NGLY1

Chr 3AR

N-glycanase 1

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

NCBI Gene: 55768 ENSG00000151092 UniProt: Q96IV0 OMIM: 610661

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that catalyzes hydrolysis of an N(4)-(acetyl-beta-D-glucosaminyl) asparagine residue to N-acetyl-beta-D-glucosaminylamine and a peptide containing an aspartate residue. The encoded enzyme may play a role in the proteasome-mediated degradation of misfolded glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.951 OMIM phenotype

Clinical Summary— NGLY1

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Gene-Disease Validity (ClinGen)

congenital disorder of deglycosylation 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

133 unique Pathogenic / Likely Pathogenic· 333 VUS of 943 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — NGLY1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.80

OE 0.68 (0.50–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.07Z-score

OE missense 1.01 (0.92–1.11)

336 obs / 332.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.68 (0.50–0.95)

0≤0.351.4

Missense OE?1.01 (0.92–1.11)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 26 / 38.0Missense obs/exp: 336 / 332.3Syn Z: 0.38

ClinVar Variant Classifications

943 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic87

Likely Pathogenic46

VUS333

Likely Benign398

Benign42

Conflicting24

Pathogenic

Likely Pathogenic

333

VUS

398

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	75	5	7	0	87
Likely Pathogenic	38	6	2	0	46
VUS	3	305	20	5	333
Likely Benign	0	13	165	220	398
Benign	0	0	40	2	42
Conflicting	—				24
Total	116	329	234	227	930

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap NGLY1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →