RASGRF1

Chr 15

Ras protein specific guanine nucleotide releasing factor 1

Also known as: CDC25, CDC25L, GNRP, GRF1, GRF55, H-GRF55, PP13187, ras-GRF1

NCBI Gene: 5923 ENSG00000058335 UniProt: Q13972

The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) similar to the Saccharomyces cerevisiae CDC25 gene product. Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The studies of the similar gene in mouse suggested that the Ras-GEF activity of this protein in brain can be activated by Ca2+ influx, muscarinic receptors, and G protein beta-gamma subunit. Mouse studies also indicated that the Ras-GEF signaling pathway mediated by this protein may be important for long-term memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Mar 2009]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.21

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 6.58

OE 0.11 (0.06–0.21)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

4.21Z-score

OE missense 0.57 (0.53–0.62)

446 obs / 776.1 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.11 (0.06–0.21)

0≤0.351.4

Missense OE?0.57 (0.53–0.62)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 7 / 63.6Missense obs/exp: 446 / 776.1Syn Z: 0.82

Background carrier burden — how many people carry a rare variant somewhere in RASGRF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 72

1,199 rare PASS variants

Rare truncating (LoF)

1 in 1,600

99 rare PASS variants

Rare synonymous (reference)

1 in 74

654 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RASGRF1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 76	1 in 1,600
South Asian	~43k	1 in 51	1 in 8,500
Remaining (unassigned)	~30k	1 in 77	1 in 1,400
European (Finnish)	~27k	1 in 170	1 in 700
Admixed American	~22k	1 in 64	1 in 1,300
African / African American	~21k	1 in 70	1 in 3,500
East Asian	~20k	1 in 70	≈ 1 in 6,500
Ashkenazi Jewish	~13k	1 in 430	none seen
Middle Eastern	~2,884	1 in 69	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 27 coding exons well covered in gnomAD exomes and genomes.? see exons ↓