GPD2

protein-coding

glycerol-3-phosphate dehydrogenase 2, the group of EF-hand domain containing

Gene summary

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]

MANE transcript

NM_000408.5

Inheritance

ClinVar variants

P:1U:104B:11

Top phenotype

GPD2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr2:156,435,290-156,613,735

External References & Databases

Ensembl (ENSG00000115159)

Transcript & Mutation Effects

hg38 • Region Span ~178.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

diabetes mellitus, noninsulin-dependentNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0007455

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPD2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 12

GPD2-related disorderTotal: 9

Type 2 diabetes mellitusTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000408.5. 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				6 clinvar		6
missense	1 clinvar		97 clinvar	4 clinvar	1 clinvar	103
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	0	104	10	1	116

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000408.5	RefSeq	NP_000399.3	16	MANE Select
ENST00000438166.7	Ensembl	ENSP00000409708.2	16	MANE Select
NM_001083112.3	RefSeq	NP_001076581.2	16	Standard
ENST00000310454.10	Ensembl	ENSP00000308610.5	16	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

gluconeogenesis
glycerophosphate shuttle
glycerol catabolic process
multicellular organism growth
camera-type eye development

Molecular Function

glycerol-3-phosphate dehydrogenase [NAD+] activity
glycerol-3-phosphate dehydrogenase (quinone) activity
calcium ion binding
sn-glycerol-3-phosphate:ubiquinone-8 oxidoreductase activity

Cellular Component

mitochondrion
mitochondrial inner membrane
glycerol-3-phosphate dehydrogenase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310454
Coding exons: 16
Length: 178446
Individuals with no LoFs: 125488
Homozygous LoFs: 0
Heterozygous LoFs: 260
Defined: 125748
p: 0.00103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.724	361	402	0.898	0.0000219	4748
Missense (PolyPhen)		141	166.97	0.84444		1884
Synonymous	-0.714	150	139	1.08	0.00000736	1426
Loss of Function	2.23	22	36.5	0.602	0.00000180	454

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00092	0.00092	rare
Latino/Admixed American	0.00058	0.00058	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00049	0.00049	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.0016	0.0016	notable
South Asian	0.00052	0.00052	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.514

Intolerance Scores

LoFtool: 0.356
RVIS EVS: 0.22
RVIS percentile EVS: 68.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.847

Gene Damage Prediction

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