NAE1

Chr 16AR

NEDD8 activating enzyme E1 subunit 1

Also known as: A-116A10.1, APPBP1, HPP1, NEDFIH, ula-1

The NAE1 protein serves as the regulatory subunit of the UBA3-NAE1 E1 enzyme that activates NEDD8, a ubiquitin-like protein essential for cell cycle progression and neddylation processes involved in cell growth and development. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia. This gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.941 OMIM phenotype
Clinical SummaryNAE1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.85
OE 0.68 (0.500.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.09Z-score
OE missense 0.81 (0.730.91)
218 obs / 268.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.500.94)
00.351.4
Missense OE0.81 (0.730.91)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 26 / 38.3Missense obs/exp: 218 / 268.3Syn Z: 1.04

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NAE1 · 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.

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Clinical Literature
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