Affinage

TMEM107

Transmembrane protein 107 · UniProt Q6UX40

Length
140 aa
Mass
15.5 kDa
Annotated
2026-06-10
22 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TMEM107 is a transmembrane protein of the ciliary transition zone (TZ) that organizes the MKS ciliopathy module to control ciliary protein composition and Hedgehog signal transduction (PMID:26595381, PMID:26518474). Within the TZ it occupies an intermediate layer of the MKS module and organizes recruitment of MKS-1, TMEM-231 (JBTS20), and TMEM237 (JBTS14), and in C. elegans functions redundantly with NPHP-4 to maintain cilium integrity, TZ docking, and assembly of membrane-to-microtubule Y-link connectors (PMID:26595381). Loss of TMEM107 reduces ciliated cell numbers and disrupts normal localization of ciliary proteins (PMID:26123494, PMID:26518474), can drive constitutive deciliation at the TZ (PMID:32163404), and places TMEM107 upstream of Smoothened, where its absence causes ectopic activation of the Sonic Hedgehog (SHH) pathway (PMID:37863656). In mice, Tmem107 acts genetically with Gli2 and Gli3 to pattern neuronal cell types and digit number, with hypomorphic schlei alleles retaining partial Gli activator/repressor function, and its loss elevates Shh/Gli1 activity and produces craniofacial and laterality defects reflecting cilium-dependent developmental signaling (PMID:22698544, PMID:28954202, PMID:31887266). In humans, TMEM107 mutation causes Meckel-Gruber syndrome (MKS13) through a ciliogenesis defect with perturbed SHH signaling (PMID:26123494). TMEM107 expression is itself controlled at the RNA-processing level by the minor (U12) spliceosome via SCNM1 (PMID:36084634).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2012 High

    Established that Tmem107 is required for cilia formation and functions within the Shh pathway to control vertebrate patterning, distinguishing it from complete cilia-loss mutants by its partial retention of Gli function.

    Evidence ENU forward genetics in mouse (schlei allele), genetic epistasis with Gli2/Gli3, in situ hybridization for Shh targets

    PMID:22698544

    Open questions at the time
    • Did not define molecular localization of TMEM107 within the cilium
    • Did not identify direct protein partners
  2. 2015 High

    Defined TMEM107's molecular role at the transition zone as an intermediate-layer organizer of the MKS module that recruits other ciliopathy proteins, explaining how it maintains cilium integrity.

    Evidence C. elegans genetic epistasis (nphp-4 double mutants) and super-resolution microscopy of TZ protein localization in worms and mammalian cells

    PMID:26595381

    Open questions at the time
    • Direct biochemical interaction with MKS-1/TMEM-231/JBTS-14 not resolved at residue level
    • Mechanism of redundancy with NPHP-4 not fully defined
  3. 2015 Medium

    Connected TMEM107 to human disease by showing mutation causes a ciliogenesis defect with perturbed Shh signaling and underlies Meckel-Gruber syndrome (MKS13).

    Evidence Patient fibroblast ciliogenesis and Shh assays, RT-PCR confirming aberrant splicing and NMD of a homozygous splicing variant

    PMID:26123494

    Open questions at the time
    • Single-lab patient cohort
    • Genotype-phenotype range across ciliopathies not delineated
  4. 2015 Medium

    Showed TMEM107 is required for correct ciliary protein composition, demonstrating its loss mislocalizes ciliary proteins across mouse and human systems.

    Evidence Immunofluorescence of ciliary protein localization in Tmem107 mouse mutant cells and an OFD patient fibroblast

    PMID:26518474

    Open questions at the time
    • Which specific proteins depend on TMEM107 not comprehensively cataloged
    • Mechanism of selective gating not resolved
  5. 2017 Medium

    Linked TMEM107 loss to specific developmental phenotypes and confirmed upregulated Shh activity, tying ciliary dysfunction to craniofacial morphogenesis.

