GPD1

glycerol-3-phosphate dehydrogenase 1

Basic information

Region (hg38): 12:50103981-50111313

Links

ENSG00000167588 ∙ NCBI:2819 ∙ OMIM:138420 ∙ HGNC:4455 ∙ Uniprot:P21695 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• transient infantile hypertriglyceridemia and hepatosteatosis (Strong), mode of inheritance: AR
• transient infantile hypertriglyceridemia and hepatosteatosis (Strong), mode of inheritance: AR
• transient infantile hypertriglyceridemia and hepatosteatosis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypertriglyceridemia, transient infantile	AR	Gastrointestinal	Individuals may present with failure to thrive and other sequelae of disease, and dietary management (with high-calorie, low-fat diet) has been described as beneficial	Gastrointestinal	22226083; 24549054

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPD1 gene.

• not provided (2 variants)
• Transient infantile hypertriglyceridemia and hepatosteatosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPD1 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			1	18	3	22
missense			35	7		42
nonsense	1		1			2
start loss			1			1
frameshift	1	1				2
inframe indel				1		1
splice donor/acceptor (+/-2bp)	1	1	1			3
splice region			2	1		3
non coding				14	5	19
Total	3	2	39	40	8

Variants in GPD1

This is a list of pathogenic ClinVar variants found in the GPD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-50104051-A-G		Transient infantile hypertriglyceridemia and hepatosteatosis	Uncertain significance (May 06, 2024)
12-50104084-G-A		Transient infantile hypertriglyceridemia and hepatosteatosis	Uncertain significance (Jun 03, 2020)
12-50104089-C-T			Likely benign (Oct 21, 2021)
12-50104108-A-G			Likely benign (Apr 28, 2022)
12-50104356-T-G			Benign (Sep 21, 2018)
12-50104365-C-A			Likely benign (May 19, 2019)
12-50104564-C-T			Likely benign (Dec 27, 2021)
12-50104586-C-T			Likely benign (Nov 16, 2023)
12-50104592-G-A			Likely benign (Dec 04, 2023)
12-50104596-G-A		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
12-50104615-A-G			Uncertain significance (Jun 09, 2021)
12-50104636-G-A			Uncertain significance (Jun 28, 2023)
12-50104637-G-A			Likely benign (May 22, 2023)
12-50104648-G-A		Transient infantile hypertriglyceridemia and hepatosteatosis	Pathogenic (Jun 06, 2024)
12-50104665-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 23, 2021)
12-50104666-T-A			Uncertain significance (May 11, 2023)
12-50104691-C-A			Benign/Likely benign (Jul 01, 2024)
12-50104692-A-G		GPD1-related disorder	Benign/Likely benign (Jan 08, 2024)
12-50104737-T-C			Likely benign (Oct 10, 2023)
12-50104748-TGTG-T		Transient infantile hypertriglyceridemia and hepatosteatosis	Likely pathogenic (-)
12-50104752-G-A		Transient infantile hypertriglyceridemia and hepatosteatosis	Pathogenic (May 22, 2022)
12-50104771-G-A			Benign (Jan 25, 2024)
12-50105281-C-T			Likely benign (Sep 23, 2019)
12-50105534-G-C			Likely benign (Nov 14, 2023)
12-50105562-TGTG-T		Inborn genetic diseases	Likely benign (Apr 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPD1	protein_coding	protein_coding	ENST00000301149	8	7501

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00555	0.973	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.167	199	206	0.967	0.0000117	2280
Missense in Polyphen		61	65.73	0.92804		741
Synonymous	-0.507	88	82.2	1.07	0.00000494	690
Loss of Function	2.02	6	14.2	0.423	6.00e-7	179

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000364	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.000219	0.000217
South Asian	0.000329	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Hypertriglyceridemia, transient infantile (HTGTI) [MIM:614480]: An autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. {ECO:0000269|PubMed:22226083, ECO:0000269|PubMed:24549054}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Mitochondrial Electron Transport Chain;Familial lipoprotein lipase deficiency;Glycerol Phosphate Shuttle;Glycerolipid Metabolism;Glycerol Kinase Deficiency;Phospholipid Biosynthesis;D-glyceric acidura;HIF1A and PPARG regulation of glycolysis;Triacylglyceride Synthesis;Metabolism of lipids;Metabolism;glycerol-3-phosphate shuttle;Glycerophospholipid metabolism;Glycerophospholipid biosynthesis;Phospholipid metabolism;Synthesis of PA (Consensus)

Recessive Scores

• pRec: 0.523

Intolerance Scores

• loftool: 0.685
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.61

Haploinsufficiency Scores

• pHI: 0.799
• hipred: N
• hipred_score: 0.332
• ghis: 0.442

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gpd1
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: glycerol-3-phosphate metabolic process;gluconeogenesis;glycerophosphate shuttle;phosphatidic acid biosynthetic process;positive regulation of glycolytic process;glycerol-3-phosphate catabolic process;cellular response to cAMP;cellular response to tumor necrosis factor
• Cellular component: cytosol;glycerol-3-phosphate dehydrogenase complex;extracellular exosome
• Molecular function: glycerol-3-phosphate dehydrogenase [NAD+] activity;glycerol-3-phosphate dehydrogenase (quinone) activity;protein homodimerization activity;glycerol-3-phosphate dehydrogenase [NAD(P)+] activity;NAD binding