GPD1L

Chr 3AD

glycerol-3-phosphate dehydrogenase 1 like

Also known as: GPD1-L

NCBI Gene: 23171ENSG00000152642UniProt: Q8N335OMIM: 611778

This protein catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate and binds to the cardiac sodium channel SCN5A at the plasma membrane, playing a critical role in regulating cardiac sodium current. Mutations cause Brugada syndrome type 2, a cardiac arrhythmia disorder that can present with sudden cardiac death and has been associated with sudden infant death syndrome (SIDS). Inheritance is autosomal dominant.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.701 OMIM phenotype
Clinical Summary— GPD1L
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Gene-Disease Validity (ClinGen)
Brugada syndrome 1 · ADDisputed

Disputed — evidence questions this relationship

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
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ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 218 VUS of 485 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — GPD1L
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.70LOEUF
pLI 0.038
Z-score 2.39
OE 0.33 (0.17–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.08Z-score
OE missense 0.79 (0.69–0.90)
157 obs / 199.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.17–0.70)
0≤0.351.4
Missense OE0.79 (0.69–0.90)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 5 / 15.0Missense obs/exp: 157 / 199.8Syn Z: 0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedGPD1L-related Brugada syndromeOTHERAD
DN
0.7326th %ile
GOF
0.6248th %ile
LOF
0.2680th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

485 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS218
Likely Benign180
Benign42
Conflicting23
15
Pathogenic
1
Likely Pathogenic
218
VUS
180
Likely Benign
42
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
1
0
1
VUS
16
191
11
0
218
Likely Benign
0
2
68
110
180
Benign
0
0
37
5
42
Conflicting
—23
Total16193132115479

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GPD1L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
GPD1L supports glycerol-3-phosphate and triacylglycerol synthesis and promotes tumor progression in HCC.
Yu TC et al.·Hepatology
2026
GPD1L-A306del modifies sodium current in a family carrying the dysfunctional SCN5A-G1661R mutation associated with Brugada syndrome.
Semino F et al.·Pflugers Arch
2024Functional
Identification of GPD1L as a Potential Prognosis Biomarker and Associated with Immune Infiltrates in Lung Adenocarcinoma.
Fan Z et al.·Mediators Inflamm
2023
GPD1L-Mediated Glycerophospholipid Metabolism Dysfunction in Women With Diminished Ovarian Reserve: Insights From Pseudotargeted Metabolomic Analysis of Follicular Fluid.
Wu J et al.·Cell Prolif
2025
Calycosin Inhibits the Malignant Behaviors of Lung Adenocarcinoma Cells by Regulating the circ_0001946/miR-21/GPD1L/HIF-1α Signaling Axis.
Zhou L et al.·Dis Markers
2022
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients