Evidence map›Paper›PMID 34766372›Full record

ArticleJournal of clinical laboratory analysis2021

The distal arthrogryposis-linked p.R63C variant promotes the stability and nuclear accumulation of TNNT3.

Jinfang Lu, Huanzheng Li, He Zhang, Zhengxiu Lin, Chenyang Xu, Xueqin Xu, Lin Hu, Zhaotang Luan, Yongliang Lou, Shaohua Tang

Open access · goldAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical laboratory analysis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 37% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Frontiers in cell and developmental biology · 2026
    Review
  2. The EmergingHuman mutation · 2025
    Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Jinfang LuWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
Huanzheng LiKey Laboratory of Birth Defects, Department of Genetics, Wenzhou Central Hospital, Wenzhou, China.
He ZhangZhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, College of Life and Environmental Sciences, Wenzhou University, Wenzhou, China.
Zhengxiu LinThe Second Affiliated Hospital and Yuying Children's Hospital of WMU, School of the Second Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
Chenyang XuKey Laboratory of Birth Defects, Department of Genetics, Wenzhou Central Hospital, Wenzhou, China.
Xueqin XuKey Laboratory of Birth Defects, Department of Genetics, Wenzhou Central Hospital, Wenzhou, China.
Lin HuKey Laboratory of Medical Genetic, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
Zhaotang LuanKey Laboratory of Medical Genetic, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, China.
Yongliang LouWenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, China, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
Shaohua TangKey Laboratory of Birth Defects, Department of Genetics, Wenzhou Central Hospital, Wenzhou, China.ORCID https://orcid.org/0000-0002-2918-8532
Wenzhou Medical University · CNWenzhou Central Hospital · CNWenzhou University · CN

Funding

Medical Scientific Projects from Health Bureau of Zhejiang Province 2019RC275National Key Research and Development Plan of China 2018YFC1002702start-up funding from Wenzhou Medical University QTJ19019Wenzhou Scientific Bureau Y20170020Zhejiang Provincial Natural Science Foundation of China Q16H200001
6 · The paper itself

Abstract

backgroundDistal arthrogryposis (DA) is comprised of a group of rare developmental disorders in muscle, characterized by multiple congenital contractures of the distal limbs. Fast skeletal muscle troponin-T (TNNT3) protein is abundantly expressed in skeletal muscle and plays an important role in DA. Missense variants in TNNT3 are associated with DA, but few studies have fully clarified its pathogenic role.

methodsSanger sequencing was performed in three generation of a Chinese family with DA. To determine how the p.R63C variant contributed to DA, we identified a variant in TNNT3 (NM_006757.4): c.187C>T (p.R63C). And then we investigated the effects of the arginine to cysteine substitution on the distribution pattern and the half-life of TNNT3 protein.

resultsThe protein levels of TNNT3 in affected family members were 0.8-fold higher than that without the disorder. TNNT3 protein could be degraded by the ubiquitin-proteasome complex, and the p.R63C variant did not change TNNT3 nuclear localization, but significantly prolonged its half-life from 2.5 to 7 h, to promote its accumulation in the nucleus.

conclusionThe p.R63C variant increased the stability of TNNT3 and promoted nuclear accumulation, which suggested its role in DA.

Indexed as

Point MutationAmino Acid SubstitutionArginineArthrogryposisCase-Control StudiesCell NucleusChildCysteineFemaleHEK293 CellsHumansMalePregnancyProtein StabilityTroponin TArginineCysteineTNNT3 protein, humanTroponin Tdistal arthrogryposisnuclear accumulationprotein stabilityskeletal muscleTNNT3

Identifiers

PMID34766372
PMCPMC8649346
OpenAlexW3214151540

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.