TUFM

Tu translation elongation factor, mitochondrial, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 16:28842410-28846348

Links

ENSG00000178952 ∙ NCBI:7284 ∙ OMIM:602389 ∙ HGNC:12420 ∙ Uniprot:P49411 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 4 (Strong), mode of inheritance: AR
• combined oxidative phosphorylation defect type 4 (Strong), mode of inheritance: AR
• combined oxidative phosphorylation defect type 4 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 4	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; Gastrointestinal; Neurologic	17160893

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TUFM 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	29	1	32
missense		3	61	1		65
nonsense			1			1
start loss			1			1
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			3	8		11
non coding			18	26	9	53
Total	0	3	85	56	10

Variants in TUFM

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

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

Position	Type	Phenotype	Significance	ClinVar
16-28842414-T-A		Combined oxidative phosphorylation defect type 4	Conflicting classifications of pathogenicity (Jun 01, 2023)
16-28842458-C-G		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 12, 2018)
16-28842530-C-T		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 12, 2018)
16-28842542-A-G		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 13, 2018)
16-28842577-C-T		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 12, 2018)
16-28842605-A-C		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 13, 2018)
16-28842626-C-T		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 13, 2018)
16-28842675-A-C		Combined oxidative phosphorylation defect type 4	Benign (Jun 14, 2018)
16-28842705-G-A		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 13, 2018)
16-28842746-C-T		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 13, 2018)
16-28842826-C-G		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 12, 2018)
16-28842865-T-C		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 12, 2018)
16-28842915-A-C		Combined oxidative phosphorylation defect type 4	Uncertain significance (Apr 27, 2017)
16-28842938-C-T		Combined oxidative phosphorylation defect type 4	Uncertain significance (Jan 12, 2018)
16-28842951-G-A		Combined oxidative phosphorylation defect type 4	Benign (Jul 15, 2018)
16-28842979-C-T			Uncertain significance (Jul 12, 2022)
16-28842985-T-A			Uncertain significance (Jan 02, 2022)
16-28842990-ATTC-A			Uncertain significance (Jun 29, 2023)
16-28842995-T-C		Combined oxidative phosphorylation defect type 4 • Inborn genetic diseases	Uncertain significance (Oct 24, 2022)
16-28843006-G-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
16-28843010-T-C			Uncertain significance (Sep 02, 2022)
16-28843035-G-A			Likely benign (Jun 01, 2021)
16-28843051-T-C		Combined oxidative phosphorylation defect type 4 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 22, 2024)
16-28843059-T-G			Likely benign (Jan 15, 2024)
16-28843072-C-T			Uncertain significance (Dec 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TUFM	protein_coding	protein_coding	ENST00000313511	10	3998

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00418	0.989	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.40	205	269	0.761	0.0000174	2918
Missense in Polyphen		62	108.29	0.57255		1122
Synonymous	0.0910	114	115	0.989	0.00000743	982
Loss of Function	2.37	7	17.8	0.393	0.00000101	220

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.0000546	0.0000544
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000880	0.0000791
Middle Eastern	0.0000546	0.0000544
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. Plays also a role in the regulation of autophagy and innate immunity. Recruits ATG5-ATG12 and NLRX1 at mitochondria and serves as a checkpoint of the RIG-I/DDX58-MAVS pathway. In turn, inhibits RLR-mediated type I interferon while promoting autophagy. {ECO:0000269|PubMed:22749352, ECO:0000269|PubMed:28407488}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 4 (COXPD4) [MIM:610678]: A mitochondrial disease resulting in neonatal lactic acidosis, rapidly progressive encephalopathy, severely decreased mitochondrial protein synthesis, and combined deficiency of mtDNA- related mitochondrial respiratory chain complexes. {ECO:0000269|PubMed:17160893}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Translation;Metabolism of proteins;Purine metabolism;Mitochondrial translation elongation;Mitochondrial translation (Consensus)

Recessive Scores

• pRec: 0.151

Intolerance Scores

• loftool: 0.511
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.316
• hipred: Y
• hipred_score: 0.743
• ghis: 0.572

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.923

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tufm

Gene ontology

• Biological process: translational elongation;response to ethanol;mitochondrial translational elongation
• Cellular component: mitochondrion;membrane;mitochondrial nucleoid;myelin sheath;synapse;extracellular exosome
• Molecular function: RNA binding;translation elongation factor activity;GTPase activity;protein binding;GTP binding