TOPORS

Chr 9AD

TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase

Also known as: LUN, P53BP3, RP31, TP53BPL

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.241 OMIM phenotype
Clinical SummaryTOPORS
🧬
Gene-Disease Validity (ClinGen)
TOPORS-related retinopathy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.999
Z-score 5.09
OE 0.11 (0.050.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.05Z-score
OE missense 0.87 (0.810.94)
486 obs / 555.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.050.24)
00.351.4
Missense OE0.87 (0.810.94)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 4 / 37.8Missense obs/exp: 486 / 555.7Syn Z: -1.21
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTOPORS-related retinitis pigmentosaLOFAD
DN
0.3097th %ile
GOF
0.3193th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TOPORS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Always at the Top.
Heidelbaugh JJ·Prim Care
2024
Being on top.
Saunders P·Glob Public Health
2022
Top Reads.
·J Immunol
2023
Top Reads.
·J Immunol
2024
Top 5 full-text resultsSearch PubTator3 ↗