PYGB

protein-coding

glycogen phosphorylase B, the group of Glycogen phosphorylases

Gene summary

The protein encoded by this gene is a glycogen phosphorylase found predominantly in the brain. The encoded protein forms homodimers which can associate into homotetramers, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by ATP, ADP, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in glycogen degradation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002862.4

Inheritance

—

ClinVar variants

U:172B:9

Top phenotype

ABHD12-related disorder

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr20:25,248,085-25,298,012

External References & Databases

Ensembl (ENSG00000100994)

Transcript & Mutation Effects

hg38 • Region Span ~49.9 kb

Loading mutation effect viewer...

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 PYGB variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 152

not providedTotal: 12

ABHD12-related disorderTotal: 2

Short statureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002862.4. 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			7 clinvar	3 clinvar	2 clinvar	12
missense			157 clinvar	3 clinvar	1 clinvar	161
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	172	6	3	181

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002862.4	RefSeq	NP_002853.2	20	MANE Select
ENST00000216962.9	Ensembl	ENSP00000216962.3	20	MANE Select
ENST00000428458.1	Ensembl	ENSP00000395451.1	6	Standard
ENST00000896648.1	Ensembl	ENSP00000566707.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin resistance - Homo sapiens (human)
Starch and sucrose metabolism - Homo sapiens (human)
Glucagon signaling pathway - Homo sapiens (human)
Necroptosis - Homo sapiens (human)
Insulin signaling pathway - Homo sapiens (human)

Biological Process

glycogen catabolic process
neutrophil degranulation

Molecular Function

protein binding
glycogen phosphorylase activity
pyridoxal phosphate binding
linear malto-oligosaccharide phosphorylase activity
SHG alpha-glucan phosphorylase activity

Cellular Component

extracellular region
cytoplasm
membrane
azurophil granule lumen
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216962
Coding exons: 20
Length: 49946
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125748
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0473	555	552	1.01	0.0000360	5537
Missense (PolyPhen)		229	253.1	0.90478		2532
Synonymous	-1.51	272	242	1.12	0.0000174	1619
Loss of Function	2.14	29	44.4	0.653	0.00000226	494

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00083	0.00080	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00036	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Glycogen phosphorylase that regulates glycogen mobilization (PubMed:27402852). Phosphorylase is an important allosteric enzyme in carbohydrate metabolism (PubMed:3346228). Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates (PubMed:3346228). However, all known phosphorylases share catalytic and structural properties (PubMed:3346228). {ECO:0000269|PubMed:27402852, ECO:0000303|PubMed:3346228}.;

Recessive Scores

pRec: 0.449

Intolerance Scores

LoFtool: 0.0325
RVIS EVS: -1.46
RVIS percentile EVS: 3.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

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