Last update 01 Nov 2024

TMC1

Last update 01 Nov 2024

Basic Info

Synonyms

DFNA36, DFNB11, DFNB7

+ [4]

Introduction

Probable ion channel required for the normal function of cochlear hair cells.

Drugs associated with TMC1

Cationic lipid-mediated Cas9–sgRNA complex(Harvard University)

Target

TMC1

Mechanism

TMC1 modulators

Active Org.

Harvard University

Originator Org.

Harvard University

Active Indication

Hearing Loss

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Tmc gene therapy(Harvard Medical School)

Target

TMC1

Mechanism

TMC1 agonists

Active Org.

Harvard Medical School

Originator Org.

Harvard Medical School

Active Indication

Hearing Loss

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TMC1 gene base editing therapy(Broad Institute)

Target

TMC1

Mechanism

TMC1 modulators

Active Org.

The Broad Institute, Inc.

Originator Org.

The Broad Institute, Inc.

Active Indication

Hearing Loss

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TMC1

100 Translational Medicine associated with TMC1

0 Patents (Medical) associated with TMC1

275

Literatures (Medical) associated with TMC1

18 Oct 2024·International journal of audiology

Clinical and genetic characterisation of childhood-onset sensorineural hearing loss reveal associated phenotypes and enrichment of pathogenic founder mutations in the Finnish population.

Article

Author: Pohjola, Pia ; Häkli, Sanna ; Pykälainen, Tyrni ; Kraatari-Tiri, Minna ; Rahikkala, Elisa

OBJECTIVETo examine the clinical and genetic characteristics of childhood-onset bilateral sensorineural hearing loss (SNHL) in Finland.DESIGNRetrospective analysis.STUDY SAMPLEA total of 249 children younger than 18 years were diagnosed with bilateral SNHL in Oulu University Hospital, Finland, from 2017 to 2022.RESULTSPathogenic or likely pathogenic gene variants or chromosome abnormalities explaining SNHL were identified in 41% (N = 101/249) of children. Likely causative variants were more commonly identified in patients with severe SNHL than in those with moderate or mild SNHL. Our study identified likely causative gene variants in 24 different genes and six different likely causative chromosome abnormalities, demonstrating the genetic heterogeneity of SNHL. Population-enriched founder mutations were identified in the CABP2, CLRN1, MYO7A, SUCLA2, TMC1, and TWNK genes. A significant number of patients had associated phenotypes, including global developmental delay or intellectual disability (16%), language disorder (20%), ophthalmological abnormalities (16%), or malformations other than those involving the ear (10%).CONCLUSIONSSNHL is genetically and clinically heterogeneous. Pathogenic variants in GJB2 were the most common. Several population-enriched variants were identified as causing SNHL in the northern Finnish population. Associated medical phenotypes are common and should be taken into account in patients' follow-up and treatment.

01 Sep 2024·Neuron

Sequence variations and accessory proteins adapt TMC functions to distinct sensory modalities

Article

Author: Kang, Lijun ; Zhu, Linhui ; Jiang, Qiang ; Müller, Ulrich ; Zou, Wenjuan ; Li, Shitian ; Qiu, Xufeng

Transmembrane channel-like (TMC) proteins are expressed throughout the animal kingdom and are thought to encode components of ion channels. Mammals express eight TMCs (mTMC1-8), two of which (mTMC1 and mTMC2) are subunits of mechanotransduction channels. C. elegans expresses two TMCs (TMC-1 and TMC-2), which mediate mechanosensation, egg laying, and alkaline sensing. The mechanisms by which nematode TMCs contribute to such diverse physiological processes and their functional relationship to mammalian mTMCs is unclear. Here, we show that association with accessory proteins tunes nematode TMC-1 to divergent sensory functions. In addition, distinct TMC-1 domains enable touch and alkaline sensing. Strikingly, these domains are segregated in mammals between mTMC1 and mTMC3. Consistent with these findings, mammalian mTMC1 can mediate mechanosensation in nematodes, while mTMC3 can mediate alkaline sensation. We conclude that sequence diversification and association with accessory proteins has led to the emergence of TMC protein complexes with diverse properties and physiological functions.

01 Jun 2024·Molecular Genetics & Genomic Medicine

Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants

Article

Author: Zhang, Chuan ; Tian, Xinyuan ; Kang, Qichao ; Wu, Huiyan ; Hui, Ling ; Zhou, Bingbo ; Hao, Shengju ; Chen, Xue ; Ma, Panpan

AbstractBackgroundHearing loss (HL) is the most frequent sensory deficit in humans, with strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counselling for the patient's family.MethodsWe detected and analysed 362 Chinese non‐syndromic HL patients by screening of variants in 15 hot spot mutations. Subsequently, 40 patients underwent further whole‐exome sequencing (WES) to determine genetic aetiology. The candidate variants were verified using Sanger sequencing. Twenty‐three carrier couples with pathogenic variants or likely pathogenic variants chose to proceed with prenatal diagnosis using Sanger sequencing.ResultsAmong the 362 HL patients, 102 were assigned a molecular diagnosis with 52 different variants in 22 deafness genes. A total of 41 (11.33%) cases with the biallelic GJB2 (OMIM # 220290) gene mutations were detected, and 21 (5.80%) had biallelic SLC26A4 (OMIM # 605646) mutations. Mitochondrial gene (OMIM # 561000) mutations were detected in seven (1.93%) patients. Twenty of the variants in 15 deafness genes were novel. SOX10 (OMIM # 602229), MYO15A (OMIM # 602666) and WFS1 (OMIM # 606201) were each detected in two patients. Meanwhile, OSBPL2 (OMIM # 606731), RRM2B (OMIM # 604712), OTOG (OMIM # 604487), STRC (OMIM # 606440), PCDH15 (OMIM # 605514), LOXHD1 (OMIM # 613072), CDH23 (OMIM # 605516), TMC1 (OMIM # 606706), CHD7 (OMIM # 608892), DIAPH3 (OMIM # 614567), TBC1D24 (OMIM # 613577), TIMM8A (OMIM # 300356), PTPRQ (OMIM # 603317), SALL1 (OMIM # 602218), and GSDME (OMIM # 608798) were each detected in one patient. In addition, as regards one couple with a heterozygous variant of CDH23 and PCDH15, respectively, prenatal diagnosis results suggest that the foetus had double heterozygous (DH) variants of CDH23 and PCDH15, which has a high risk to cause ID/F type Usher syndrome.ConclusionOur study expanded the spectrum of deafness gene variation, which will contribute to the genetic diagnosis, prenatal diagnosis and the procreation guidance of deaf couple. In addition, the deafness caused by two genes should be paid attention to in the prenatal diagnosis of families with both deaf patients.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

TMC1

Basic Info

Related

Analysis