NUS1

Chr 6ARAD

NUS1 dehydrodolichyl diphosphate synthase subunit

Also known as: C6orf68, CDG1AA, MGC:7199, MRD55, NgBR, TANGO14

This protein is essential for dolichol synthesis and protein glycosylation as a subunit of cis-prenyltransferase in the endoplasmic reticulum. Mutations cause congenital disorder of glycosylation type 1aa and intellectual developmental disorder with seizures through loss-of-function mechanisms. The condition follows both autosomal recessive and autosomal dominant inheritance patterns.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAR/ADLOEUF 0.252 OMIM phenotypes
Clinical SummaryNUS1
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Gene-Disease Validity (ClinGen)
progressive myoclonus epilepsy · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.981
Z-score 3.23
OE 0.00 (0.000.25)
Highly constrained

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

Missense Constraint
0.88Z-score
OE missense 0.80 (0.690.93)
126 obs / 156.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.25)
00.351.4
Missense OE0.80 (0.690.93)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 0 / 12.1Missense obs/exp: 126 / 156.9Syn Z: -0.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongNUS1-related epilepsy and intellectual disabilityLOFAD
DN
0.3594th %ile
GOF
0.3094th %ile
LOF
0.72top 10%

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

LOFprediction above median · 1 literature citation · LOEUF 0.25

Literature Evidence

LOFTwo patients were found by whole-genome sequencing of 197 individuals with developmental epileptic encephalopathy; the third patient was found by clinical exome sequencing from another patient cohort. Studies of the variants and studies of patients cells were not performed, but Hamdan et al. (2017) PMID:29100083

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NUS1 · 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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC