GPD1

protein-coding

glycerol-3-phosphate dehydrogenase 1

Gene summary

This gene encodes a member of the NAD-dependent glycerol-3-phosphate dehydrogenase family. The encoded protein plays a critical role in carbohydrate and lipid metabolism by catalyzing the reversible conversion of dihydroxyacetone phosphate (DHAP) and reduced nicotine adenine dinucleotide (NADH) to glycerol-3-phosphate (G3P) and NAD+. The encoded cytosolic protein and mitochondrial glycerol-3-phosphate dehydrogenase also form a glycerol phosphate shuttle that facilitates the transfer of reducing equivalents from the cytosol to mitochondria. Mutations in this gene are a cause of transient infantile hypertriglyceridemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

MANE transcript

NM_005276.4

Inheritance

ClinVar variants

P:28U:69B:53

Top phenotype

Hypertriglyceridemia, transient infantile

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr12:50,103,982-50,111,313

External References & Databases

Ensembl (ENSG00000167588)

Transcript & Mutation Effects

hg38 • Region Span ~7.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

transient infantile hypertriglyceridemia and hepatosteatosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013771

Submitter: Labcorp Genetics (formerly Invitae)

transient infantile hypertriglyceridemia and hepatosteatosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013771

Submitter: Genomics England PanelApp

transient infantile hypertriglyceridemia and hepatosteatosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013771

Submitter: Orphanet

transient infantile hypertriglyceridemia and hepatosteatosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013771

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hypertriglyceridemia, transient infantileAR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: 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

Refs: 22226083; 24549054

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPD1 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 104

Inborn genetic diseasesTotal: 59

Transient infantile hypertriglyceridemia and hepatosteatosisTotal: 28

GPD1-related disorderTotal: 18

not specifiedTotal: 14

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Inborn errors of metabolismTotal: 1

Familial hypercholesterolemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005276.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				36 clinvar		36
missense	2 clinvar	6 clinvar	64 clinvar	16 clinvar	1 clinvar	89
nonsense	3 clinvar	2 clinvar	1 clinvar			6
start loss			1 clinvar			1
frameshift	2 clinvar	5 clinvar				7
splice donor/acceptor (+/-2bp)	2 clinvar	6 clinvar	3 clinvar			11
Total	9	19	69	52	1	150

Highest pathogenic variant AF is 0.00006506213

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005276.4	RefSeq	NP_005267.2	8	MANE Select
ENST00000301149.8	Ensembl	ENSP00000301149.3	8	MANE Select
NM_001257199.2	RefSeq	NP_001244128.1	8	Standard
ENST00000547964.5	Ensembl	ENSP00000448244.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycerophospholipid metabolism - Homo sapiens (human)
Mitochondrial Electron Transport Chain
Familial lipoprotein lipase deficiency
Glycerol Phosphate Shuttle
Glycerolipid Metabolism

Biological Process

glycerol-3-phosphate metabolic process
gluconeogenesis
glycerophosphate shuttle
phosphatidic acid biosynthetic process
positive regulation of glycolytic process

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

Cellular Component

cytosol
glycerol-3-phosphate dehydrogenase complex
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000301149
Coding exons: 8
Length: 7501
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125748
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.167	199	206	0.967	0.0000117	2280
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.523

Intolerance Scores

LoFtool: 0.685
RVIS EVS: 0.15
RVIS percentile EVS: 64.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

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