TOPORS

Chr 9AD

TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase

Also known as: LUN, P53BP3, RP31, TP53BPL

NCBI Gene: 10210 ENSG00000197579 UniProt: Q9NS56 OMIM: 609507

This gene encodes an E3 ubiquitin ligase that regulates protein stability and chromatin modification, with high expression in testis and functions in cell growth regulation and DNA damage response. Mutations cause retinitis pigmentosa 31, an inherited retinal dystrophy, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.242), indicating intolerance to protein-disrupting mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a nuclear protein which is serine and arginine rich, and contains a RING-type zinc finger domain. It is highly expressed in the testis, and functions as an ubiquitin-protein E3 ligase. Mutations in this gene are associated with retinitis pigmentosa type 31. Alternatively spliced transcript variants, encoding different isoforms, have been observed for this locus. [provided by RefSeq, Sep 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Retinitis pigmentosa 31MIM #609923

Clinical highlights

Gene-disease validity (ClinGen)

TOPORS-related retinopathy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.24

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — TOPORS