GLYR1

Chr 16

glyoxylate reductase 1 homolog

Also known as: BM045, HIBDL, N-PAC, NP60, NPAC, hNDF

NCBI Gene: 84656 ENSG00000140632 OMIM: 610660

GLYR1 encodes a chromatin remodeling factor that destabilizes nucleosomes during transcriptional activation and regulates gene expression through histone modifications and interactions with histone-modifying enzymes. Mutations cause autosomal dominant neurodevelopmental disorder with developmental delay, intellectual disability, and variable features including seizures and behavioral abnormalities. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.195), reflecting its essential role in transcriptional regulation.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including chromatin-protein adaptor activity; methylated histone binding activity; and nucleosome binding activity. Involved in transcription elongation-coupled chromatin remodeling and transcription initiation-coupled chromatin remodeling. Located in cytosol and nucleoplasm. Part of nucleosome. Is active in chromatin. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.20

Clinical Summary— GLYR1

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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.

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ClinVar Variants

58 VUS of 87 total submissions

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?

0.20LOEUF

pLI 1.000

Z-score 4.94

OE 0.06 (0.02–0.20)

Highly constrained

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

Missense Constraint?

2.34Z-score

OE missense 0.64 (0.57–0.72)

215 obs / 335.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.20)

0≤0.351.4

Missense OE?0.64 (0.57–0.72)

0≤0.61.4

Synonymous OE?1.42

0≤1.21.6

LoF obs/exp: 2 / 32.3Missense obs/exp: 215 / 335.9Syn Z: -3.87

This gene — mechanism propensity

0.3495th %ile

GOF

0.3193th %ile

LOF

0.78top 5%

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

LOFprediction above median · LOEUF 0.20

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

87 submitted variants in ClinVar

ClinVar

Classification Summary

VUS58

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	58	0	58
Likely Benign	0	1	1
Benign	0	0	0
Total	58	1	59

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap GLYR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →