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TMEM237
transmembrane protein 237
TMEM237 is located on the long (q) arm of chromosome 2, at band 2q33.1. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
TMEM237 encodes a transmembrane protein that localises to primary cilia, cellular structures critical for developmental signalling and sensory processes. Primary cilia act as cellular antennae, detecting external signals and coordinating responses during embryonic development and tissue maintenance. The protein encoded by TMEM237 participates in the assembly and maintenance of these organelles.
Pathogenic variants in TMEM237 typically follow an autosomal recessive inheritance pattern, meaning an affected individual inherits altered copies from both parents. Loss of functional TMEM237 protein disrupts cilia formation or stability, resulting in clinical features characteristic of ciliopathies. These conditions may affect the brain, eyes, kidneys, and other organs that depend on normal cilia function during development.
What the gene does
The TMEM237 protein localises to the transition zone of primary cilia, a specialised region that controls which molecules enter and exit the ciliary compartment. This gatekeeper function ensures proper composition of the ciliary membrane and internal structure. The transition zone serves as a diffusion barrier, preventing inappropriate proteins from entering the cilium whilst permitting selective transport of signalling components.
TMEM237 contributes to the structural integrity of the ciliary transition zone through interactions with other ciliopathy-associated proteins. By maintaining this boundary, the protein helps establish the distinct biochemical environment necessary for cilia-based signalling pathways. These pathways regulate embryonic patterning, neural tube formation, retinal development, and kidney morphogenesis. Disruption of transition zone organisation impairs multiple ciliary signalling cascades, including Hedgehog and planar cell polarity pathways, which coordinate tissue development across organ systems.
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Chromosome location
TMEM237 resides on chromosome 2 at position q33.1, within the long arm of the chromosome. This genomic region contains multiple genes involved in developmental processes. The specific chromosomal location places TMEM237 in a gene-dense area subject to various regulatory influences during embryonic development.
Protein structure
The TMEM237 protein comprises 408 amino acids and contains predicted transmembrane domains characteristic of membrane-associated proteins. A substantial disordered region spans amino acids 1 through 137 at the N-terminus. Intrinsically disordered regions often mediate protein-protein interactions and provide flexibility for dynamic assembly processes. This extended disordered segment may facilitate interactions with other transition zone components, allowing TMEM237 to participate in the multi-protein complexes that constitute the ciliary gate. The transmembrane segments anchor the protein within ciliary membranes, positioning the disordered domains for functional interactions.
Key variants
Pathogenic variants in TMEM237 generally result in loss of protein function through mechanisms including premature termination, frameshift mutations, or missense changes that disrupt protein stability. Most disease-causing variants follow autosomal recessive inheritance, requiring biallelic pathogenic changes for clinical manifestation. The variant spectrum includes nonsense mutations, small deletions or insertions causing frameshifts, and splice-site alterations that prevent normal protein production.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
TMEM237-related ciliopathies predominantly present as Joubert syndrome, a neurodevelopmental disorder characterised by a distinctive hindbrain malformation called the molar tooth sign. Affected individuals may exhibit intellectual disability, breathing abnormalities in infancy, and coordination difficulties. Some individuals develop retinal dystrophy leading to vision impairment, whilst renal involvement occurs in a subset of cases. The phenotypic spectrum reflects the broad developmental role of primary cilia, with clinical severity and specific organ involvement varying among affected individuals. Features may overlap with other ciliopathy syndromes, reflecting shared underlying cellular mechanisms.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic TMEM237 variants typically follow autosomal recessive or autosomal dominant inheritance.
Carrier frequency by population How common is heterozygous TMEM237 carrier status across ancestry groups?UK clinical status
TMEM237 holds green classification status across multiple NHS England Genomic Medicine Service PanelApp panels, indicating strong evidence for its role in inherited conditions. The gene appears on panels for neurological ciliopathies, ophthalmological ciliopathies, renal ciliopathies, and rare multisystem ciliopathy disorders, reflecting the diverse organ systems affected by TMEM237 variants. Additional memberships include the DDG2P panel for developmental disorders, as well as intellectual disability (R29), retinal disorders (R32), and structural eye disease (R36) panels. This comprehensive panel representation supports inclusion of TMEM237 in NHS diagnostic testing pathways for individuals presenting with features consistent with ciliopathies.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What inheritance pattern does TMEM237 follow?
TMEM237-related conditions typically follow autosomal recessive inheritance, meaning an affected individual inherits one pathogenic variant from each parent. Carriers with one altered copy generally do not show symptoms.
Which organs are most commonly affected by TMEM237 variants?
TMEM237 variants primarily affect the brain, leading to characteristic hindbrain malformation and neurodevelopmental features. The eyes and kidneys may also be involved, reflecting the widespread importance of cilia during development.
Is genetic testing for TMEM237 available through the NHS?
Yes, TMEM237 testing is available through NHS Genomic Medicine Service pathways for individuals presenting with clinical features consistent with ciliopathies, including Joubert syndrome and related disorders.