TTC5

Chr 14q11.2

tetratricopeptide repeat domain 5

Aliases:: Strap
MANE:: ENST00000258821.8

OMIM: 619014 ↗NCBI: 91875 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

TTC5 · Q8N0Z6

v62025-08-01

Predicted Aligned Error matrix for TTC5 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

93.4/ 100

Very high

440 residues

Confidence breakdown

Very high(≥ 90)84%
Confident(70–90)13%
Low(50–70)2%
Very low(< 50)2%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Severe microcephaly
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism
0.74
neurodevelopmental disorder
0.37
autosomal recessive non-syndromic intellectual disability
0.37
Neurodevelopmental delay
0.12
autosomal recessive spondylocostal dysostosis
0.08
acute myeloid leukemia
0.07
spondylolisthesis
0.07
Scheuermann disease
0.06
Familial Scheuermann disease
0.06
X-linked osteoporosis with fractures
0.06

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Tetratricopeptide repeat protein 5

Cofactor involved in the regulation of various cellular mechanisms such as actin regulation, autophagy, chromatin regulation and DNA repair (PubMed:18451878, PubMed:31727855). In non-stress conditions, interacts with cofactor JMY in the cytoplasm which prevents JMY's actin nucleation activity and ability to activate the Arp2/3 complex. Acts as a negative regulator of nutrient stress-induced autophagy by preventing JMY's interaction with MAP1LC3B, thereby preventing autophagosome formation (By similarity). Involves in tubulin autoregulation by promoting its degradation in response to excess soluble tubulin (PubMed:31727855). To do so, associates with the active ribosome near the ribosome exit tunnel and with nascent tubulin polypeptides early during their translation, triggering tubulin mRNA-targeted degradation (PubMed:31727855). Following DNA damage, phosphorylated by DNA damage responsive protein kinases ATM and CHEK2, leading to its nuclear accumulation and stability. Nuclear TTC5/STRAP promotes the assembly of a stress-responsive p53/TP53 coactivator complex, which includes the coactivators JMY and p300, thereby increasing p53/TP53-dependent transcription and apoptosis. Also recruits arginine methyltransferase PRMT5 to p53/TP53 when DNA is damaged, allowing PRMT5 to methylate p53/TP53. In DNA stress conditions, also prevents p53/TP53 degradation by E3 ubiquitin ligase MDM2 (By similarity). Upon heat-shock stress, forms a chromatin-associated complex with heat-shock factor 1 HSF1 and p300/EP300 to stimulate heat-shock-responsive transcription, thereby increasing cell survival (PubMed:18451878). Mitochondrial TTC5/STRAP interacts with ATP synthase subunit beta ATP5F1B which decreased ATP synthase activity and lowers mitochondrial ATP production, thereby regulating cellular respiration and mitochondrial-dependent apoptosis. Mitochondrial TTC5/STRAP also regulates p53/TP53-mediated apoptosis (By similarity)