GCSH

Chr 16AR

glycine cleavage system protein H

Also known as: GCE, MMDS7, NKH

The H protein encoded by GCSH shuttles the methylamine group of glycine from the P protein to the T protein in the mitochondrial glycine cleavage system and plays a pivotal role in the lipoylation of enzymes involved in cellular energetics. Mutations cause multiple mitochondrial dysfunctions syndrome 7 with autosomal recessive inheritance. This gene shows low constraint to loss-of-function variants, suggesting tolerance to complete protein loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.421 OMIM phenotype
Clinical SummaryGCSH
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Gene-Disease Validity (ClinGen)
multiple mitochondrial dysfunctions syndrome 7 · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.42LOEUF
pLI 0.002
Z-score 0.79
OE 0.68 (0.361.42)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.09Z-score
OE missense 0.97 (0.801.18)
70 obs / 72.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.361.42)
00.351.4
Missense OE0.97 (0.801.18)
00.61.4
Synonymous OE0.74
01.21.6
LoF obs/exp: 5 / 7.3Missense obs/exp: 70 / 72.2Syn Z: 1.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongGCSH-related glycine encephalopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6258th %ile
GOF
0.5170th %ile
LOF
0.3356th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GCSH · 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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