GPD1L

Chr 3

glycerol-3-phosphate dehydrogenase 1 like

Also known as: GPD1-L

NCBI Gene: 23171 ENSG00000152642 UniProt: Q8N335

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS). [provided by RefSeq, Jul 2010]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBrugada syndrome 2

Clinical highlights

Gene–disease validity (ClinGen)

Disputed · Brugada syndrome 1 · AD · ClinGen 2017

evidence questions this relationship

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

LOEUF

Mechanism· predicted

📖

GeneReview available — GPD1L

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.33 (0.17–0.70)

0≤0.351.4

Missense OE?0.79 (0.69–0.90)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 5 / 15.0Missense obs/exp: 157 / 199.8Syn Z: 0.01

Background carrier burden — how many people carry a rare variant somewhere in GPD1L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

384 rare PASS variants

Rare truncating (LoF)

1 in 3,700

58 rare PASS variants

Rare synonymous (reference)

1 in 97

194 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPD1L. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 2,800
South Asian	~43k	1 in 190	1 in 2,800
Remaining (unassigned)	~30k	1 in 170	≈ 1 in 14,000
European (Finnish)	~27k	1 in 620	none seen
Admixed American	~22k	1 in 150	≈ 1 in 20,000
African / African American	~21k	1 in 240	1 in 3,000
East Asian	~20k	1 in 300	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 310	none seen
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 8 coding exons well covered in gnomAD exomes; exons 7, 8 marginal. Genomes: all 8.? see exons ↓