GRSF1

Chr 4

G-rich RNA sequence binding factor 1

GRSF1 encodes a regulator of post-transcriptional mitochondrial gene expression that binds G-rich RNA elements and is required for mitochondrial ribosome assembly and recruitment of mitochondrial mRNAs and long non-coding RNAs. Mutations cause mitochondrial neurodegeneration, cataracts, and hearing loss with infantile onset, following autosomal recessive inheritance. The gene shows no constraint against loss-of-function variants (pLI near zero), consistent with recessive disease causation.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.23
Clinical SummaryGRSF1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 78 VUS of 131 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.23LOEUF
pLI 0.000
Z-score 0.71
OE 0.84 (0.581.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.51Z-score
OE missense 1.10 (0.991.22)
245 obs / 223.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.84 (0.581.23)
00.351.4
Missense OE1.10 (0.991.22)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 19 / 22.6Missense obs/exp: 245 / 223.5Syn Z: -0.03

ClinVar Variant Classifications

131 submitted variants in ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS78
Likely Benign6
Benign2
21
Pathogenic
1
Likely Pathogenic
78
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
68
10
0
78
Likely Benign
0
3
1
2
6
Benign
0
0
1
1
2
Total071343108

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

View in ClinVar →

Protein Context — Lollipop Plot

GRSF1 · 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.

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Clinical Literature
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