RASD1

Chr 17

ras related dexamethasone induced 1

Also known as: AGS1, DEXRAS1, MGC:26290

NCBI Gene: 51655 ENSG00000108551 UniProt: Q9Y272 OMIM: 605550

The RASD1 protein is a small GTPase that activates G-protein signaling and acts as a nucleotide exchange factor for Gi-Go proteins. Mutations in RASD1 cause neurodevelopmental disorders with intellectual disability, typically presenting in early childhood. The gene follows an autosomal dominant inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the Ras superfamily of small GTPases and is induced by dexamethasone. The encoded protein is an activator of G-protein signaling and acts as a direct nucleotide exchange factor for Gi-Go proteins. This protein interacts with the neuronal nitric oxide adaptor protein CAPON, and a nuclear adaptor protein FE65, which interacts with the Alzheimer's disease amyloid precursor protein. This gene may play a role in dexamethasone-induced alterations in cell morphology, growth and cell-extracellular matrix interactions. Epigenetic inactivation of this gene is closely correlated with resistance to dexamethasone in multiple myeloma cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2011]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.18

Clinical Summary— RASD1

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.039

Z-score 1.28

OE 0.46 (0.21–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.37Z-score

OE missense 0.92 (0.81–1.05)

160 obs / 173.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.21–1.18)

0≤0.351.4

Missense OE?0.92 (0.81–1.05)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 3 / 6.5Missense obs/exp: 160 / 173.9Syn Z: 0.28

This gene — mechanism propensity

0.80top 25%

GOF

0.79top 25%

LOF

0.3162th %ile

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

DNprediction above median

GOFprediction 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.