N4BP2L2

Chr 13

NEDD4 binding protein 2 like 2

Also known as: 92M18.3, CG005, CG016, PFAAP5

NCBI Gene: 10443ENSG00000244754UniProt: Q92802OMIM: 615788

The N4BP2L2 protein enables enzyme binding and functions as part of a transcription repressor complex that regulates hematopoietic stem cell differentiation and proliferation. Mutations cause autosomal recessive developmental delay with dysmorphic facies and dental anomalies, typically presenting in early childhood. This gene shows minimal constraint against loss-of-function variants based on population genetics data.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 0.90
Clinical Summary— N4BP2L2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
47 unique Pathogenic / Likely Pathogenic· 24 VUS of 93 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
0.90LOEUF
pLI 0.000
Z-score 1.98
OE 0.62 (0.43–0.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.40Z-score
OE missense 0.94 (0.86–1.03)
343 obs / 364.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.62 (0.43–0.90)
0≤0.351.4
Missense OE0.94 (0.86–1.03)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 19 / 30.9Missense obs/exp: 343 / 364.5Syn Z: 0.95
DN
0.6357th %ile
GOF
0.4678th %ile
LOF
0.3552th %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

93 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
VUS24
Likely Benign4
47
Pathogenic
24
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
46
0
47
Likely Pathogenic
0
0
0
0
0
VUS
1
16
7
0
24
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total22053075

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

View in ClinVar →

Protein Context — Lollipop Plot

N4BP2L2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Identification of hub genes and their correlation with immune infiltrating cells in membranous nephropathy: an integrated bioinformatics analysis
Han M et al.·Eur J Med Res
2023
Biomarker Identification in Membranous Nephropathy Using a Long Non-coding RNA-Mediated Competitive Endogenous RNA Network.
Zhou G et al.·Interdiscip Sci
2021
Comprehensive evaluation of circRNAs in cirrhotic cardiomyopathy before and after liver transplantation.
Zhang Y et al.·Int Immunopharmacol
2023
Four Autophagy-Related Long Noncoding RNAs Provide Coexpression and ceRNA Mechanisms in Retinoblastoma through Bioinformatics and Experimental Evidence
Ren H et al.·ACS Omega
2021Functional
A genome-wide study of the relationship between chromosomal abnormalities and gene expression in colorectal tumors
Sugai T et al.·Genes Chromosomes Cancer
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients