NGLY1

Chr 3AR

N-glycanase 1

Also known as: CDDG, CDG1V, PNG-1, PNG1, PNGase

The protein specifically deglycosylates misfolded N-linked glycoproteins in the cytoplasm to facilitate their degradation by the proteasome. Mutations cause congenital disorder of deglycosylation 1, an autosomal recessive condition with early onset developmental delay, hypotonia, seizures, and liver dysfunction. The gene is highly intolerant to loss-of-function variants, consistent with the severe phenotype observed in affected individuals.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.951 OMIM phenotype
Clinical SummaryNGLY1
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Gene-Disease Validity (ClinGen)
congenital disorder of deglycosylation 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
89 unique Pathogenic / Likely Pathogenic· 134 VUS of 600 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — NGLY1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.000
Z-score 1.80
OE 0.68 (0.500.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.07Z-score
OE missense 1.01 (0.921.11)
336 obs / 332.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.68 (0.500.95)
00.351.4
Missense OE1.01 (0.921.11)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 26 / 38.0Missense obs/exp: 336 / 332.3Syn Z: 0.38

ClinVar Variant Classifications

600 submitted variants in ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic25
VUS134
Likely Benign330
Benign28
Conflicting6
64
Pathogenic
25
Likely Pathogenic
134
VUS
330
Likely Benign
28
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
51
1
12
0
64
Likely Pathogenic
21
2
2
0
25
VUS
1
121
11
1
134
Likely Benign
0
4
142
184
330
Benign
0
0
28
0
28
Conflicting
6
Total73128195185587

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NGLY1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