    Evidence Tmem107-/- mouse histology, BrdU proliferation, immunofluorescence, and in situ hybridization for Shh/Gli1

    PMID:28954202

    Open questions at the time
    • Cell-type-specific basis of region-specific ciliary changes unclear
    • Direct link between altered IFT88/acetylated tubulin and TMEM107 loss not mechanistically dissected
  6. 2019 Medium

    Used graded Tmem107 alleles to separate cilium-dependent from Shh-dependent requirements in left-right patterning, showing midline barrier formation needs cilia but not necessarily Shh.

    Evidence Comparison of Tmem107-null vs. hypomorphic schlei mice with in situ hybridization for Lefty1/Shh genes and L-R organ analysis

    PMID:31887266

    Open questions at the time
    • Molecular basis of allelic dose-dependence on cilia number not defined
    • Single-lab study
  7. 2020 Medium

    Established that TMEM107 controls ciliary shedding at the transition zone, with loss inducing constitutive deciliation, in an evolutionarily conserved ciliate model.

    Evidence RNAi depletion in Paramecium with live imaging of deciliation and super-resolution/EM localization showing 9-fold TZ symmetry

    PMID:32163404

    Open questions at the time
    • Molecular trigger of deciliation downstream of TMEM107 loss unknown
    • Conservation of the shedding role in mammals not directly tested
  8. 2020 Low

    Indicated that TMEM107 assembles tissue-specific protein complexes relevant to ciliary function.

    Evidence Tagged TMEM107 pull-down from HEK293T lysate against porcine retina lysate followed by mass spectrometry

    PMID:32853754

    Open questions at the time
    • Single pulldown/MS without reciprocal validation
    • Specific tissue-specific partners not functionally confirmed
    • No follow-up on functional consequence of identified interactions
  9. 2022 Medium

    Revealed that TMEM107 expression is governed at the RNA-processing level by the minor spliceosome, connecting U12 splicing to ciliary length control.

    Evidence Transcriptomics of SCNM1-deficient fibroblasts, CRISPR KO, siRNA, and retroviral SCNM1 rescue with cilia length measurement

    PMID:36084634

    Open questions at the time
    • Whether minor-intron mis-splicing of TMEM107 contributes to specific disease phenotypes not established
    • Other minor-spliceosome targets affecting cilia not separated
  10. 2023 Medium

    Placed TMEM107 upstream of Smoothened/SHH activation at the cilium and demonstrated its loss causes ectopic SHH activation and retinal defects in human cell and organoid models.

    Evidence CRISPR TMEM107 knockout in ARPE-19 cells and retinal organoids, Smoothened agonist treatment, immunofluorescence and RT-qPCR

    PMID:37863656

    Open questions at the time
    • Direct molecular link between TZ gating and Smoothened regulation not resolved
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TMEM107 biochemically gates the transition zone barrier and mechanistically restrains Smoothened/SHH activation remains undefined.
  • No structural model of TMEM107 within the MKS module
  • Direct binding interfaces with MKS-1/TMEM-231/TMEM237 not mapped
  • Mechanism coupling diffusion barrier integrity to Smoothened control unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1
Localization
GO:0005929 cilium 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
MKS1NPHP4TMEM231TMEM237
Complex memberships
MKS module / transition zone

