SETX

Chr 9q34.13

senataxin

Aliases:: KIAA0625, AOA2, Sen1, STEX
MANE:: ENST00000224140.6

OMIM: 608465 ↗NCBI: 23064 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

SETX · Q7Z333

v62025-08-01

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

Mean pLDDT

52.3/ 100

Low

2,677 residues

Confidence breakdown

Very high(≥ 90)11%
Confident(70–90)28%
Low(50–70)8%
Very low(< 50)54%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Adult onset neurodegenerative disorder
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Albinism or congenital nystagmus
BIALLELIC, autosomal or pseudoautosomal
Amyotrophic lateral sclerosis/motor neuron disease
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia
BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood
BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

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Disease associations (Open Targets)

spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
0.82
amyotrophic lateral sclerosis type 4
0.79
Spinocerebellar ataxia with axonal neuropathy type 2
0.67
hereditary disease
0.53
neurodegenerative disease
0.48
cerebellar ataxia
0.41
distal hereditary motor neuropathy
0.41
amyotrophic lateral sclerosis
0.38
frontotemporal dementia
0.36
spastic ataxia
0.35

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

Protein function (UniProt)

Helicase senataxin

ATP-dependent 5'-3' helicase that preferentially unwinds RNA:DNA substrates over DNA:DNA substrates, playing a crucial role in resolving 5'-overhang RNA:DNA hybrids (R-loops) and promoting transcription termination (PubMed:36864660). Plays a role in transcription regulation by its ability to modulate RNA Polymerase II (Pol II) binding to chromatin and through its interaction with proteins involved in transcription (PubMed:19515850, PubMed:21700224). Contributes to the mRNA splicing efficiency and splice site selection (PubMed:19515850). Required for the resolution of R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site, allowing XRN2 recruitment and XRN2-mediated degradation of the downstream cleaved RNA and hence efficient RNA polymerase II (RNAp II) transcription termination (PubMed:19515850, PubMed:21700224, PubMed:26700805). Required for the 3' transcriptional termination of PER1 and CRY2, thus playing an important role in the circadian rhythm regulation (By similarity). Involved in DNA double-strand breaks damage response generated by oxidative stress (PubMed:17562789). In association with RRP45, targets the RNA exosome complex to sites of transcription-induced DNA damage (PubMed:24105744). Plays a role in the development and maturation of germ cells: essential for male meiosis, acting at the interface of transcription and meiotic recombination, and in the process of gene silencing during meiotic sex chromosome inactivation (MSCI) (By similarity). May be involved in telomeric stability through the regulation of telomere repeat-containing RNA (TERRA) transcription (PubMed:21112256). Plays a role in neurite outgrowth in hippocampal cells through FGF8-activated signaling pathways. Inhibits retinoic acid-induced apoptosis (PubMed:21576111)