RPRD2

Chr 1

regulation of nuclear pre-mRNA domain containing 2

Also known as: HSPC099, KIAA0460

NCBI Gene: 23248 ENSG00000163125 UniProt: Q5VT52 OMIM: 614695

Predicted to enable RNA polymerase II complex binding activity. Predicted to be involved in mRNA 3'-end processing. Part of transcription preinitiation complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.06

Clinical Summary— RPRD2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

154 VUS of 176 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.06LOEUF

pLI 1.000

Z-score 6.31

OE 0.00 (0.00–0.06)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.12Z-score

OE missense 0.79 (0.74–0.84)

623 obs / 790.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.06)

0≤0.351.4

Missense OE?0.79 (0.74–0.84)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 0 / 46.4Missense obs/exp: 623 / 790.7Syn Z: 0.37

This gene — mechanism propensity

0.18100th %ile

GOF

0.1699th %ile

LOF

0.87top 5%

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

LOFprediction above median · LOEUF 0.06

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

176 submitted variants in ClinVar

ClinVar

Classification Summary

VUS154

Likely Benign8

Benign1

154

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	154	0	154
Likely Benign	4	4	8
Benign	0	1	1
Total	158	5	163

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap RPRD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →