Evidence map›Paper›PMID 40436881›Full record

ArticleNature communications2025

Cleavage of the Meckel-Gruber syndrome protein TMEM67 by ADAMTS9 uncouples Wnt signaling and ciliogenesis.

Manu Ahmed, Sydney Fischer, Karyn L Robert, Karen I Lange, Michael W Stuck, Sunayna Best, Colin A Johnson, Gregory J Pazour, Oliver E Blacque, Sumeda Nandadasa

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. The extracellular matrix genebioRxiv : the preprint server for biology · 2026
    Article
  4. Ciliary-Mediated Mechanotransduction in Skeletal Development and Diseases.Results and problems in cell differentiation · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Manu AhmedDepartment of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Sydney FischerDepartment of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-7366-7605
Karyn L RobertDepartment of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Karen I LangeSchool of Biomolecular & Biomedical Science, University College Dublin, Belfield, Ireland.
Michael W StuckProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0003-3387-5850
Sunayna BestDivision of Molecular Medicine, Leeds Institute of Medical Research, The University of Leeds, Leeds, UK.
Colin A JohnsonDivision of Molecular Medicine, Leeds Institute of Medical Research, The University of Leeds, Leeds, UK.ORCID http://orcid.org/0000-0002-2979-8234
Gregory J PazourProgram in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-6285-8796
Oliver E BlacqueSchool of Biomolecular & Biomedical Science, University College Dublin, Belfield, Ireland.ORCID http://orcid.org/0000-0003-1598-2695
Sumeda NandadasaDepartment of Pediatrics, University of Massachusetts Chan Medical School, Worcester, MA, USA. Sumeda.Nandadasa@Umassmed.edu.ORCID http://orcid.org/0000-0002-4954-6376

Funding

Intraflagellar Transport Proteins in MiceR01GM060992 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Gregory J Pazour · 2001 to 2026
$10.3M
Extracellular protease modulation of the cilium transition zone in kidney development and diseaseR01DK126804 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Sumeda Nandadasa · 2022 to 2026
$1.8M
Transmission Electron Microscope for Core EM FacilityS10OD025113 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HENDRICKS, GREGORY · 2018 to 2018
$600k
Scanning Electron Microscope for Core EM FacilityS10RR021043 · NCRR · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI CRAIG, ROGER W · 2007 to 2007
$498k
UltramicrotomeS10OD021580 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HENDRICKS, GREGORY · 2016 to 2016
$53k
NCRR NIH HHS S10 RR021043NIDDK NIH HHS R01 DK126804NIGMS NIH HHS R01 GM060992NIH HHS S10 OD021580NIH HHS S10 OD025113Wellcome Trust
6 · The paper itself

Abstract

TMEM67 mutations cause Meckel-Gruber syndrome and other related ciliopathies. TMEM67 is involved in both ciliary transition zone assembly, and non-canonical Wnt signaling mediated by its extracellular domain. How TMEM67 performs these two separate functions is not known. We identify a cleavage motif in the extracellular domain of TMEM67 cleaved by the extracellular matrix metalloproteinase ADAMTS9. This cleavage regulates the abundance of two functional forms: a C-terminal portion which localizes to the ciliary transition zone regulating ciliogenesis, and a non-cleaved form which regulates Wnt signaling. By characterizing three TMEM67 ciliopathy patient variants within the cleavage motif utilizing mammalian cell culture and C. elegans, we show the cleavage motif is essential for cilia structure and function, highlighting its clinical significance. We generated a non-cleavable TMEM67 mouse model which develop severe ciliopathies phenocopying Tmem67

Indexed as

ADAMTS9 ProteinCiliaCiliary Motility DisordersEncephaloceleMembrane ProteinsPolycystic Kidney DiseasesWnt Signaling PathwayAnimalsCaenorhabditis elegansDisease Models, AnimalHEK293 CellsHumansMiceMice, KnockoutMutationRetinitis PigmentosaADAMTS9 ProteinADAMTS9 protein, humanMembrane ProteinsTMEM67 protein, human

Identifiers

PMID40436881
PMCPMC12119803

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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.