Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.
Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3.
Meckel-Gruber syndrome protein MKS3 is required for endoplasmic reticulum-associated degradation of surfactant protein C.
A meckelin-filamin A interaction mediates ciliogenesis.
A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain.
The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway.
TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Structure of the human Meckel-Gruber protein Meckelin.
Interpreting ciliopathy-associated missense variants of uncertain significance (VUS) in Caenorhabditis elegans.
The ciliary transition zone protein TMEM218 synergistically interacts with the NPHP module and its reduced dosage leads to a wide range of syndromic ciliopathies.
RAB3IP stimulates nucleotide exchange on RAB8A
Recruitment of transition zone proteins
CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body
Two functional forms of the Meckel-Gruber syndrome protein TMEM67 generated by proteolytic cleavage by ADAMTS9 mediate Wnt signaling and ciliogenesis
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TMEM67 is a proteolytic substrate of the metalloproteinase ADAMTS9, generating two functional forms: a released N-terminal ectodomain fragment proposed to modulate Wnt signaling and a C-terminal fragment (Delta342) that localizes to the TZ and supports ciliogenesis/TZ assembly.
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Loss of TMEM67 or ADAMTS9 causes reduced recruitment of multiple MKS/B9 module proteins (TCTN1/2/3, TMEM237, CC2D2A, B9D2) to mature basal bodies/TZ, positioning TMEM67 as a central organizer within MKS-related TZ assemblies.
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Cleavage-deficient (non-cleavable) TMEM67 mice retain apparently normal Wnt signaling but show severe ciliogenesis/TZ phenotypes including loss of the TZ necklace formation, supporting mechanistic separability of Wnt-related and TZ-related TMEM67 functions.
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TMEM67 is the most commonly mutated gene in MKS, accounting for approximately 16-20% of MKS cases.
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Patient variants near the TMEM67 cleavage motif (e.g., p.K329T, p.F342V, p.L349S) fail to rescue ciliogenesis/TZ localization in TMEM67 knockout cells and produce strong loss-of-function phenotypes in C. elegans MKS-3 assays, supporting clinical significance of this extracellular region.
Joubert syndrome caused by a TMEM67 mutation - genotype-phenotype analysis
Primary cilia and actin regulatory pathways in renal ciliopathies
An ovine hepatorenal fibrocystic model of a Meckel-like syndrome associated with dysmorphic primary cilia and TMEM67 mutations
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In the ovine TMEM67-associated Meckel-like hepatorenal model, cultured kidney interstitial fibroblasts showed significantly increased primary cilium length in affected animals versus controls (15.1 vs 8.3 micrometers), while ciliation incidence was similar.
Challenges for the implementation of next generation sequencing-based expanded carrier screening - lessons learned from the ciliopathies
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In a carrier screening study of 395 healthy individuals across 118 ciliopathy genes, approximately 11% carried a pathogenic variant, and 50% carried 1-5 strong VUS, highlighting high VUS rates and the need for gene-specific variant interpretation in ciliopathy diagnostics.