NEURL4

Chr 17

neuralized E3 ubiquitin protein ligase 4

NCBI Gene: 84461 ENSG00000215041 UniProt: Q96JN8 OMIM: 615865

NEURL4 encodes a protein that promotes CCP110 ubiquitination and proteasome-dependent degradation, maintaining normal centriolar homeostasis and preventing formation of ectopic microtubular organizing centers. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.21), suggesting that mutations would likely cause severe developmental phenotypes. However, no specific human disease has been definitively associated with NEURL4 mutations to date.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is predicted and it includes two isoforms resulting from two alternatively spliced transcript variants. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.21

Clinical Summary— NEURL4

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.21LOEUF

pLI 1.000

Z-score 6.72

OE 0.12 (0.07–0.21)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.95Z-score

OE missense 0.74 (0.69–0.78)

732 obs / 993.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.07–0.21)

0≤0.351.4

Missense OE?0.74 (0.69–0.78)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 8 / 67.6Missense obs/exp: 732 / 993.9Syn Z: 0.11

This gene — mechanism propensity

0.3196th %ile

GOF

0.4184th %ile

LOF

0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.