DRG2

Chr 17

developmentally regulated GTP binding protein 2

NCBI Gene: 1819 ENSG00000108591 UniProt: P55039 OMIM: 602986

DRG2 encodes a GTP-binding protein that catalyzes the conversion of GTP to GDP and may play a role in translation when modified. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly and progressive brain atrophy, typically presenting in infancy with seizures, developmental delays, and neurodegeneration.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a GTP-binding protein known to function in the regulation of cell growth and differentiation. Read-through transcripts containing this gene and a downstream gene have been identified, but they are not thought to encode a fusion protein. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jan 2012]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.89

Clinical Summary— DRG2

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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

49 VUS of 64 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 1.99

OE 0.57 (0.37–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.82Z-score

OE missense 0.66 (0.58–0.76)

152 obs / 229.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.37–0.89)

0≤0.351.4

Missense OE?0.66 (0.58–0.76)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 14 / 24.7Missense obs/exp: 152 / 229.7Syn Z: 0.16

This gene — mechanism propensity

0.77top 25%

GOF

0.5268th %ile

LOF

0.2873th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign1

Benign3

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	48	1	0	49
Likely Benign	1	0	0	1
Benign	1	0	2	3
Total	50	1	2	53

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

View in ClinVar →

116 pathogenic / likely-pathogenic (of 123) ClinVar copy-number / structural variants overlap DRG2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →