PGAM5

PGAM family member 5, mitochondrial serine/threonine protein phosphatase, the group of Phosphoglycerate mutases|Serine/threonine phosphatases

Basic information

Region (hg38): 12:132710819-132722734

Links

ENSG00000247077 ∙ NCBI:192111 ∙ OMIM:614939 ∙ HGNC:28763 ∙ Uniprot:Q96HS1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PGAM5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PGAM5 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	3	4
missense			26		3	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					21	21
Total	0	0	26	1	27

Variants in PGAM5

This is a list of pathogenic ClinVar variants found in the PGAM5 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-132710832-T-C			Benign (Jun 19, 2021)
12-132710873-C-T			Benign (Nov 12, 2018)
12-132710880-G-T		not specified	Uncertain significance (Sep 16, 2021)
12-132710893-C-T		not specified	Uncertain significance (Dec 03, 2021)
12-132710937-G-A		not specified	Uncertain significance (Sep 22, 2023)
12-132710937-G-C		not specified	Uncertain significance (Dec 16, 2021)
12-132710956-C-G		not specified	Uncertain significance (Nov 27, 2023)
12-132710970-C-T		not specified	Uncertain significance (Aug 10, 2021)
12-132711034-C-T		not specified	Uncertain significance (Sep 17, 2021)
12-132711040-C-G		not specified	Uncertain significance (Aug 30, 2022)
12-132711135-A-G			Benign (Nov 12, 2018)
12-132711244-G-A			Benign (Jun 20, 2021)
12-132711321-C-T			Benign (Jun 19, 2021)
12-132714863-A-G		not specified	Uncertain significance (Oct 12, 2021)
12-132714881-A-G		not specified	Uncertain significance (Jul 25, 2023)
12-132714886-C-T		not specified	Uncertain significance (Nov 17, 2022)
12-132714896-A-G		not specified	Uncertain significance (Jun 22, 2023)
12-132714908-G-A		not specified	Uncertain significance (Oct 20, 2024)
12-132714934-G-C		not specified	Uncertain significance (Nov 15, 2021)
12-132714938-A-G		not specified	Uncertain significance (Jun 29, 2023)
12-132715004-C-T		not specified	Uncertain significance (Jul 05, 2023)
12-132715009-G-C		not specified	Uncertain significance (Jun 26, 2024)
12-132715018-C-T		not specified	Uncertain significance (Jul 27, 2022)
12-132715093-A-ATCC			Benign (Jun 20, 2021)
12-132715293-G-A			Benign (Nov 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PGAM5	protein_coding	protein_coding	ENST00000498926	6	11824

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000641	0.735	125466	0	23	125489	0.0000916

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.964	128	163	0.787	0.0000117	1836
Missense in Polyphen		33	55.608	0.59344		570
Synonymous	-1.31	85	70.9	1.20	0.00000541	616
Loss of Function	1.03	8	11.8	0.676	7.69e-7	134

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000289	0.000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000266	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2- dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore. {ECO:0000269|PubMed:18387606, ECO:0000269|PubMed:19590015, ECO:0000269|PubMed:22265414}.
• Pathway: TNF signaling pathway - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Necroptosis - Homo sapiens (human);Receptor Mediated Mitophagy;Mitophagy (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.274
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.76

Haploinsufficiency Scores

• pHI: 0.364
• hipred: Y
• hipred_score: 0.612
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.788

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pgam5
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton 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

Gene ontology

• Biological process: protein dephosphorylation;macroautophagy;positive regulation of GTPase activity;necroptotic process;negative regulation of cold-induced thermogenesis
• Cellular component: mitochondrion;mitochondrial outer membrane;integral component of membrane
• Molecular function: protein serine/threonine phosphatase activity;GTPase activator activity;protein binding;phosphatase activity;protein-containing complex binding