FRRS1L

Chr 9AR

ferric chelate reductase 1 like

Also known as: C9orf4, CG-6, CG6, DEE37, EIEE37

The protein is a component of the outer core of AMPA receptors in the brain that modulates glutamate signaling. Biallelic mutations cause developmental and epileptic encephalopathy 37, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disrupted glutamate receptor function leading to abnormal neuronal excitability and seizures.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.091 OMIM phenotype
Clinical SummaryFRRS1L
🧬
Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.09LOEUF
pLI 0.001
Z-score 1.37
OE 0.55 (0.301.09)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.58Z-score
OE missense 0.86 (0.741.00)
121 obs / 140.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.55 (0.301.09)
00.351.4
Missense OE0.86 (0.741.00)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 6 / 10.9Missense obs/exp: 121 / 140.4Syn Z: -0.03
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongFRRS1L-related epileptic encephalopathy with continuous spike-and-wave during sleepLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6649th %ile
GOF
0.4875th %ile
LOF
0.3164th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FRRS1L · 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
Open Research Assistant →