GCSH

Chr 16AR

glycine cleavage system protein H

Also known as: GCE, MMDS7, NKH

Degradation of glycine is brought about by the glycine cleavage system, which is composed of four mitochondrial protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L protein (a lipoamide dehydrogenase). The protein encoded by this gene is the H protein, which transfers the methylamine group of glycine from the P protein to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH). Two transcript variants, one protein-coding and the other probably not protein-coding,have been found for this gene. Also, several transcribed and non-transcribed pseudogenes of this gene exist throughout the genome.[provided by RefSeq, Jan 2010]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Multiple mitochondrial dysfunctions syndrome 7MIM #620423
AR

Clinical highlights

Gene-disease validity (ClinGen)
multiple mitochondrial dysfunctions syndrome 7 · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
8
Pubs (1 yr)
P/LP submissions
P/LP missense
1.42
LOEUF
LOF
Mechanism· G2P
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GeneReview available — GCSH
Authoritative clinical overview · Recommended first read
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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 OE?0.68 (0.361.42)
00.351.4
Missense OE?0.97 (0.801.18)
00.61.4
Synonymous OE?0.74
01.21.6
LoF obs/exp: 5 / 7.3Missense obs/exp: 70 / 72.2Syn Z: 1.04

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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