N4BP2L1

Chr 13

NEDD4 binding protein 2 like 1

Also known as: CG018

NCBI Gene: 90634 ENSG00000139597 UniProt: Q5TBK1

N4BP2L1 encodes a protein that may function in adipocyte differentiation and triglyceride accumulation, though its precise role remains unclear. The gene is highly constrained against loss-of-function variants (pLI = 0.84, LOEUF = 0.45), suggesting that mutations would likely cause developmental or neurological phenotypes, but specific associated diseases have not yet been definitively established in the literature.

ResearchSummary from UniProt

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.845

Z-score 2.72

OE 0.10 (0.03–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.33Z-score

OE missense 0.67 (0.56–0.80)

86 obs / 128.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.03–0.45)

0≤0.351.4

Missense OE?0.67 (0.56–0.80)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 1 / 10.5Missense obs/exp: 86 / 128.3Syn Z: 0.47

Background carrier burden — how many people carry a rare variant somewhere in N4BP2L1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

343 rare PASS variants

Rare truncating (LoF)

1 in 1,800

65 rare PASS variants

Rare synonymous (reference)

1 in 890

114 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for N4BP2L1. 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 250	1 in 2,400
South Asian	~43k	1 in 200	1 in 3,700
Remaining (unassigned)	~30k	1 in 270	1 in 2,200
European (Finnish)	~27k	1 in 1,100	1 in 4,300
Admixed American	~22k	1 in 250	1 in 2,000
African / African American	~21k	1 in 210	1 in 2,700
East Asian	~20k	1 in 270	1 in 2,400
Ashkenazi Jewish	~13k	1 in 550	1 in 850
Middle Eastern	~2,884	1 in 410	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