GLDC

glycine decarboxylase

Basic information

Region (hg38): 9:6532467-6645729

Links

ENSG00000178445 ∙ NCBI:2731 ∙ OMIM:238300 ∙ HGNC:4313 ∙ Uniprot:P23378 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycine encephalopathy (Definitive), mode of inheritance: AR
• glycine encephalopathy (Strong), mode of inheritance: AR
• neonatal glycine encephalopathy (Supportive), mode of inheritance: AR
• infantile glycine encephalopathy (Supportive), mode of inheritance: AR
• atypical glycine encephalopathy (Supportive), mode of inheritance: Unknown
• glycine encephalopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycine encephalopathy 1	AR	Biochemical	Treatment may be less effective for individuals with severe disease; however, aggressive early treatment with sodium benzoate and N-methyl D-aspartate receptor site antagonists in individuals with variants associated with residual GCS enzyme activity have been reported to result in improved outcomes	Biochemical; Neurologic; Ophthalmologic	10873393; 12402263; 15077252; 15236413; 15851735; 16151895; 16404748; 16450403; 17361008; 20301531; 20933183; 21411353; 23349517

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLDC gene.

• Glycine encephalopathy (149 variants)
• Glycine encephalopathy 1 (10 variants)
• not provided (9 variants)
• GLDC-related disorder (4 variants)
• Inborn genetic diseases (2 variants)
• Smith-Magenis Syndrome-like (1 variants)
• Generalized epilepsy;Obesity;Global developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLDC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	589	8	600
missense	28	75	545	17	1	666
nonsense	46	56	2			104
start loss	2					2
frameshift	52	41				93
inframe indel	1	1	6			8
splice donor/acceptor (+/-2bp)	21	41	2			64
splice region	1	6	36	121	1	165
non coding			16	386	95	497
Total	150	214	574	992	104

Highest pathogenic variant AF is 0.0000855

Variants in GLDC

This is a list of pathogenic ClinVar variants found in the GLDC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-6532471-G-A		Glycine encephalopathy	Uncertain significance (Jan 13, 2018)
9-6532477-G-A		Glycine encephalopathy	Benign (Jan 13, 2018)
9-6532510-TAA-T		Glycine encephalopathy	Uncertain significance (Jun 14, 2016)
9-6532521-A-C		Glycine encephalopathy	Uncertain significance (Jan 13, 2018)
9-6532544-G-A		Glycine encephalopathy	Benign (Jan 13, 2018)
9-6532607-C-G		Glycine encephalopathy	Benign (Jan 12, 2018)
9-6532607-C-T		Glycine encephalopathy	Uncertain significance (Jan 12, 2018)
9-6532639-C-A		Glycine encephalopathy	Uncertain significance (Jan 12, 2018)
9-6532672-C-A		Glycine encephalopathy	Uncertain significance (Jan 13, 2018)
9-6532760-C-T		Glycine encephalopathy	Likely benign (Jul 26, 2018)
9-6532781-C-A		Glycine encephalopathy	Likely benign (Jan 12, 2018)
9-6532782-A-C		Glycine encephalopathy	Uncertain significance (Jan 12, 2018)
9-6532788-G-C		Glycine encephalopathy	Likely benign (Jan 13, 2018)
9-6532829-G-A		Glycine encephalopathy	Uncertain significance (Jan 13, 2018)
9-6532855-C-T			Likely benign (Aug 25, 2018)
9-6532902-T-A		Glycine encephalopathy	Uncertain significance (Jan 13, 2018)
9-6533010-C-G		not specified • Glycine encephalopathy	Benign (Jul 10, 2021)
9-6533012-G-C		Glycine encephalopathy	Uncertain significance (Apr 06, 2018)
9-6533018-TA-T		Glycine encephalopathy	Uncertain significance (Jul 15, 2022)
9-6533023-A-T		Glycine encephalopathy	Likely benign (Feb 18, 2020)
9-6533026-C-T		Glycine encephalopathy	Likely benign (Jan 12, 2024)
9-6533027-G-A		Glycine encephalopathy	Uncertain significance (May 03, 2022)
9-6533030-C-A		Glycine encephalopathy	Uncertain significance (Oct 24, 2021)
9-6533030-C-T		Glycine encephalopathy	Uncertain significance (Jan 14, 2022)
9-6533032-C-G		Glycine encephalopathy	Uncertain significance (Feb 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLDC	protein_coding	protein_coding	ENST00000321612	25	113187

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.58e-28	0.00238	125639	0	109	125748	0.000434

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.59	645	541	1.19	0.0000303	6656
Missense in Polyphen		256	245.66	1.0421		2936
Synonymous	-4.81	292	205	1.43	0.0000124	1961
Loss of Function	0.913	46	53.2	0.865	0.00000292	645

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000720	0.000720
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000218	0.000217
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000591	0.000589
Middle Eastern	0.000218	0.000217
South Asian	0.000426	0.000425
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH). {ECO:0000269|PubMed:1993704, ECO:0000269|PubMed:1996985, ECO:0000269|PubMed:28244183}.
• Disease: DISEASE: Non-ketotic hyperglycinemia (NKH) [MIM:605899]: Autosomal recessive disease characterized by accumulation of a large amount of glycine in body fluid and by severe neurological symptoms. {ECO:0000269|PubMed:11286506, ECO:0000269|PubMed:11592811, ECO:0000269|PubMed:1634607, ECO:0000269|PubMed:1996985, ECO:0000269|PubMed:28244183, ECO:0000269|PubMed:28737873}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycine, serine and threonine metabolism - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Ammonia Recycling;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);Glycine degradation;Metabolism of amino acids and derivatives;Glycine Serine metabolism;Metabolism;Glyoxylate metabolism and glycine degradation;Glycine, serine, alanine and threonine metabolism;glycine cleavage (Consensus)

Recessive Scores

• pRec: 0.312

Intolerance Scores

• loftool: 0.0943
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.41

Haploinsufficiency Scores

• pHI: 0.551
• hipred: N
• hipred_score: 0.441
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.918

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gldc
• Phenotype: renal/urinary system phenotype; skeleton phenotype; vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: glycine catabolic process;glycine decarboxylation via glycine cleavage system;electron transport chain;response to methylamine;response to lipoic acid;cellular response to leukemia inhibitory factor
• Cellular component: nucleus;mitochondrion;mitochondrial matrix;plasma membrane;glycine cleavage complex
• Molecular function: glycine dehydrogenase (decarboxylating) activity;electron transfer activity;glycine binding;lyase activity;enzyme binding;pyridoxal phosphate binding;protein homodimerization activity;pyridoxal binding