RPRD1A

Chr 18

regulation of nuclear pre-mRNA domain containing 1A

Also known as: HsT3101, P15RS

This gene encodes a transcription regulatory protein that interacts with RNA polymerase II and participates in dephosphorylation of its C-terminal domain, while also functioning as a negative regulator of cell cycle progression. Mutations cause autosomal recessive neurodevelopmental disorder with epilepsy, cataracts, and developmental delay. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.58), consistent with its role in essential cellular processes.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
47
P/LP submissions
0%
P/LP missense
0.58
LOEUF
DN
Mechanism· predicted
Clinical SummaryRPRD1A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 26 VUS of 82 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.222
Z-score 2.76
OE 0.25 (0.120.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.94Z-score
OE missense 0.57 (0.480.68)
92 obs / 161.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.120.58)
00.351.4
Missense OE0.57 (0.480.68)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 4 / 15.8Missense obs/exp: 92 / 161.4Syn Z: -0.37
DN
0.6745th %ile
GOF
0.5758th %ile
LOF
0.3842th %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

82 submitted variants in ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic3
VUS26
Likely Benign1
42
Pathogenic
3
Likely Pathogenic
26
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
0
3
0
3
VUS
0
21
5
0
26
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02151072

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

View in ClinVar →

Protein Context — Lollipop Plot

RPRD1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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