RPAIN

Chr 17

RPA interacting protein

Also known as: HRIP, RIP

The RPAIN protein mediates nuclear import of the RPA complex and its localization to PML bodies, where it participates in DNA metabolism functions. Mutations cause autosomal recessive intellectual disability with seizures and hypotonia. This gene shows very high constraint against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.84
Clinical SummaryRPAIN
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — 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
1.84LOEUF
pLI 0.000
Z-score -0.84
OE 1.27 (0.831.84)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.14Z-score
OE missense 0.97 (0.831.12)
121 obs / 125.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.27 (0.831.84)
00.351.4
Missense OE0.97 (0.831.12)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 14 / 11.0Missense obs/exp: 121 / 125.4Syn Z: -0.71
DN
0.6453th %ile
GOF
0.3392th %ile
LOF
0.3843th %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

RPAIN · 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

No open access results found