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 TMEM107 localizes to the transition zone (TZ) of cilia and occupies an intermediate layer of the TZ-localized MKS module, where it organizes recruitment of ciliopathy proteins MKS-1, TMEM-231 (JBTS20), and JBTS-14 (TMEM237). In C. elegans, TMEM-107 functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking, and assembly of membrane-to-microtubule Y-link connectors. Super-resolution microscopy revealed periodic localizations of MKS module membrane proteins within the TZ in both worms and mammalian cells. Genetic epistasis in C. elegans (double mutants with nphp-4), super-resolution microscopy, fluorescence imaging of TZ localization and protein recruitment Nature cell biology High 26595381
2012 Mouse Tmem107 (schlei mutant) is required for normal cilia formation and acts genetically in the Sonic hedgehog (Shh) signaling pathway; Tmem107 acts in combination with Gli2 and Gli3 to pattern ventral and intermediate neuronal cell types and determines digit number by regulating a subset of Shh target genes. Schlei mutants retain partial Gli activator and repressor function, unlike complete cilia-loss mutants. Forward genetics (ENU screen), mouse knockout/hypomorphic allele analysis, genetic epistasis with Gli2/Gli3, in situ hybridization for Shh pathway targets Developmental biology High 22698544
2015 TMEM107 mutation in human patients causes a ciliogenesis defect with accompanying perturbation of Sonic hedgehog (Shh) signaling, as demonstrated in patient fibroblasts. Loss of TMEM107 leads to marked reduction in ciliated cells and is the cause of MKS13 (Meckel-Gruber syndrome locus 13); aberrant splicing and nonsense-mediated decay confirmed as the molecular mechanism for a homozygous splicing variant. Patient fibroblast analysis (ciliogenesis assay), RT-PCR for aberrant splicing/NMD, Shh signaling assay in patient cells Human molecular genetics Medium 26123494
2015 TMEM107 functions within cilia to regulate ciliary protein composition; key ciliary proteins fail to localize normally in cilia derived from Tmem107 mouse mutants and from a human OFD patient with TMEM107 mutation. Immunofluorescence of ciliary protein localization in mouse mutant cells and human patient fibroblasts Human mutation Medium 26518474
2017 Tmem107-/- mice exhibit craniofacial defects including cleft lip, cleft palate, exencephaly, and microphthalmia/anophthalmia. Palatal defects arise from increased mesenchymal proliferation and defective horizontalization of palatal shelves. Region-specific changes in ciliary morphology occur with altered acetylated tubulin and IFT88 expression. Shh and Gli1 expression is increased in Tmem107-/- animals, confirming upregulated Shh pathway activity upon TMEM107 loss. Mouse knockout (Tmem107-/-), histology, immunofluorescence, in situ hybridization for Shh/Gli1, BrdU proliferation assay Journal of dental research Medium 28954202
2020 Depletion of TMEM107 (along with TMEM216/MKS2) in Paramecium induces constitutive deciliation of some cilia, establishing that TMEM107 controls ciliary shedding at the transition zone. All five TZ proteins studied (TMEM107, TMEM216, CEP290, RPGRIP1L, NPHP4) localize to the TZ with 9-fold symmetry at the most distal part of the TZ in growing cilia. RNAi depletion in Paramecium, live imaging of deciliation, super-resolution/electron microscopy of TZ localization PLoS biology Medium 32163404
2019 Near-complete loss of cilia in Tmem107-null mice leads to left pulmonary isomerism due to failure of the midline barrier, while hypomorphic Tmem107schlei mutants with partially retained cilia can establish and maintain left-right asymmetry. Lefty1 expression and midline barrier formation require cilia but not necessarily Shh signaling, as revealed by comparing the two Tmem107 alleles. Mouse knockout and hypomorphic allele comparison, in situ hybridization for Lefty1 and Shh pathway genes, morphological analysis of L-R organ asymmetry Developmental biology Medium 31887266
2023 TMEM107 deficiency in retinal organoids results in loss of primary cilia, down-regulation of retina-specific genes, and cyst formation. Knockout of TMEM107 in human ARPE-19 cells prevents primary cilia formation and impairs response to Smoothened agonist treatment due to ectopic activation of the SHH pathway, placing TMEM107 upstream of Smoothened/SHH pathway activation at the cilium. TMEM107 knockout in human ARPE-19 cells, retinal organoid culture, Smoothened agonist treatment, immunofluorescence for primary cilia, RT-qPCR for retinal genes Life science alliance Medium 37863656
2022 TMEM107 expression is severely reduced in SCNM1-deficient cells due to defective minor intron (U12) splicing. Loss of TMEM107 expression contributes to abnormally elongated cilia in SCNM1-deficient fibroblasts; reintroduction of SCNM1 restores cilia length and TMEM107 expression, demonstrating that TMEM107 is regulated at the RNA processing level by the minor spliceosome. Transcriptome analysis of patient fibroblasts vs. controls, CRISPR-Cas9 SCNM1 knockout, siRNA knockdown, retroviral SCNM1 rescue, cilia length measurement American journal of human genetics Medium 36084634
2020 TMEM107 forms tissue-specific protein complexes identifiable by pull-down from porcine retina tissue, demonstrating that its interaction partners vary in a tissue-specific manner relevant to ciliary function. Tagged TMEM107 pull-down from human HEK293T cell lysates used as bait against porcine retina tissue lysates, followed by mass spectrometry Journal of proteomics Low 32853754

