NRARP

Chr 9

NOTCH regulated ankyrin repeat protein

The NRARP protein functions as a downstream effector of Notch signaling that regulates angiogenesis, somite segmentation during development, and integrates Notch and Wnt signaling pathways. Mutations in NRARP cause autosomal recessive spondylocostal dysostosis, characterized by vertebral segmentation defects and rib malformations. This gene shows relatively low constraint to loss-of-function mutations (LOEUF 1.5), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.50
Clinical SummaryNRARP
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.50LOEUF
pLI 0.209
Z-score 1.03
OE 0.35 (0.121.50)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
2.33Z-score
OE missense 0.21 (0.140.32)
14 obs / 67.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.35 (0.121.50)
00.351.4
Missense OE0.21 (0.140.32)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 1 / 2.9Missense obs/exp: 14 / 67.9Syn Z: 0.84
DN
0.5082th %ile
GOF
0.6345th %ile
LOF
0.4529th %ile

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

NRARP · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC