GPD1L

glycerol-3-phosphate dehydrogenase 1 like

Basic information

Region (hg38): 3:32105689-32168709

Links

ENSG00000152642 ∙ NCBI:23171 ∙ OMIM:611778 ∙ HGNC:28956 ∙ Uniprot:Q8N335 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome 2 (Limited), mode of inheritance: Unknown
• Brugada syndrome 2 (Limited), mode of inheritance: AD
• Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brugada syndrome 2	AD	Cardiovascular; Pharmacogenomic	Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	Cardiovascular	11839626; 17967977; 17967976

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPD1L gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPD1L 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			2	88	4	94
missense			151	2		153
nonsense			2			2
start loss			1			1
frameshift			5			5
inframe indel			2			2
splice donor/acceptor (+/-2bp)			4	1		5
splice region			3	13	2	18
non coding			2	42	31	75
Total	0	0	169	133	35

Variants in GPD1L

This is a list of pathogenic ClinVar variants found in the GPD1L region.

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

Position	Type	Phenotype	Significance	ClinVar
3-32106298-G-A			Benign (Jul 05, 2018)
3-32106347-G-A			Likely benign (Jun 14, 2018)
3-32106421-G-A			Benign (Jun 19, 2018)
3-32106479-CGGGCCTGGAGGCCGGCCG-C			Benign (Mar 21, 2019)
3-32106485-T-G			Benign (Jun 19, 2018)
3-32106580-G-A		Brugada syndrome	Uncertain significance (Jun 14, 2016)
3-32106593-C-T			Benign (Mar 03, 2015)
3-32106665-C-G		not specified	Likely benign (Dec 19, 2016)
3-32106712-A-G		Brugada syndrome • Cardiovascular phenotype	Uncertain significance (Oct 25, 2021)
3-32106716-C-T			Uncertain significance (Apr 06, 2023)
3-32106718-GC-G			Uncertain significance (Aug 20, 2014)
3-32106719-C-T		Cardiovascular phenotype	Uncertain significance (Apr 18, 2024)
3-32106720-G-A		Brugada syndrome	Likely benign (Jan 17, 2024)
3-32106722-C-A		Cardiovascular phenotype	Uncertain significance (Feb 22, 2023)
3-32106722-C-T		Brugada syndrome • Cardiovascular phenotype	Uncertain significance (Feb 13, 2023)
3-32106725-C-T		Brugada syndrome	Uncertain significance (Feb 25, 2020)
3-32106726-C-T		Brugada syndrome	Likely benign (Feb 27, 2018)
3-32106738-C-T		Brugada syndrome	Likely benign (Jan 28, 2022)
3-32106749-C-T		Brugada syndrome	Uncertain significance (Sep 01, 2021)
3-32106751-G-A		Brugada syndrome	Uncertain significance (May 07, 2019)
3-32106752-G-A		Brugada syndrome	Uncertain significance (Jan 12, 2022)
3-32106755-A-G		Brugada syndrome	Uncertain significance (Dec 13, 2023)
3-32106759-G-A		Brugada syndrome • Cardiovascular phenotype	Uncertain significance (Mar 13, 2023)
3-32106775-T-C		not specified	Uncertain significance (Feb 05, 2023)
3-32106777-G-C		Brugada syndrome	Likely benign (Apr 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPD1L	protein_coding	protein_coding	ENST00000282541	8	63025

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0382	0.956	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.08	157	200	0.786	0.0000114	2307
Missense in Polyphen		55	77.775	0.70717		913
Synonymous	0.0118	78	78.1	0.998	0.00000518	688
Loss of Function	2.39	5	15.0	0.334	7.04e-7	184

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000248	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium current; cardiac sodium current may also be reduced due to alterations of NAD(H) balance induced by DPD1L. {ECO:0000269|PubMed:19666841, ECO:0000269|PubMed:19745168}.
• Pathway: Glycerophospholipid metabolism - Homo sapiens (human);Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Metabolism of lipids;Metabolism;Glycerophospholipid biosynthesis;Phospholipid metabolism;Synthesis of PA (Consensus)

Recessive Scores

• pRec: 0.174

Intolerance Scores

• loftool: 0.504
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.36

Haploinsufficiency Scores

• pHI: 0.572
• hipred: N
• hipred_score: 0.276
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gpd1l

Gene ontology

• Biological process: action potential;regulation of heart rate;carbohydrate metabolic process;phosphatidic acid biosynthetic process;positive regulation of sodium ion transport;NAD metabolic process;negative regulation of peptidyl-serine phosphorylation;glycerol-3-phosphate catabolic process;regulation of ventricular cardiac muscle cell membrane depolarization;ventricular cardiac muscle cell action potential;negative regulation of protein kinase C signaling;positive regulation of protein localization to cell surface;regulation of sodium ion transmembrane transporter activity
• Cellular component: cytosol;plasma membrane;glycerol-3-phosphate dehydrogenase complex;extracellular exosome
• Molecular function: glycerol-3-phosphate dehydrogenase [NAD+] activity;sodium channel regulator activity;protein homodimerization activity;ion channel binding;NAD binding