PGK1

phosphoglycerate kinase 1

Basic information

Region (hg38): X:77910738-78129295

Links

ENSG00000102144 ∙ NCBI:5230 ∙ OMIM:311800 ∙ HGNC:8896 ∙ Uniprot:P00558 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease due to phosphoglycerate kinase 1 deficiency (Definitive), mode of inheritance: XLR
• glycogen storage disease due to phosphoglycerate kinase 1 deficiency (Strong), mode of inheritance: XL
• glycogen storage disease due to phosphoglycerate kinase 1 deficiency (Strong), mode of inheritance: XL
• glycogen storage disease due to phosphoglycerate kinase 1 deficiency (Supportive), mode of inheritance: XL
• glycogen storage disease due to phosphoglycerate kinase 1 deficiency (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Phosphoglycerate kinase 1 deficiency	XL	Hematologic; Musculoskeletal; Renal	Individuals (males by report) may have partially transfusion-dependent anemia, as well as hemolytic crises requiring measures such as exchange transfusion; Rhabdomyolysis leading to acute renal failure has also been reported, and	Hematologic; Musculoskeletal; Neurologic; Renal	5764452; 6933565; 7082849; 3605066; 2715616; 1547346; 7577653; 9512313; 16412025; 16567715; 17222195; 22705348

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PGK1 gene.

• not provided (447 variants)
• Menkes kinky-hair syndrome;Cutis laxa, X-linked;X-linked distal spinal muscular atrophy type 3 (267 variants)
• Menkes kinky-hair syndrome;X-linked distal spinal muscular atrophy type 3;Cutis laxa, X-linked (256 variants)
• X-linked distal spinal muscular atrophy type 3;Menkes kinky-hair syndrome;Cutis laxa, X-linked (238 variants)
• Menkes kinky-hair syndrome (236 variants)
• Cutis laxa, X-linked;Menkes kinky-hair syndrome;X-linked distal spinal muscular atrophy type 3 (162 variants)
• Inborn genetic diseases (158 variants)
• Cutis laxa, X-linked;X-linked distal spinal muscular atrophy type 3;Menkes kinky-hair syndrome (79 variants)
• X-linked distal spinal muscular atrophy type 3;Cutis laxa, X-linked;Menkes kinky-hair syndrome (68 variants)
• not specified (67 variants)
• Glycogen storage disease due to phosphoglycerate kinase 1 deficiency (46 variants)
• Ehlers-Danlos syndrome (26 variants)
• X-linked distal spinal muscular atrophy type 3 (20 variants)
• Cutis laxa, X-linked (20 variants)
• ATP7A-related condition (7 variants)
• PGK1-related condition (4 variants)
• See cases (3 variants)
• Intellectual disability (2 variants)
• History of neurodevelopmental disorder (2 variants)
• PGK1-Related Disorder (1 variants)
• ATP7A-realted disorder (1 variants)
• Charcot-Marie-Tooth disease (1 variants)
• Au-Kline syndrome (1 variants)
• Profound global developmental delay;Epileptic encephalopathy (1 variants)
• Charcot-Marie-Tooth disease type 2 (1 variants)
• Menkes kinky-hair syndrome;Cutis laxa, X-linked (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PGK1 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				25	3	28
missense		3	85	8	7	103
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region		1	4	4	4	13
non coding	117	100	415	573	99	1304
Total	117	103	501	606	109

