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TECPR2
tectonin beta-propeller repeat containing 2
TECPR2 is located on the long (q) arm of chromosome 14, at band 14q32.33. Arm ratio per GRCh38 - banding schematic.
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Overview
TECPR2 (tectonin beta-propeller repeat containing 2) resides on chromosome 14 and encodes a protein involved in autophagy, the cellular housekeeping mechanism that removes damaged or unnecessary components. This protein is particularly important in nerve cells, where efficient autophagy helps maintain cellular health over a person's lifetime. When TECPR2 function is compromised through pathogenic variants, the resulting disruption to autophagy can lead to progressive neurological features including muscle stiffness, intellectual disability, and difficulties with autonomic functions such as digestion and breathing.
Inherited changes in TECPR2 are recognised across multiple NHS clinical pathways for neurological conditions. The gene is included in panels for hereditary spastic paraplegia, ataxia, intellectual disability, and neuropathy, reflecting the diverse neurological presentations associated with TECPR2 dysfunction.
What the gene does
The TECPR2 protein facilitates autophagy by supporting the formation of autophagosomes, the double-membrane compartments that isolate cellular materials destined for degradation. Research suggests this protein acts during the early stages of autophagosome assembly, helping to coordinate the machinery that packages worn-out organelles, misfolded proteins, and other cellular debris for transport to lysosomes where they are broken down.
Within nerve cells, autophagy serves a particularly vital role because neurons are long-lived and must continuously clear accumulated cellular waste to prevent toxicity. The TECPR2 protein appears to be especially important for maintaining this clearance system in the nervous system. Evidence suggests that when TECPR2 function is impaired, autophagic flux becomes inefficient, leading to the accumulation of cellular debris that can interfere with neuronal signalling and survival.
The protein's structural features enable it to interact with other components of the autophagy machinery, though the precise molecular partnerships and signalling pathways remain areas of active investigation.
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Chromosome location
TECPR2 is located on the long arm of chromosome 14 at position 32.33 (14q32.33). This chromosomal region contains numerous genes, and TECPR2 spans a genomic segment that encodes a protein of 1,411 amino acids. The gene's location near the telomeric end of chromosome 14 places it in a region associated with several neurological and developmental genes.
Protein structure
The TECPR2 protein comprises 1,411 amino acids organised into several distinct structural regions. The amino-terminal portion contains seven WD repeats spanning positions 23 through 343 (WD 1 through WD 7), which typically form a propeller-like structure that mediates protein-protein interactions. These repeats are followed by multiple disordered regions at positions 379-439, 463-542, 579-637, and 758-779, which may provide flexibility for interactions with different cellular partners.
The carboxy-terminal half features six TECPR repeats (TECPR 1 through TECPR 6) spanning positions 945 through 1353. These specialised repeats are thought to be important for the protein's role in autophagy, potentially mediating interactions with autophagosomal membranes or other components of the cellular recycling machinery. A final disordered region occupies positions 1388-1411 at the extreme carboxy terminus. The combination of WD repeats and TECPR repeats suggests the protein serves as a scaffold, bringing together different elements required for autophagosome formation.
Key variants
Several pathogenic variants in TECPR2 have been reported in individuals with spastic paraplegia type 49. These variants typically result in reduced or absent protein function, compromising the autophagy process. The spectrum of variants includes loss-of-function changes that prevent normal protein production or stability, though the full landscape of pathogenic variation continues to be characterised as more families are studied.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Changes in TECPR2 are associated with spastic paraplegia type 49, a progressive neurological condition characterised by increasing muscle stiffness and weakness in the lower limbs. Affected individuals typically develop intellectual disability and may experience a range of other neurological difficulties. The severity and specific features can vary between individuals, though progressive spasticity and cognitive impairment are consistent findings. The condition reflects the critical importance of efficient autophagy for maintaining neuronal health throughout life.
No disease links recorded for this gene in our reference set.
UK clinical status
TECPR2 appears on several NHS Genomic Medicine Service gene panels, reflecting its clinical relevance across multiple neurological presentations. The gene holds green classification status on the Childhood onset hereditary spastic paraplegia panel (R61), the Intellectual disability panel (R29), and the Hereditary neuropathy or pain disorder panel (R78). It is also included in the Ataxia and cerebellar anomalies narrow panel and the Developmental Disorders Genotype to Phenotype (DDG2P) resource. This multi-panel presence indicates that TECPR2 variants should be considered in the differential diagnosis of children and young people presenting with progressive spasticity, developmental delay, or complex neurological features.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is autophagy and why does it matter for nerve cells?
Autophagy is the cellular process that breaks down and recycles damaged or unnecessary components. In nerve cells, which must function throughout a person's lifetime, autophagy is essential for clearing accumulated cellular debris that could otherwise interfere with neuronal signalling and survival.
What does green status on an NHS panel mean?
Green classification on an NHS Genomic Medicine Service panel indicates that there is strong evidence supporting the gene's role in the specified condition. For TECPR2, green status across multiple panels reflects well-established clinical validity for testing in individuals with hereditary spastic paraplegia, intellectual disability, and related neurological presentations.