Ask about this productRelated genes to: TMCO4 Blocking Peptide
- Gene:
- TMCO4 NIH gene
- Name:
- transmembrane and coiled-coil domains 4
- Previous symbol:
- -
- Synonyms:
- DKFZp686C23231
- Chromosome:
- 1p36.13
- Locus Type:
- gene with protein product
- Date approved:
- 2005-08-09
- Date modifiied:
- 2014-11-19
Related products to: TMCO4 Blocking Peptide
Related articles to: TMCO4 Blocking Peptide
- Adipocytokines, including leptin, adiponectin, and resistin, are key mediators linking adiposity, insulin resistance, and inflammation. We present the first genome-wide association study (GWAS; N = 5258) and exome-wide association study (ExWAS; N = 4578) on leptin, adiponectin, and resistin in South Asian population. We identified novel associations in genes ZNF467, and LEPREL2 for leptin; ZNF467, LEPREL2, CRLF3, ZNF732, SOX30, XIRP1, ATP8B3, SPATA2L, TMCO4, TLN2, ABCA12, and SHB for adiponectin; and D2HGDH for resistin. Additionally, we confirmed known associations of FTO, MC4R, and HOXB3 with leptin and ADIPOQ with adiponectin. Notably, ADIPOQ variants were consistently significant across GWAS, ExWAS, and gene-based analyses, reinforcing their central role in regulating adiponectin levels. Most of these novel associations identified were population-specific, highlighting the importance of studying diverse populations to uncover unique genetic signals. After adjusting for BMI, the associations with adiponectin and resistin remained significant, whereas most associations for leptin weakened in both effect size and significance. Functional annotation revealed that the identified variants were enriched for expression in adipose tissue, the brain (cerebellar hemisphere and cerebral cortex), and the pituitary gland. These variants act as eQTLs and splice-QTLs in adipose, brain, and pancreas, suggesting cross-tissue regulatory mechanisms. ExWAS further implicated rare variant burden in genes such as LONP1, ZNF335, and TTC16 for adiponectin and resistin. These findings enhance our understanding of adipocytokine biology, emphasises the need for population-specific genetic research, and lays foundation for future functional studies. - Source: PubMed
Publication date: 2025/04/05
Nair Janaki MChauhan GaneshPrasad GauriChakraborty ShraddhaBandesh KhushdeepGiri Anil KMarwaha Raman KBasu AnalabhaTandon NikhilBharadwaj Dwaipayan - Loss of functional RAB18 causes the autosomal recessive condition Warburg Micro syndrome. To better understand this disease, we used proximity biotinylation to generate an inventory of potential RAB18 effectors. A restricted set of 28 RAB18 interactions were dependent on the binary RAB3GAP1-RAB3GAP2 RAB18-guanine nucleotide exchange factor complex. Twelve of these 28 interactions are supported by prior reports, and we have directly validated novel interactions with SEC22A, TMCO4, and INPP5B. Consistent with a role for RAB18 in regulating membrane contact sites, interactors included groups of microtubule/membrane-remodeling proteins, membrane-tethering and docking proteins, and lipid-modifying/transporting proteins. Two of the putative interactors, EBP and OSBPL2/ORP2, have sterol substrates. EBP is a Δ8-Δ7 sterol isomerase, and ORP2 is a lipid transport protein. This prompted us to investigate a role for RAB18 in cholesterol biosynthesis. We found that the cholesterol precursor and EBP-product lathosterol accumulates in both RAB18-null HeLa cells and RAB3GAP1-null fibroblasts derived from an affected individual. Furthermore, de novo cholesterol biosynthesis is impaired in cells in which RAB18 is absent or dysregulated or in which ORP2 expression is disrupted. Our data demonstrate that guanine nucleotide exchange factor-dependent Rab interactions are highly amenable to interrogation by proximity biotinylation and may suggest that Micro syndrome is a cholesterol biosynthesis disorder. - Source: PubMed
Publication date: 2023/09/28
