RIMKLA

Chr 1

ribosomal modification protein rimK like family member A

Also known as: FAM80A, NAAGS, NAAGS-II, NAAGS2

NCBI Gene: 284716ENSG00000177181UniProt: Q8IXN7OMIM: 618949

This enzyme catalyzes the synthesis of N-acetyl-L-aspartyl-L-glutamate (NAAG) and related compounds in the cytoplasm. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by seizures, developmental delays, and progressive neurological deterioration. The gene shows minimal constraint against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.01
Clinical Summary— RIMKLA
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 37 VUS of 52 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.001
Z-score 1.53
OE 0.54 (0.31–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.22Z-score
OE missense 0.76 (0.67–0.87)
160 obs / 209.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.31–1.01)
0≤0.351.4
Missense OE0.76 (0.67–0.87)
0≤0.61.4
Synonymous OE0.77
0≤1.21.6
LoF obs/exp: 7 / 12.9Missense obs/exp: 160 / 209.7Syn Z: 1.63
DN
0.6842th %ile
GOF
0.6833th %ile
LOF
0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

52 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic2
VUS37
7
Pathogenic
2
Likely Pathogenic
37
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
2
0
2
VUS
0
35
2
0
37
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total03511046

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

View in ClinVar →

Protein Context — Lollipop Plot

RIMKLA · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis
Yan H et al.·Signal Transduct Target Ther
2024
NAAG synthetase deficiency has only low influence on pathogenesis in a Canavan disease mouse model.
Becker I et al.·J Inherit Metab Dis
2023Functional
Targeting Hypoxia and HIF1alpha in Triple-Negative Breast Cancer: New Insights from Gene Expression Profiling and Implications for Therapy.
Han D et al.·Biology (Basel)
2024
Comprehensive bioinformatics analysis identified and validated KIT as a key gene associated with glutamine metabolism in thyroid carcinoma.
Li X et al.·Medicine (Baltimore)
2025
A novel diabetic foot ulcer diagnostic model: identification and analysis of genes related to glutamine metabolism and immune infiltration
Shi H et al.·BMC Genomics
2024Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients