GPD2

Chr 2AD

glycerol-3-phosphate dehydrogenase 2

Also known as: GDH2, GPDM, mGDH, mGPDH

NCBI Gene: 2820 ENSG00000115159 UniProt: P43304 OMIM: 138430

The protein encoded by this gene localizes to the inner mitochondrial membrane and catalyzes the conversion of glycerol-3-phosphate to dihydroxyacetone phosphate, using FAD as a cofactor. Along with GDP1, the encoded protein constitutes the glycerol phosphate shuttle, which reoxidizes NADH formed during glycolysis. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Jan 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Type 2 diabetes mellitus, susceptibility to}MIM #125853

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.000

Z-score 2.23

OE 0.60 (0.43–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.72Z-score

OE missense 0.90 (0.82–0.98)

361 obs / 401.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.43–0.86)

0≤0.351.4

Missense OE?0.90 (0.82–0.98)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 22 / 36.5Missense obs/exp: 361 / 401.9Syn Z: -0.71

Background carrier burden — how many people carry a rare variant somewhere in GPD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

816 rare PASS variants

Rare truncating (LoF)

1 in 1,200

149 rare PASS variants

Rare synonymous (reference)

1 in 190

303 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPD2. 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 97	1 in 1,100
South Asian	~43k	1 in 97	1 in 530
Remaining (unassigned)	~30k	1 in 79	1 in 400
European (Finnish)	~27k	1 in 290	1 in 1,800
Admixed American	~22k	1 in 71	1 in 890
African / African American	~21k	1 in 64	1 in 820
East Asian	~20k	1 in 92	1 in 750
Ashkenazi Jewish	~13k	1 in 270	1 in 870
Middle Eastern	~2,884	1 in 87	1 in 570

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 16 coding exons well covered in gnomAD exomes; exons 2, 5, 9, 14, 15, 16 marginal. Genomes: all 16.? see exons ↓