Kiss Robert SChicoine JarredKhalil YoussefSladek RobertChen HePisaturo AlessandroMartin CyrilDale Jessica DBrudenell Tegan AKamath ArchithKyei-Boahen JeffreyHafiane AnouarDaliah GirijaAlecki CéliaHopes Tayah SHeier MartinAligianis Irene ALebrun Jean-JacquesAspden JuliePaci EmanueleKerksiek AnjaLütjohann DieterClayton PeterWills Jimi Cvon Kriegsheim AlexNilsson TommySheridan EamonnHandley Mark T - While genome wide association studies (GWASs) of Alzheimer's Disease (AD) in European (EUR) ancestry cohorts have identified approximately 83 potentially independent AD risk loci, progress in non-European populations has lagged. In this study, data from the Million Veteran Program (MVP), a biobank which includes genetic data from more than 650,000 US Veteran participants, was used to examine dementia genetics in an African descent (AFR) cohort. A GWAS of Alzheimer's disease and related dementias (ADRD), an expanded AD phenotype including dementias such as vascular and non-specific dementia that included 4012 cases and 18,435 controls age 60+ in AFR MVP participants was performed. A proxy dementia GWAS based on survey-reported parental AD or dementia (n = 4385 maternal cases, 2256 paternal cases, and 45,970 controls) was also performed. These two GWASs were meta-analyzed, and then subsequently compared and meta-analyzed with the results from a previous AFR AD GWAS from the Alzheimer's Disease Genetics Consortium (ADGC). A meta-analysis of common variants across the MVP ADRD and proxy GWASs yielded GWAS significant associations in the region of APOE (p = 2.48 × 10), in ROBO1 (rs11919682, p = 1.63 × 10), and RNA RP11-340A13.2 (rs148433063, p = 8.56 × 10). The MVP/ADGC meta-analysis yielded additional significant SNPs near known AD risk genes TREM2 (rs73427293, p = 2.95 × 10), CD2AP (rs7738720, p = 1.14 × 10), and ABCA7 (rs73505251, p = 3.26 × 10), although the peak variants observed in these genes differed from those previously reported in EUR and AFR cohorts. Of the genes in or near suggestive or genome-wide significant associated variants, nine (CDA, SH2D5, DCBLD1, EML6, GOPC, ABCA7, ROS1, TMCO4, and TREM2) were differentially expressed in the brains of AD cases and controls. This represents the largest AFR GWAS of AD and dementia, finding non-APOE GWAS-significant common SNPs associated with dementia. Increasing representation of AFR participants is an important priority in genetic studies and may lead to increased insight into AD pathophysiology and reduce health disparities. - Source: PubMed
Publication date: 2022/12/22
Sherva RichardZhang RuiSahelijo NathanJun GyungahAnglin ToriChanfreau CatherineCho KellyFonda Jennifer RGaziano J MichaelHarrington Kelly MHo Yuk-LamKremen William SLitkowski ElizabethLynch JulieNeale ZoeRoussos PanosMarra DavidMez JesseMiller Mark WSalat David HTsuang DebbyWolf ErikaZeng QingPanizzon Matthew SMerritt Victoria CFarrer Lindsay AHauger Richard LLogue Mark W - We have previously shown that PTHrP(38-94) amide restrains growth and invasion in vitro, causes striking toxicity and accelerates death of some breast cancer cell lines, the most responsive being MDA-MB231, for which tumorigenesis was also attenuated in vivo. We have also demonstrated that mid-region PTHrP gains access to the nuclear compartment of these cells and displays DNA-binding properties in vitro by recognizing targets in both cellular chromatin and isolated oligonucleotides. Here, we examined whether PTHrP(38-94) amide was able to modulate gene expression of MDA-MB231 cells, employing a combination of conventional, differential display and semi-quantitative multiplex PCR techniques. The results obtained provide first evidence that PTHrP(38-94) amide can affect gene expression in tumor cells, identifying A4-differentiation protein/PLP2 as up-regulated, and HOX7/MSX1, COX6C, FZD6, OXR1 and TMCO4 as down-regulated genes in treated cells, and suggest that the cytotoxic activity of the peptide can be ascribed, at least in part, to such transcriptional reprogramming. - Source: PubMed
Sirchia RosaliaLuparello Claudio