H6PD

hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase

Basic information

Region (hg38): 1:9234773-9271337

Previous symbols: [ "GDH" ]

Links

ENSG00000049239 ∙ NCBI:9563 ∙ OMIM:138090 ∙ HGNC:4795 ∙ Uniprot:O95479 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cortisone reductase deficiency 1 (Moderate), mode of inheritance: AR
• cortisone reductase deficiency (Supportive), mode of inheritance: AD
• cortisone reductase deficiency 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cortisone reductase deficiency	AR	General	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	Endocrine	10522997; 12858176; 15827106; 18628520

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the H6PD gene.

• not provided (127 variants)
• Inborn genetic diseases (55 variants)
• Cortisone reductase deficiency 1 (12 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the H6PD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				27	20	47
missense			80	16	10	106
nonsense	1					1
start loss						0
frameshift			2		1	3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	4	5
non coding			1	3	1	5
Total	1	0	83	46	32

Highest pathogenic variant AF is 0.0000854

Variants in H6PD

This is a list of pathogenic ClinVar variants found in the H6PD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-9244919-CCCCAGGCA-C		not specified • Cortisone reductase deficiency 1	Benign (Apr 11, 2023)
1-9244965-T-G		Inborn genetic diseases	Likely benign (May 11, 2022)
1-9245014-C-T			Uncertain significance (Oct 05, 2022)
1-9245061-T-C		Inborn genetic diseases	Uncertain significance (May 09, 2023)
1-9245120-C-T			Benign (Dec 07, 2023)
1-9245143-C-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
1-9245151-G-C			Uncertain significance (Aug 17, 2023)
1-9245189-C-T			Benign (Dec 22, 2023)
1-9245236-A-C		Inborn genetic diseases	Uncertain significance (Jun 01, 2022)
1-9245250-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 16, 2024)
1-9245257-AC-A		Cortisone reductase deficiency 1	Pathogenic (Oct 01, 2008)
1-9245260-G-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
1-9245276-C-T			Benign (Jan 18, 2024)
1-9245277-G-A			Uncertain significance (Aug 20, 2022)
1-9245301-G-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
1-9245304-A-G		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
1-9245334-C-T			Benign (Jan 06, 2024)
1-9245349-A-G			Uncertain significance (Oct 17, 2022)
1-9245356-A-G		Inborn genetic diseases	Uncertain significance (Aug 17, 2023)
1-9245386-A-C			Benign (Jan 25, 2024)
1-9245450-T-C			Likely benign (Jul 31, 2018)
1-9245452-A-G		Inborn genetic diseases	Uncertain significance (Nov 16, 2022)
1-9245473-A-G			Likely benign (Jul 17, 2021)
1-9246952-TC-T			Benign (Dec 14, 2022)
1-9246952-T-TC			Benign (May 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
H6PD	protein_coding	protein_coding	ENST00000377403	4	36563

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.59e-9	0.908	125642	0	106	125748	0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.13	549	479	1.15	0.0000343	5139
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000631	0.000624
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.000328	0.000326
Finnish	0.000565	0.000554
European (Non-Finnish)	0.000423	0.000413
Middle Eastern	0.000328	0.000326
South Asian	0.000459	0.000457
Other	0.00148	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Oxidizes glucose-6-phosphate and glucose, as well as other hexose-6-phosphates.
• Pathway: Pentose phosphate pathway - Homo sapiens (human);pentose phosphate pathway (oxidative branch);Pentose phosphate cycle;pentose phosphate pathway;Pentose phosphate pathway (Consensus)

Intolerance Scores

• loftool: 0.0874
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.19

Haploinsufficiency Scores

• pHI: 0.154
• hipred: N
• hipred_score: 0.331
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.733

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: H6pd
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: glucose metabolic process;pentose-phosphate shunt;oxidation-reduction process
• Cellular component: endoplasmic reticulum lumen
• Molecular function: glucose-6-phosphate dehydrogenase activity;6-phosphogluconolactonase activity;glucose 1-dehydrogenase [NAD(P)] activity;NADP binding