RIPPLY1

Chr X

ripply transcriptional repressor 1

The protein functions as a transcriptional repressor essential for somite segmentation during embryonic development, terminating the segmentation program in presomitic mesoderm and maintaining rostrocaudal polarity in somites. Mutations cause vertebral segmentation defects with autosomal dominant inheritance. The gene shows low constraint against loss-of-function variants, suggesting tolerance to protein-truncating mutations.

Summary from RefSeq, UniProt
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0
Active trials
2
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.77
LOEUF
DN
Mechanism· predicted
Clinical SummaryRIPPLY1
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.77LOEUF
pLI 0.009
Z-score 0.31
OE 0.82 (0.371.77)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.11Z-score
OE missense 0.96 (0.761.21)
49 obs / 51.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.82 (0.371.77)
00.351.4
Missense OE0.96 (0.761.21)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 3 / 3.6Missense obs/exp: 49 / 51.3Syn Z: -0.04
DN
0.6357th %ile
GOF
0.5464th %ile
LOF
0.4529th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RIPPLY1 · 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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