoting Luo

PROVIDER: PXD080962 | iProX | Mon Jul 13 00:00:00 GMT+01:00 2026

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

Functional characterization of the novel GWAS-identified GP2 coding variant

Project description:Functional characterization of the novel GWAS-identified GP2 coding variant

| PRJNA614018 | ENA

TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy

Project description:TMEM106B is a risk modifier for a growing list of age-associated dementias including Alzheimer's and frontotemporal dementia, yet its function remains elusive. Two key questions that emerge from past work are whether the conservative T185S coding variant found in the minor haplotype contributes to protection, and whether the presence of TMEM106B is helpful or harmful in the context of disease. Here we address both issues while extending the testbed for study of TMEM106B from models of TDP to tauopathy. We show that TMEM106B deletion accelerates cognitive decline, hindlimb paralysis, neuropathology, and neurodegeneration. TMEM106B deletion also increases transcriptional overlap with human AD, making it a better model of disease than tau alone. In contrast, the coding variant protects against tau-associated cognitive decline, neurodegeneration, and paralysis without affecting tau pathology. Our findings show that the coding variant contributes to neuroprotection and suggest that TMEM106B is a critical safeguard against tau aggregation.

2025-08-05 | GSE223376 | GEO

A rare non-coding enhancer variant in SCN5A contributes to the high prevalence of Brugada syndrome in Thailand

Project description:Brugada syndrome (BrS) is a cardiac arrhythmia disorder that causes sudden death in young adults. Rare genetic variants in the SCN5A gene, encoding the Nav1.5 sodium channel, and common non-coding variants at this locus, are robustly associated with the condition. BrS is particularly prevalent in Southeast Asia but the underlying ancestry-specific factors remain largely unknown. Methods: Genome sequencing of BrS probands and population-matched controls from Thailand was performed to identify rare non-coding variants at the SCN5A-SCN10A locus that were enriched in BrS cases. A likely causal variant was prioritised by computational methods and introduced into human pluripotent stem cell (hiPSC) lines using CRISPR-Cas9. The effect of the variant on SCN5A expression and Nav1.5 sodium channel current was then assessed in hiPSC-derived cardiomyocytes (hiPSC-CMs). Results: A rare non-coding variant in an SCN5A intronic enhancer region was highly enriched in BrS cases (detected in 3.9% of cases with a case-control odds ratio of 45.2). The variant affects a nucleotide conserved across all mammalian species and predicted to disrupt a Mef2 transcription factor binding site. Heterozygous introduction of the enhancer variant in hiPSC-CMs caused significantly reduced SCN5A expression from the variant-containing allele and a 30% reduction in Nav1.5-mediated sodium current density compared to isogenic controls, confirming its pathogenicity. Patients with the variant had severe phenotypes, with 89% experiencing cardiac arrest. Conclusions: This is the first example of a functionally validated rare non-coding variant at the SCN5A locus and highlights how genome sequencing in understudied populations can identify novel disease mechanisms. The variant partly explains the increased prevalence of BrS in this region and enables the identification of at-risk variant carriers to reduce the burden of sudden cardiac death in Thailand.

2025-01-02 | GSE264359 | GEO

New RHD variant

Project description:A new RHD variant the non-coding sequence

| PRJEB27722 | ENA

The TMEM106B T186S coding variant increases neurite arborization and synaptic density in primary hippocampal neurons

Project description:The lysosomal protein TMEM106B was identified as a risk modifier of multiple dementias including frontotemporal dementia and Alzheimer's disease. The gene comes in two major haplotypes, one associated with disease risk, and by comparison, the other with protection. Only one coding polymorphism distinguishes the alleles, a threonine-to-serine substitution at residue 185 (186 in mouse). Transcriptional studies suggest synaptic, neuronal, and cognitive preservation in subjects with the protective haplotype, while in vitro studies revealed dramatic effects of TMEM106B deletion on neuronal development. Despite this background, the field has not yet resolved whether coding variant is biologically meaningful, and if so, whether it has any specific effect on neuronal phenotypes. Here we studied how loss of TMEM106B or expression of the lone coding variant affected transcriptional signatures in the mature brain and neuronal structure during development in primary neurons. We show that homozygous expression of the TMEM106B T186S variant in knock-in mice increased cortical expression of genes associated with excitatory synaptic function and axon outgrowth, and promoted neurite branching, dendritic spine density, and synaptic density in primary hippocampal neurons. In contrast, constitutive TMEM106B deletion affected transcriptional signatures of myelination without altering neuronal development in vitro. Our findings show that the T186S variant is functionally relevant and may contribute to disease resilience during neurodevelopment.

2023-11-02 | GSE240156 | GEO

Non-coding autoimmune risk variant accelerates T peripheral helper cell development via ICOS

Project description:Fine-mapping and functional studies implicate rs117701653, a common non-coding variant in the CD28/CTLA4/ICOS locus, as a contributor to risk for rheumatoid arthritis and type 1 diabetes. Using DNA pulldown, mass spectrometry, genome editing and eQTL analysis, we establish that the disease-associated allele reduces affinity for the inhibitory chromosomal regulator SMCHD1 to drive expression of inducible T-cell costimulator (ICOS), enhancing memory CD4+ T cell ICOS expression in individuals bearing the risk allele. Higher ICOS expression is paralleled by an increase in circulating T peripheral helper (Tph) cells, and in rheumatoid arthritis patients, of blood and joint fluid Tph cells and circulating plasmablasts, suggesting a causal link. Indeed, ICOS ligation accelerates T cell differentiation into CXCR5-PD-1high Tph cells producing IL-21 and CXCL13, as does carriage of the rs117701653 risk allele. Thus, mechanistic dissection of a causal non-coding variant in human autoimmunity discloses a new pathway through which ICOS regulates Tph abundance.

2023-07-01 | GSE235868 | GEO

Transcriptionally inactive ATF2 variant drives melanomagenesis

Project description:Transcriptionally inactive ATF2 variant drives melanomagenesis

| PRJNA320278 | ENA

Regulatory impact of a 5’UTR resident Single Nucleotide Variant on EDN1 gene expression and RNA-protein interactions

Project description:Non-coding regulatory variants are gaining a lot of attention in recent years. This study identifies a 5’UTR variant of the Endothelin-1 gene (EDN1) linked to elevated production of Endothelin-1. The potent vasoactive Endothelin-1 (ET-1) peptide is implicated in vascular homeostasis. Its dysregulated production disturbs the balance between vasodilation and vasoconstriction with pathophysiological consequences including cardiovascular diseases. In an observational study with 95 CAD patients two were identified as homozygous for an insertion of ‘A’ at +139 position of 5’UTR region of EDN1 gene. These patients exhibited elevated median plasma ET-1 levels (16.02 pg/ml), compared to 6.6 pg/ml and 3.87 pg/ml observed in patients without the insertion in the homozygous and heterozygous states, respectively. This clinical observation, uninformative statistically, was verified in vitro through reporter assays that demonstrated a significant increase in ET-1 expression. RNA affinity pull-down coupled with MS/MS was further employed to delineate differential RNA protein interactions. Proteomic profiling identified recruitment of RNA-binding proteins by the insertion variant. Collectively, these findings implicate the +139 A insertion in the EDN1 5′-UTR as a functional non-coding variant that primarily enhances ET-1 expression through post-transcriptional mechanisms, including translation efficiency and mRNA stability, thereby influencing cardiovascular disease risk.

2026-06-01 | PXD076288 | Pride

Non-coding autoimmune risk variant accelerates T peripheral helper cell development via ICOS

Project description:Non-coding autoimmune risk variant accelerates T peripheral helper cell development via ICOS

| PRJNA987728 | ENA

satmut_utils: a simulation and variant calling package for multiplexed assays of variant effect

Project description:We use stable expression of a cystathionine-beta synthase (CBS) variant library in HEK293T cells to identify CBS coding sequence variants that alter mRNA abundance

2022-04-22 | GSE201057 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data