H6PD

protein-coding

hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase

Gene summary

There are 2 forms of glucose-6-phosphate dehydrogenase. G form is X-linked and H form, encoded by this gene, is autosomally linked. This H form shows activity with other hexose-6-phosphates, especially galactose-6-phosphate, whereas the G form is specific for glucose-6-phosphate. Both forms are present in most tissues, but H form is not found in red cells. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_004285.4

Inheritance

AR, AD

ClinVar variants

P:9U:184B:108

Top phenotype

Cortisone reductase deficiency

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr1:9,234,774-9,271,337

External References & Databases

Ensembl (ENSG00000049239)

Transcript & Mutation Effects

hg38 • Region Span ~36.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cortisone reductase deficiency 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011503

Submitter: Ambry Genetics

cortisone reductase deficiencySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000193

Submitter: Orphanet

cortisone reductase deficiency 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011503

Submitter: Labcorp Genetics (formerly Invitae)

cortisone reductase deficiency 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011503

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Cortisone reductase deficiencyAR

Manifestation: Endocrine

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 10522997; 12858176; 15827106; 18628520

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to H6PD variants in ClinVar

5 Conditions Cataloged

not providedTotal: 170

Inborn genetic diseasesTotal: 163

Cortisone reductase deficiency 1Total: 17

not specifiedTotal: 9

H6PD-related disorderTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004285.4. 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	1 clinvar			54 clinvar	16 clinvar	71
missense	1 clinvar		181 clinvar	30 clinvar	8 clinvar	220
nonsense	3 clinvar	1 clinvar				4
start loss						0
frameshift	2 clinvar	1 clinvar	2 clinvar			5
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	7	2	184	84	24	301

Highest pathogenic variant AF is 0.000084877334

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004285.4	RefSeq	NP_004276.2	4	MANE Select
ENST00000377403.7	Ensembl	ENSP00000366620.2	4	MANE Select
NM_001282587.2	RefSeq	NP_001269516.1	5	Standard
ENST00000602477.1	Ensembl	ENSP00000473348.1	5	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 (oxidative branch)
Pentose phosphate cycle
pentose phosphate pathway
Pentose phosphate pathway

Biological Process

glucose metabolic process
pentose-phosphate shunt
oxidation-reduction process

Molecular Function

glucose-6-phosphate dehydrogenase activity
6-phosphogluconolactonase activity
glucose 1-dehydrogenase [NAD(P)] activity
NADP binding

Cellular Component

endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377403
Coding exons: 4
Length: 36563
Individuals with no LoFs: 125642
Homozygous LoFs: 0
Heterozygous LoFs: 106
Defined: 125748
p: 0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.13	549	479	1.15	0.0000343	5139
Missense (PolyPhen)		183	159.66	1.1462		1748
Synonymous	-1.74	247	215	1.15	0.0000156	1640
Loss of Function	1.80	17	27.1	0.627	0.00000146	275

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00056	0.00055	rare
European (Non-Finnish)	0.00042	0.00041	rare
South Asian	0.00046	0.00046	rare
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Oxidizes glucose-6-phosphate and glucose, as well as other hexose-6-phosphates.;

Intolerance Scores

LoFtool: 0.0874
RVIS EVS: -0.89
RVIS percentile EVS: 10.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.733

Gene Damage Prediction

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