N4BP2L2

Chr 13

NEDD4 binding protein 2 like 2

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

NCBI Gene: 10443 ENSG00000244754 UniProt: Q92802

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.

ResearchSummary from RefSeq

Enables enzyme binding activity. Involved in negative regulation of hematopoietic stem cell differentiation and positive regulation of hematopoietic stem cell proliferation. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.62 (0.43–0.90)

0≤0.351.4

Missense OE?0.94 (0.86–1.03)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 19 / 30.9Missense obs/exp: 343 / 364.5Syn Z: 0.95

Background carrier burden — how many people carry a rare variant somewhere in N4BP2L2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 50

1,471 rare PASS variants

Rare truncating (LoF)

1 in 320

293 rare PASS variants

Rare synonymous (reference)

1 in 170

472 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for N4BP2L2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 64	1 in 490
South Asian	~43k	1 in 33	1 in 190
Remaining (unassigned)	~30k	1 in 37	1 in 240
European (Finnish)	~27k	1 in 190	1 in 2,600
Admixed American	~22k	1 in 32	1 in 210
African / African American	~21k	1 in 37	1 in 310
East Asian	~20k	1 in 46	1 in 660
Ashkenazi Jewish	~13k	1 in 170	1 in 760
Middle Eastern	~2,884	1 in 62	1 in 340

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 5 coding exons well covered in gnomAD exomes; exons 4, 5 marginal. Genomes: all 5.? see exons ↓