Evidence map›Paper›PMID 42012498›Full record

ArticleBioscience reports2026

Patient-derived AMOTL1 mutations lead to defective cell migration and tissue development.

Jiaqian Luo, Ruxin Jin, Fang Geng, Yunying Wang, Yuwen Zhu, Wenqiang Gao, Wei Gao, Jian Li, Yaming Jiu, Ruilin Zhang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioscience reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Jiaqian Luo *Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Ruxin Jin *Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Fang Geng *School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Yunying Wang *Institute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Yuwen ZhuInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Wenqiang GaoInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Wei GaoShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Jian LiInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Yaming JiuShanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Ruilin ZhangSchool of Basic Medical Sciences, Wuhan University, Wuhan, China.
Fa-Xing YuInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.ORCID 0000-0003-4834-9335
Yu WangInstitute of Pediatrics, Children's Hospital of Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.ORCID 0000-0003-1070-2818

Funding

MOST | National Natural Science Foundation of China (NSFC) 32200570MOST | National Natural Science Foundation of China (NSFC) 32370770MOST | National Natural Science Foundation of China (NSFC) 32425017MOST | National Natural Science Foundation of China (NSFC) 32570833
6 · The paper itself

Abstract

Angiomotin-like 1 (AMOTL1), by regulating cell-cell junctions, cell polarity, and cell migration, plays a critical role in organogenesis and development. Recently, multiple studies have identified two hotspot mutations in AMOTL1, Arg157 (R157) and Pro160 (P160), in more than ten distinct families presenting with a spectrum of congenital defects, including facial dysmorphisms and cardiac abnormalities. However, the underlying pathogenic mechanism remains elusive. R157 and P160 are located in the highly conserved Tankyrase-binding motif (TBM) of AMOTL1. Here, we show that both the R157C and P160L mutants fail to interact with Tankyrase 1/2 and Ring finger protein 146, rendering them unable to undergo poly ADP-ribosylation, ubiquitination, and subsequent proteasomal degradation. As a result, these mutants are significantly stabilized and accumulate in the cytoplasm. Accumulated AMOTL1 mutants, in turn, disrupt cell junctions and focal adhesions, thereby inhibiting both the velocity and persistence of cell migration. Furthermore, during zebrafish embryonic development, expression of the R157C mutant leads to craniofacial malformations and defects in cardiac function and skeletal muscle. Our study confirms the role of AMOTL1 mutations in tissue development and uncovers the pathogenic mechanism at both molecular and cellular levels.

Indexed as

Cell MovementCraniofacial AbnormalitiesMembrane ProteinsMutationOrganogenesisAngiomotinsAnimalsHEK293 CellsHumansZebrafishAMOTL1 protein, humanAngiomotinsMembrane ProteinsAngiomotin-like 1proteasomesRNF146TNKS1/2

Identifiers

PMID42012498
PMCPMC13161331

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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.