PGLS

protein-coding

6-phosphogluconolactonase

Gene summary

Enables 6-phosphogluconolactonase activity. Involved in pentose-phosphate shunt. Acts upstream of or within pentose-phosphate shunt, oxidative branch. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_012088.3

Inheritance

—

ClinVar variants

U:64B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr19:17,511,636-17,521,288

External References & Databases

Ensembl (ENSG00000130313)

Transcript & Mutation Effects

hg38 • Region Span ~9.7 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 PGLS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 59

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012088.3. 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			1 clinvar	3 clinvar		4
missense			62 clinvar	1 clinvar	2 clinvar	65
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	64	4	2	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012088.3	RefSeq	NP_036220.1	5	MANE Select
ENST00000252603.7	Ensembl	ENSP00000252603.1	5	MANE Select
ENST00000594761.5	Ensembl	ENSP00000471446.1	4	Standard
ENST00000595782.1	Ensembl	ENSP00000471951.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pentose phosphate pathway - Homo sapiens (human)
Pentose Phosphate Pathway (Erythrocyte)
Warburg Effect
Pentose Phosphate Pathway
Glucose-6-phosphate dehydrogenase deficiency

Biological Process

carbohydrate metabolic process
pentose-phosphate shunt
pentose-phosphate shunt, oxidative branch

Molecular Function

protein binding
6-phosphogluconolactonase activity

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252603
Coding exons: 5
Length: 9660
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125743
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.207	126	133	0.949	0.00000764	1565
Missense (PolyPhen)		38	47.119	0.80647		563
Synonymous	-0.0383	65	64.6	1.01	0.00000429	568
Loss of Function	1.04	6	9.44	0.636	5.02e-7	103

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000099	0.000097	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolysis of 6-phosphogluconolactone to 6- phosphogluconate.;

Recessive Scores

pRec: 0.220

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.992

Gene Damage Prediction

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