TTC19

tetratricopeptide repeat domain 19, the group of Mitochondrial respiratory chain complex assembly factors|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 17:15999784-16045015

Links

ENSG00000011295

∙ NCBI:54902 ∙ OMIM:613814 ∙ HGNC:26006 ∙ Uniprot:Q6DKK2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

mitochondrial complex III deficiency nuclear type 2 (Strong), mode of inheritance: AR
mitochondrial complex III deficiency nuclear type 2 (Strong), mode of inheritance: AR
mitochondrial complex III deficiency (Supportive), mode of inheritance: AR
mitochondrial complex III deficiency nuclear type 2 (Moderate), mode of inheritance: AR
Leigh syndrome (Definitive), mode of inheritance: AR
mitochondrial complex III deficiency nuclear type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex III deficiency, nuclear type 2	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; Musculoskeletal; Neurologic	21278747; 23532514; 24368687; 24397319
Individuals may suffer acute episodes of metabolic crisis; Treatment with Mitochondrial cocktail type therapy may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTC19 gene.

not_provided (166 variants)
Inborn_genetic_diseases (70 variants)
Mitochondrial_complex_III_deficiency_nuclear_type_2 (52 variants)
not_specified (18 variants)
TTC19-related_disorder (7 variants)
Mitochondrial_disease (2 variants)
Autism (1 variants)
Mitochondrial_complex_III_deficiency_nuclear_type_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTC19 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017775.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	40 clinvar	1 clinvar	44
missense		2 clinvar	93 clinvar	15 clinvar		110
nonsense	9 clinvar	2 clinvar	2 clinvar			13
start loss		1				1
frameshift	3 clinvar	2 clinvar	1 clinvar		1 clinvar	7
splice donor/acceptor (+/-2bp)	1 clinvar	8 clinvar	1 clinvar			10
Total	13	15	100	55	2

Highest pathogenic variant AF is 0.0000818457

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTC19	protein_coding	protein_coding	ENST00000261647	10	45636

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.38e-8	0.594	125621	0	127	125748	0.000505

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0827	176	179	0.983	0.00000880	2434
Missense in Polyphen		51	56.365	0.90482		761
Synonymous	-1.21	79	66.4	1.19	0.00000331	745
Loss of Function	1.16	15	20.7	0.725	9.77e-7	251

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000735	0.000735
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000381	0.000381
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000766	0.000765
Middle Eastern	0.000381	0.000381
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Required for the preservation of the structural and functional integrity of mitochondrial respiratory complex III by allowing the physiological turnover of the Rieske protein UQCRFS1 (PubMed:21278747, PubMed:28673544). Involved in the clearance of UQCRFS1 N-terminal fragments, which are produced upon incorporation of UQCRFS1 into the complex III and whose presence is detrimental for its catalytic activity (PubMed:28673544). {ECO:0000269|PubMed:21278747, ECO:0000269|PubMed:28673544}.;
Disease: DISEASE: Mitochondrial complex III deficiency, nuclear 2 (MC3DN2) [MIM:615157]: A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance. {ECO:0000269|PubMed:21278747}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0786

Haploinsufficiency Scores

pHI: 0.255
hipred: N
hipred_score: 0.144
ghis: 0.413

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.0761

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ttc19
Phenotype

Gene ontology

Biological process: mitotic cytokinesis;mitochondrial respiratory chain complex III assembly;oxidation-reduction process
Cellular component: mitochondrion;mitochondrial inner membrane;centrosome;midbody;respirasome
Molecular function: protein binding