RAP2A

Chr 13

RAP2A, member of RAS oncogene family

Also known as: K-REV, KREV, RAP2, RbBP-30

RAP2A encodes a small GTP-binding protein that cycles between active and inactive forms to regulate neuronal dendrite development, cytoskeletal rearrangements, cell migration, and cell adhesion through interactions with downstream effectors including MAP4K4 and TNIK. Mutations cause autosomal dominant neurodevelopmental disorder with epilepsy, affecting the nervous system primarily. The gene is highly constrained against loss-of-function variants (pLI = 0.85, LOEUF = 0.48), indicating that complete loss of protein function is likely not tolerated.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 0.48
Clinical SummaryRAP2A
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.851
Z-score 2.32
OE 0.00 (0.000.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.56Z-score
OE missense 0.31 (0.240.41)
34 obs / 109.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.48)
00.351.4
Missense OE0.31 (0.240.41)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 0 / 6.2Missense obs/exp: 34 / 109.4Syn Z: -1.04
DN
0.5575th %ile
GOF
0.7126th %ile
LOF
0.53top 25%

The highest-scoring mechanism for this gene is gain-of-function.

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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RAP2A · 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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