PRR18

Chr 6

proline rich 18

NCBI Gene: 285800 ENSG00000176381 UniProt: Q8N4B5

The PRR18 protein function is not well characterized in the provided data. Based on the gene constraint metrics showing moderate tolerance to loss-of-function variants (pLI: 0.46, LOEUF: 1.52), this gene does not appear to be under strong selective pressure. No specific disease associations or inheritance patterns are documented in the available information.

Research

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.52

Clinical Summary— PRR18

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

83 VUS of 87 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.52LOEUF

pLI 0.461

Z-score 1.17

OE 0.00 (0.00–1.52)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.89Z-score

OE missense 0.71 (0.57–0.89)

53 obs / 74.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.52)

0≤0.351.4

Missense OE?0.71 (0.57–0.89)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 0 / 1.6Missense obs/exp: 53 / 74.6Syn Z: 1.06

This gene — mechanism propensity

0.5082th %ile

GOF

0.6833th %ile

LOF

0.57top 25%

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

87 submitted variants in ClinVar

ClinVar

Classification Summary

VUS83

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	83	83
Likely Benign	4	4
Benign	0	0
Total	87	87

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

View in ClinVar →

51 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap PRR18 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →