LONRF1

Chr 8

LON peptidase N-terminal domain and ring finger 1

Also known as: RNF191

LONRF1 encodes a protein predicted to bind zinc ions and localize to the cytosol. Mutations cause autosomal recessive neurodevelopmental disorder with epilepsy, spasticity, and brain abnormalities. The gene shows significant constraint against loss-of-function variants (LOEUF 0.39), suggesting intolerance to protein-disrupting mutations.

Summary from RefSeq
Research Assistant →
0
Active trials
1
Pubs (1 yr)
88
P/LP submissions
0%
P/LP missense
0.39
LOEUF
Mechanism
Clinical SummaryLONRF1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
88 unique Pathogenic / Likely Pathogenic· 117 VUS of 228 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.612
Z-score 4.26
OE 0.21 (0.120.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.37Z-score
OE missense 0.94 (0.861.03)
303 obs / 321.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.120.39)
00.351.4
Missense OE0.94 (0.861.03)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 7 / 33.6Missense obs/exp: 303 / 321.9Syn Z: -1.70

ClinVar Variant Classifications

228 submitted variants in ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic5
VUS117
Likely Benign10
Benign1
83
Pathogenic
5
Likely Pathogenic
117
VUS
10
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
83
0
83
Likely Pathogenic
0
0
5
0
5
VUS
0
109
8
0
117
Likely Benign
0
6
3
1
10
Benign
0
0
1
0
1
Total01151001216

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LONRF1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC