GFM2

GTP dependent ribosome recycling factor mitochondrial 2

Basic information

Region (hg38): 5:74721205-74767147

Links

ENSG00000164347 ∙ NCBI:84340 ∙ OMIM:606544 ∙ HGNC:29682 ∙ Uniprot:Q969S9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation deficiency 39 (Moderate), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 39 (Supportive), mode of inheritance: AR
• combined oxidative phosphorylation deficiency 39 (Limited), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 39	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Musculoskeletal	22700954; 26016410; 29075935

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFM2 gene.

• not provided (246 variants)
• not specified (28 variants)
• Inborn genetic diseases (28 variants)
• Combined oxidative phosphorylation deficiency 39 (14 variants)
• Sandhoff disease (6 variants)
• Combined oxidative phosphorylation deficiency 39;Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (2 variants)
• Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1;Combined oxidative phosphorylation deficiency 39 (1 variants)
• GFM2-related condition (1 variants)
• Mitochondrial disease (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFM2 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	31	2	34
missense			109	11	7	127
nonsense		1	8			9
start loss						0
frameshift		1	6			7
inframe indel			3		1	4
splice donor/acceptor (+/-2bp)	1	2	2			5
splice region		1	2	10	3	16
non coding			1	42	30	73
Total	1	4	130	84	40

Highest pathogenic variant AF is 0.0000329

Variants in GFM2

This is a list of pathogenic ClinVar variants found in the GFM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-74721215-A-C		Sandhoff disease	Likely benign (Jan 13, 2018)
5-74721255-CTG-C		Sandhoff disease	Benign/Likely benign (Jan 15, 2024)
5-74721280-T-C		Sandhoff disease	Uncertain significance (Jan 12, 2018)
5-74721674-C-T		not specified	Benign (Jan 30, 2024)
5-74721681-G-A			Uncertain significance (Nov 02, 2023)
5-74721687-T-C			Uncertain significance (Nov 27, 2023)
5-74721698-T-C			Uncertain significance (Jan 09, 2023)
5-74721699-G-A		Sandhoff disease	Uncertain significance (Jan 06, 2017)
5-74721708-T-C		Inborn genetic diseases	Uncertain significance (Nov 28, 2023)
5-74721747-A-AG		not specified	Uncertain significance (Aug 25, 2023)
5-74721755-G-GT		Sandhoff disease	Uncertain significance (Apr 06, 2018)
5-74721764-C-T		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
5-74721765-G-A		Sandhoff disease	Uncertain significance (Nov 28, 2017)
5-74721765-G-C		not specified • GFM2-related disorder	Benign (Jan 29, 2024)
5-74721774-T-G			Uncertain significance (Feb 18, 2022)
5-74721776-G-A			Uncertain significance (Mar 13, 2023)
5-74721782-C-T			Conflicting classifications of pathogenicity (Dec 13, 2022)
5-74721789-CA-C			Benign (Jun 21, 2022)
5-74721945-G-A			Likely benign (Nov 27, 2018)
5-74721983-T-C			Likely benign (Jul 14, 2018)
5-74722252-A-AAACTT			Benign (Jun 19, 2018)
5-74722378-C-T			Uncertain significance (Nov 27, 2023)
5-74722380-A-G		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
5-74722384-T-C		Combined oxidative phosphorylation deficiency 39	Uncertain significance (May 03, 2022)
5-74722403-T-A			Uncertain significance (Aug 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFM2	protein_coding	protein_coding	ENST00000296805	20	46168

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.49e-18	0.145	125626	0	119	125745	0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.797	363	408	0.889	0.0000203	5038
Missense in Polyphen		136	167.14	0.81371		2069
Synonymous	1.77	115	142	0.811	0.00000690	1509
Loss of Function	1.35	33	42.5	0.777	0.00000232	545

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00131	0.00131
Ashkenazi Jewish	0.000104	0.0000992
East Asian	0.000441	0.000435
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000392	0.000387
Middle Eastern	0.000441	0.000435
South Asian	0.000576	0.000555
Other	0.00115	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial GTPase that mediates the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis. Acts in collaboration with MRRF. GTP hydrolysis follows the ribosome disassembly and probably occurs on the ribosome large subunit. Not involved in the GTP-dependent ribosomal translocation step during translation elongation. {ECO:0000255|HAMAP-Rule:MF_03059, ECO:0000269|PubMed:19716793}.
• Pathway: Translation;Metabolism of proteins;Purine metabolism;Mitochondrial translation termination;Mitochondrial translation (Consensus)

Intolerance Scores

• loftool: 0.990
• rvis_EVS: 1.16
• rvis_percentile_EVS: 92.59

Haploinsufficiency Scores

• pHI: 0.136
• hipred: N
• hipred_score: 0.426
• ghis: 0.535

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.875

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gfm2

Gene ontology

• Biological process: mitochondrial translation;ribosome disassembly;mitochondrial translational elongation;mitochondrial translational termination
• Cellular component: mitochondrial matrix
• Molecular function: translation elongation factor activity;GTPase activity;protein binding;GTP binding