Variants in PGK1

This is a list of pathogenic ClinVar variants found in the PGK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-77910803-T-C		not specified	Uncertain significance (Feb 08, 2013)
X-77910848-T-C		not specified	Likely benign (Jan 17, 2017)
X-77910848-T-G		not specified	Likely benign (Jan 11, 2017)
X-77910952-T-C			Benign (Jun 20, 2018)
X-77968926-G-A		not specified	Uncertain significance (May 30, 2023)
X-77968990-C-T		not specified	Conflicting classifications of pathogenicity (Apr 27, 2022)
X-77969089-C-T		not specified	Uncertain significance (Jul 07, 2022)
X-77969227-T-C		not specified	Uncertain significance (Apr 27, 2023)
X-77969275-G-A		not specified	Uncertain significance (Sep 25, 2023)
X-77969353-T-C		not specified	Uncertain significance (Aug 17, 2022)
X-77969382-C-T		Menkes kinky-hair syndrome	Benign (May 28, 2019)
X-77969383-G-T		not specified	Uncertain significance (Jan 25, 2023)
X-77969410-T-A		not specified	Uncertain significance (Nov 21, 2022)
X-77969470-T-C		not specified	Uncertain significance (Jan 24, 2023)
X-77969516-G-A			Likely benign (Feb 01, 2023)
X-77969598-C-T		not specified	Uncertain significance (Jan 24, 2024)
X-77969611-G-A		not specified	Uncertain significance (Sep 14, 2022)
X-77971632-G-C		ATP7A-related disorder	Likely benign (Jan 17, 2024)
X-77971647-T-C		Menkes kinky-hair syndrome;X-linked distal spinal muscular atrophy type 3;Cutis laxa, X-linked	Likely benign (Dec 27, 2023)
X-77971649-C-G		X-linked distal spinal muscular atrophy type 3;Menkes kinky-hair syndrome;Cutis laxa, X-linked	Likely benign (Nov 18, 2023)
X-77971655-T-C		Menkes kinky-hair syndrome;Cutis laxa, X-linked;X-linked distal spinal muscular atrophy type 3	Uncertain significance (Feb 02, 2023)
X-77971656-G-A		Cutis laxa, X-linked;Menkes kinky-hair syndrome;X-linked distal spinal muscular atrophy type 3 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Sep 10, 2023)
X-77971658-G-A		Cutis laxa, X-linked;Menkes kinky-hair syndrome;X-linked distal spinal muscular atrophy type 3	Uncertain significance (May 21, 2019)
X-77971660-G-A		Menkes kinky-hair syndrome;Cutis laxa, X-linked;X-linked distal spinal muscular atrophy type 3	Likely benign (Oct 22, 2023)
X-77971662-G-C		X-linked distal spinal muscular atrophy type 3;Cutis laxa, X-linked;Menkes kinky-hair syndrome	Likely benign (Jun 13, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PGK1	protein_coding	protein_coding	ENST00000373316	11	64109

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.765	0.234	125715	0	3	125718	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.338	144	156	0.924	0.0000110	2752
Missense in Polyphen		33	50.393	0.65485		1011
Synonymous	0.0294	57	57.3	0.995	0.00000395	826
Loss of Function	2.91	2	13.5	0.148	0.00000100	241

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000245	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000524	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). May play a role in sperm motility (PubMed:26677959). {ECO:0000269|PubMed:2324090, ECO:0000269|PubMed:26677959}.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics;Abacavir Pathway, Pharmacokinetics/Pharmacodynamics;Warburg Effect;Lamivudine Metabolism Pathway;Cori Cycle;Photodynamic therapy-induced HIF-1 survival signaling;Pathways in clear cell renal cell carcinoma;Glycolysis and Gluconeogenesis;Metabolism of carbohydrates;Glycolysis Gluconeogenesis;HIF-2-alpha transcription factor network;Metabolism;Glycolysis;gluconeogenesis;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Gluconeogenesis;Glucose metabolism;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

• pRec: 0.973

Intolerance Scores

• rvis_EVS: -0.45
• rvis_percentile_EVS: 24

Haploinsufficiency Scores

• pHI: 0.801
• hipred: Y
• hipred_score: 0.546
• ghis: 0.521

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.932

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pgk1

Zebrafish Information Network

• Gene name: pgk1
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: swollen

Gene ontology

• Biological process: gluconeogenesis;glycolytic process;phosphorylation;negative regulation of angiogenesis;epithelial cell differentiation;plasminogen activation;canonical glycolysis;cellular response to hypoxia;positive regulation of oxidative phosphorylation
• Cellular component: extracellular space;cytosol;membrane;membrane raft;extracellular exosome
• Molecular function: phosphoglycerate kinase activity;protein binding;ATP binding;ADP binding;protein-disulfide reductase activity