NPIPB4

Chr 16

nuclear pore complex interacting protein family member B4

Also known as: 61E3.4

NPIPB4 encodes a protein predicted to be located in cellular membranes, though its specific function remains poorly characterized. The gene shows relatively low constraint against loss-of-function variants (pLI 0.18, LOEUF 0.96), suggesting tolerance to protein-disrupting mutations. No definitive disease associations have been established for NPIPB4 mutations in current medical literature.

ResearchSummary from RefSeq
MultiplemechanismLOEUF 0.96
Clinical SummaryNPIPB4
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.183
Z-score 1.64
OE 0.31 (0.120.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.45Z-score
OE missense 1.11 (0.971.26)
157 obs / 142.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.31 (0.120.96)
00.351.4
Missense OE1.11 (0.971.26)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 2 / 6.5Missense obs/exp: 157 / 142.0Syn Z: 0.04
DN
0.84top 10%
GOF
0.93top 5%
LOF
0.3746th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

NPIPB4 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found