This gene encodes a retinoic acid-induced protein with unknown specific function but likely involvement in development. Mutations cause X-linked intellectual disability with variable features that may include seizures, autism spectrum disorder, and developmental delays. The gene shows X-linked inheritance and high constraint against loss-of-function variants (LOEUF 0.66), suggesting intolerance to disruption.

OMIMResearchSummary from RefSeq
LOFmechanismLOEUF 0.66
Clinical SummaryRAI2
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADDisputed

Disputed — evidence questions this relationship

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
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ClinVar Variants
71 unique Pathogenic / Likely Pathogenic· 84 VUS of 208 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.66LOEUF
pLI 0.612
Z-score 2.15
OE 0.14 (0.050.66)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
-0.06Z-score
OE missense 1.01 (0.911.13)
217 obs / 214.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.14 (0.050.66)
00.351.4
Missense OE1.01 (0.911.13)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 1 / 7.2Missense obs/exp: 217 / 214.5Syn Z: -0.47
DN
0.3594th %ile
GOF
0.2995th %ile
LOF
0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

208 submitted variants in ClinVar

Classification Summary

Pathogenic69
Likely Pathogenic2
VUS84
Likely Benign6
Benign5
69
Pathogenic
2
Likely Pathogenic
84
VUS
6
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
69
0
69
Likely Pathogenic
0
0
2
0
2
VUS
0
73
11
0
84
Likely Benign
0
2
0
4
6
Benign
0
1
0
4
5
Total076828166

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

View in ClinVar →

Protein Context — Lollipop Plot

RAI2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