PRUNE2

Chr 9

prune homolog 2 with BCH domain

Also known as: BMCC1, BNIPXL, C9orf65, KIAA0367

The protein suppresses RhoA activity to regulate stress fiber formation and cellular transformation, and is involved in post-endocytic trafficking through interaction with adaptor protein complexes. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, microcephaly, and seizures. This gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.72
Clinical SummaryPRUNE2
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
0.72LOEUF
pLI 0.000
Z-score 4.02
OE 0.58 (0.470.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.54Z-score
OE missense 0.96 (0.921.00)
1534 obs / 1594.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.470.72)
00.351.4
Missense OE0.96 (0.921.00)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 62 / 106.8Missense obs/exp: 1534 / 1594.6Syn Z: -0.16
DN
0.6356th %ile
GOF
0.4480th %ile
LOF
0.3067th %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

PRUNE2 · 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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