GFM1

G elongation factor mitochondrial 1

Basic information

Region (hg38): 3:158644526-158695581

Links

ENSG00000168827 ∙ NCBI:85476 ∙ OMIM:606639 ∙ HGNC:13780 ∙ Uniprot:Q96RP9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (Definitive), mode of inheritance: AR
• hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (Supportive), mode of inheritance: AR
• hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (Strong), 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 1	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	Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	15537906; 17160893; 21119709

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GFM1 gene.

• not provided (576 variants)
• Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 (212 variants)
• not specified (34 variants)
• Inborn genetic diseases (27 variants)
• GFM1-related condition (6 variants)
• Combined oxidative phosphorylation deficiency (5 variants)
• See cases (4 variants)
• - (2 variants)
• Severe muscular hypotonia;Developmental regression;Relative macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GFM1 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			2	182	3	187
missense	3	12	98	14	3	130
nonsense	17	19				36
start loss	1					1
frameshift	35	31	1			67
inframe indel	1					1
splice donor/acceptor (+/-2bp)	1	29	1		1	32
splice region			5	41	5	51
non coding		1	20	88	46	155
Total	58	92	122	284	53

Highest pathogenic variant AF is 0.0000329

Variants in GFM1

This is a list of pathogenic ClinVar variants found in the GFM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-158644550-C-T		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Uncertain significance (Jan 12, 2018)
3-158644562-C-T		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Likely benign (Apr 27, 2017)
3-158644569-C-G		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Uncertain significance (Jan 12, 2018)
3-158644597-C-T		not specified • Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 • GFM1-related disorder	Conflicting classifications of pathogenicity (Oct 25, 2021)
3-158644602-C-T		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Benign (Jul 10, 2021)
3-158644604-A-G		not specified • Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Benign (Jan 12, 2018)
3-158644610-C-T		not specified	Likely benign (May 17, 2016)
3-158644624-C-T		not specified • Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Benign/Likely benign (Oct 08, 2021)
3-158644637-G-A		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Pathogenic (Aug 12, 2013)
3-158644646-G-C			Likely benign (May 22, 2023)
3-158644650-G-C			Uncertain significance (Sep 15, 2014)
3-158644652-T-C		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 • not specified	Benign (Feb 01, 2024)
3-158644652-T-G			Likely benign (Jan 19, 2023)
3-158644655-A-G			Likely benign (Jul 08, 2021)
3-158644661-C-T			Likely benign (Oct 30, 2023)
3-158644662-G-T			Uncertain significance (Feb 17, 2023)
3-158644664-G-A			Likely benign (May 05, 2023)
3-158644670-G-C			Likely benign (Oct 31, 2021)
3-158644673-G-A			Likely benign (Oct 30, 2020)
3-158644683-GC-G		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Pathogenic/Likely pathogenic (Mar 16, 2022)
3-158644685-C-T		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1	Likely benign (Oct 09, 2023)
3-158644687-C-T			Uncertain significance (Apr 19, 2022)
3-158644688-C-A			Likely benign (Dec 17, 2021)
3-158644688-C-T			Likely benign (Jul 07, 2023)
3-158644690-C-T		Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 • GFM1-related disorder	Conflicting classifications of pathogenicity (Jan 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GFM1	protein_coding	protein_coding	ENST00000486715	18	48298

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.28e-13	0.993	125646	0	102	125748	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.28	339	412	0.823	0.0000213	4879
Missense in Polyphen		109	151.17	0.72104		1725
Synonymous	-0.609	151	142	1.07	0.00000713	1461
Loss of Function	2.65	27	46.5	0.580	0.00000298	493

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000735	0.000731
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.000463	0.000462
European (Non-Finnish)	0.000449	0.000448
Middle Eastern	0.000272	0.000272
South Asian	0.000588	0.000588
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A- site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. Does not mediate the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis. {ECO:0000255|HAMAP-Rule:MF_03061, ECO:0000269|PubMed:19716793}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 1 (COXPD1) [MIM:609060]: A mitochondrial disease resulting in early rapidly progressive hepatoencephalopathy. {ECO:0000269|PubMed:15537906, ECO:0000269|PubMed:17160893, ECO:0000269|PubMed:21119709, ECO:0000269|PubMed:26741492}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Translation;Metabolism of proteins;Purine metabolism;Mitochondrial translation elongation;Mitochondrial translation (Consensus)

Recessive Scores

• pRec: 0.162

Intolerance Scores

• loftool: 0.836
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.47

Haploinsufficiency Scores

• pHI: 0.0969
• hipred: N
• hipred_score: 0.463
• ghis: 0.533

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.408

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gfm1
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

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