PFKP

protein-coding

phosphofructokinase, platelet

Gene summary

This gene encodes a member of the phosphofructokinase A protein family. The encoded enzyme is the platelet-specific isoform of phosphofructokinase and plays a key role in glycolysis regulation. This gene may play a role in metabolic reprogramming in some cancers, including clear cell renal cell carcinomas, and cancer of the bladder, breast, and lung. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

MANE transcript

NM_002627.5

Inheritance

—

ClinVar variants

U:157B:34

Top phenotype

PFKP-related disorder

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr10:3,066,333-3,137,718

External References & Databases

Ensembl (ENSG00000067057)

Transcript & Mutation Effects

hg38 • Region Span ~71.4 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 PFKP variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 144

not providedTotal: 24

PFKP-related disorderTotal: 6

Anophthalmia-microphthalmia syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002627.5. 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			3 clinvar	13 clinvar	15 clinvar	31
missense			140 clinvar	5 clinvar		145
nonsense			1 clinvar			1
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			13 clinvar			13
Total	0	0	157	19	15	191

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002627.5	RefSeq	NP_002618.1	22	MANE Select
ENST00000381125.9	Ensembl	ENSP00000370517.4	22	MANE Select
NM_001242339.2	RefSeq	NP_001229268.1	23	Standard
NM_001323067.2	RefSeq	NP_001309996.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

fructose 6-phosphate metabolic process
glucose catabolic process
fructose 1,6-bisphosphate metabolic process
canonical glycolysis
cellular response to leukemia inhibitory factor

Molecular Function

6-phosphofructokinase activity
ATP binding
AMP binding
protein-containing complex binding
cadherin binding

Cellular Component

nucleus
cytoplasm
cytosol
6-phosphofructokinase complex
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381125
Coding exons: 22
Length: 71380
Individuals with no LoFs: 125553
Homozygous LoFs: 1
Heterozygous LoFs: 193
Defined: 125747
p: 0.000772

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.00709	521	521	1.00	0.0000350	5109
Missense (PolyPhen)		177	215.27	0.82221		1944
Synonymous	-5.01	309	215	1.43	0.0000166	1516
Loss of Function	0.711	40	45.2	0.886	0.00000244	476

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0027	0.0026	notable
Latino/Admixed American	0.00052	0.00052	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00077	0.00076	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00063	0.00062	rare
South Asian	0.0012	0.0011	notable
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.313

Intolerance Scores

LoFtool: 0.567
RVIS EVS: -2.63
RVIS percentile EVS: 0.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.937

Gene Damage Prediction

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