GRSF1

Chr 4

G-rich RNA sequence binding factor 1

NCBI Gene: 2926 ENSG00000132463 UniProt: Q12849 OMIM: 604851

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a cellular protein that binds RNAs containing the G-rich element. The protein is localized in the cytoplasm, and has been shown to stimulate translation of viral mRNAs in vitro. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 1.23

Clinical Summary— GRSF1

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Population Constraint (gnomAD)

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

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ClinVar Variants

68 VUS of 99 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.000

Z-score 0.71

OE 0.84 (0.58–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.51Z-score

OE missense 1.10 (0.99–1.22)

245 obs / 223.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.84 (0.58–1.23)

0≤0.351.4

Missense OE?1.10 (0.99–1.22)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 19 / 22.6Missense obs/exp: 245 / 223.5Syn Z: -0.03

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

VUS68

Likely Benign6

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	68	0	0	68
Likely Benign	3	1	2	6
Benign	0	1	1	2
Total	71	2	3	76

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap GRSF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →