PFKM

phosphofructokinase, muscle, the group of Protein phosphatase 1 regulatory subunits|MicroRNA protein coding host genes

Basic information

Region (hg38): 12:48105139-48146404

Previous symbols: [ "PFKX" ]

Links

ENSG00000152556 ∙ NCBI:5213 ∙ OMIM:610681 ∙ HGNC:8877 ∙ Uniprot:P08237 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycogen storage disease VII (Strong), mode of inheritance: AR
• glycogen storage disease VII (Definitive), mode of inheritance: AR
• glycogen storage disease VII (Strong), mode of inheritance: AR
• glycogen storage disease VII (Strong), mode of inheritance: AR
• glycogen storage disease VII (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycogen storage disease VII	AR	Cardiovascular; Musculoskeletal; Renal	There is a wide range of types and severity, but avoidance of excessive exercise may be beneficial in order to avoid renal sequale; Surveillance for cardiovascular complications (eg, cardiac hypertrophy) may allow early detection and treatment	Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic; Renal	14339001; 4228297; 4228753; 4258222; 6444532; 6444721; 6943439; 6220601; 2945125; 2960695; 2140573; 1533013; 8444874; 8037209; 7513946; 7550225; 7479776; 8889589; 9389749; 22133655; 22364848

ClinVar

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

• Glycogen storage disease, type VII (27 variants)
• not provided (1 variants)
• Glycogen storage disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PFKM 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			1	294	5	300
missense		5	141	3	3	152
nonsense	6	17				23
start loss			1			1
frameshift	20	32	1			53
inframe indel						0
splice donor/acceptor (+/-2bp)	1	29		1		31
splice region			8	70	3	81
non coding		2	21	190	45	258
Total	27	85	165	488	53

Highest pathogenic variant AF is 0.0000460

Variants in PFKM

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

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

Position	Type	Phenotype	Significance	ClinVar
12-48106115-C-T			Likely benign (Jun 29, 2018)
12-48106148-A-T			Benign (Jun 23, 2018)
12-48107081-C-G			Benign (Jun 19, 2018)
12-48107084-A-T			Likely benign (May 18, 2019)
12-48107374-A-G		Glycogen storage disease, type VII	Uncertain significance (Mar 09, 2021)
12-48107378-A-T		Glycogen storage disease, type VII	Benign (Nov 30, 2023)
12-48107385-C-T		Glycogen storage disease, type VII	Likely benign (Nov 23, 2022)
12-48107426-G-T		Glycogen storage disease, type VII	Uncertain significance (Jul 14, 2021)
12-48107434-G-A			Uncertain significance (Jul 11, 2019)
12-48107628-A-G			Benign (Jun 14, 2018)
12-48108169-G-T		PFKM-related disorder	Likely benign (Aug 04, 2021)
12-48108204-G-A		PFKM-related disorder	Likely benign (Nov 25, 2019)
12-48108249-A-C			Likely benign (Aug 15, 2018)
12-48108317-A-G			Benign (Jun 16, 2018)
12-48108360-G-A			Likely benign (Sep 07, 2019)
12-48118478-C-T			Likely benign (Jul 01, 2023)
12-48118502-C-A		Glycogen storage disease, type VII	Benign (Sep 05, 2021)
12-48118561-A-G			Likely benign (May 01, 2022)
12-48119238-G-C		Glycogen storage disease, type VII	Uncertain significance (Dec 21, 2022)
12-48119239-C-T		Glycogen storage disease, type VII	Uncertain significance (Jun 14, 2016)
12-48119241-G-A		Glycogen storage disease, type VII	Uncertain significance (Jun 14, 2016)
12-48119244-C-A		Glycogen storage disease, type VII	Benign/Likely benign (Jul 12, 2019)
12-48119303-T-G		Glycogen storage disease, type VII	Benign (Jun 29, 2018)
12-48119350-C-A			Uncertain significance (Dec 15, 2020)
12-48119351-C-T		Glycogen storage disease, type VII	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PFKM	protein_coding	protein_coding	ENST00000340802	24	41266

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.76e-18	0.412	125612	0	136	125748	0.000541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.36	334	479	0.697	0.0000285	5598
Missense in Polyphen		107	190.53	0.56158		2254
Synonymous	1.14	153	172	0.890	0.00000999	1673
Loss of Function	1.71	34	46.6	0.730	0.00000273	514

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000427	0.000427
Ashkenazi Jewish	0.00466	0.00467
East Asian	0.000435	0.000435
Finnish	0.000647	0.000647
European (Non-Finnish)	0.000434	0.000413
Middle Eastern	0.000435	0.000435
South Asian	0.000196	0.000196
Other	0.000978	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
• Disease: DISEASE: Glycogen storage disease 7 (GSD7) [MIM:232800]: A metabolic disorder characterized by exercise intolerance with associated nausea and vomiting, muscle cramping, exertional myopathy and compensated hemolysis. Short bursts of intense activity are particularly difficult. Severe muscle cramps and myoglobinuria develop after vigorous exercise. {ECO:0000269|PubMed:22133655, ECO:0000269|PubMed:24427140, ECO:0000269|PubMed:7513946, ECO:0000269|PubMed:7825568, ECO:0000269|PubMed:8889589}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);Fructose and mannose metabolism - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);RNA degradation - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Pentose phosphate pathway - Homo sapiens (human);Glycolysis;Glycogenosis, Type VII. Tarui disease;Fanconi-bickel syndrome;Pathways in clear cell renal cell carcinoma;Insulin Signaling;Glycolysis and Gluconeogenesis;phosphoinositides and their downstream targets;Metabolism of carbohydrates;Glycolysis Gluconeogenesis;Glycolysis and Gluconeogenesis;Metabolism;Pentose phosphate cycle;Glycolysis;Galactose metabolism;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Glucose metabolism;Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

• pRec: 0.784

Intolerance Scores

• loftool: 0.291
• rvis_EVS: -0.46
• rvis_percentile_EVS: 23.57

Haploinsufficiency Scores

• pHI: 0.259
• hipred: Y
• hipred_score: 0.637
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pfkm
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); immune system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; muscle phenotype

Gene ontology

• Biological process: glycogen catabolic process;fructose 6-phosphate metabolic process;glucose catabolic process;glycolytic process;fructose 1,6-bisphosphate metabolic process;positive regulation of insulin secretion;glucose homeostasis;positive regulation of transcription by RNA polymerase II;muscle cell cellular homeostasis;carbohydrate phosphorylation;protein complex oligomerization;glycolytic process through fructose-6-phosphate;canonical glycolysis;glycolysis from storage polysaccharide through glucose-1-phosphate
• Cellular component: nucleus;cytosol;6-phosphofructokinase complex;apical plasma membrane;sperm principal piece
• Molecular function: 6-phosphofructokinase activity;protein binding;ATP binding;protein C-terminus binding;AMP binding;kinase binding;identical protein binding;protein homodimerization activity;metal ion binding;monosaccharide binding;fructose binding;fructose-6-phosphate binding