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome. Nature cell biology 108 26595381
2017 Fifteen years of research on oral-facial-digital syndromes: from 1 to 16 causal genes. Journal of medical genetics 87 28289185
2012 Forward genetics uncovers Transmembrane protein 107 as a novel factor required for ciliogenesis and Sonic hedgehog signaling. Developmental biology 39 22698544
2015 Identification of a novel MKS locus defined by TMEM107 mutation. Human molecular genetics 38 26123494
2021 EGR1 dysregulation defines an inflammatory and leukemic program in cell trajectory of human-aged hematopoietic stem cells (HSC). Stem cell research & therapy 33 34294125
2020 MKS-NPHP module proteins control ciliary shedding at the transition zone. PLoS biology 31 32163404
2014 Detection of coding microsatellite frameshift mutations in DNA mismatch repair-deficient mouse intestinal tumors. Molecular carcinogenesis 31 25213383
2017 Ciliopathy Protein Tmem107 Plays Multiple Roles in Craniofacial Development. Journal of dental research 26 28954202
2007 Aberrant splicing is a common mutational mechanism in MKS1, a key player in Meckel-Gruber syndrome. Human mutation 21 17437276
2015 TMEM107 Is a Critical Regulator of Ciliary Protein Composition and Is Mutated in Orofaciodigital Syndrome. Human mutation 19 26518474
2020 TMEM107 inhibits EMT and invasion of NSCLC through regulating the Hedgehog pathway. Thoracic cancer 17 33124203
2022 Mutations in SCNM1 cause orofaciodigital syndrome due to minor intron splicing defects affecting primary cilia. American journal of human genetics 14 36084634
2020 Tissue- and isoform-specific protein complex analysis with natively processed bait proteins. Journal of proteomics 11 32853754
2023 Role of ciliopathy protein TMEM107 in eye development: insights from a mouse model and retinal organoid. Life science alliance 8 37863656
2019 Loss of ciliary transition zone protein TMEM107 leads to heterotaxy in mice. Developmental biology 8 31887266
2023 Differential alternative splicing analysis links variation in ZRSR2 to a novel type of oral-facial-digital syndrome. Genetics in medicine : official journal of the American College of Medical Genetics 3 38158857
2023 A gene-based association test of interactions for maternal-fetal genotypes identifies genes associated with nonsyndromic congenital heart defects. Genetic epidemiology 2 37341229
2025 Identifying the anti-infection NK and T cell subgroups in preterm newborns with sepsis using single-cell RNA-seq analysis. European journal of medical research 1 41152979
2025 RETRACTION: TMEM107 Inhibits EMT and Invasion of NSCLC Through Regulating the Hedgehog Pathway. Thoracic cancer 0 40051292
2025 Establishment of a highly sensitive porcine alveolar macrophage cell line for African swine fever virus. In vitro cellular & developmental biology. Animal 0 40266442
2025 Expanding the phenotype associated with biallelic SCNM1 variants. Human genomics 0 41291844
2025 Molecular Spectrum and Deep Phenotyping of a Turkish Joubert Syndrome Cohort, Including a Potential Candidate Gene, NPHP4. Turkish archives of pediatrics 0 42044428

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