GLUD2

protein-coding

glutamate dehydrogenase 2

Gene summary

The protein encoded by this gene is localized to the mitochondrion and acts as a homohexamer to recycle glutamate during neurotransmission. The encoded enzyme catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate. This gene is intronless.[provided by RefSeq, Jan 2010]

Previous symbols:

GLUDP1

MANE transcript

NM_012084.4

Inheritance

—

ClinVar variants

P:1U:64B:9

Top phenotype

Parkinson disease, late-onset

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chrX:121,047,610-121,050,094

External References & Databases

Ensembl (ENSG00000182890)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GLUD2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 9

Parkinson disease, late-onsetTotal: 1

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012084.4. 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				3 clinvar	1 clinvar	4
missense			64 clinvar	4 clinvar	1 clinvar	69
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	64	7	2	74

Highest pathogenic variant AF is 0.0002875767

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012084.4	RefSeq	NP_036216.2	1	MANE Select
ENST00000328078.3	Ensembl	ENSP00000327589.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alanine, aspartate and glutamate metabolism - Homo sapiens (human)
D-Glutamine and D-glutamate metabolism - Homo sapiens (human)
Proximal tubule bicarbonate reclamation - Homo sapiens (human)
Necroptosis - Homo sapiens (human)
Nitrogen metabolism - Homo sapiens (human)

Biological Process

glutamate metabolic process
glutamate biosynthetic process
glutamate catabolic process
oxidation-reduction process

Molecular Function

glutamate dehydrogenase (NAD+) activity
glutamate dehydrogenase [NAD(P)+] activity
GTP binding
ADP binding
leucine binding

Cellular Component

cytoplasm
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000328078
Coding exons: 1
Length: 2333
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.825	188	223	0.844	0.0000178	3665
Missense (PolyPhen)		40	66.994	0.59707		1149
Synonymous	-0.399	93	88.2	1.05	0.00000688	1150
Loss of Function	1.15	3	6.05	0.496	3.90e-7	145

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Important for recycling the chief excitatory neurotransmitter, glutamate, during neurotransmission.;

Recessive Scores

pRec: 0.620

Intolerance Scores

LoFtool: 0.0904
RVIS EVS: 0.15
RVIS percentile EVS: 64.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.961

Gene Damage Prediction

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