TIMMDC1

translocase of inner mitochondrial membrane domain containing 1, the group of Mitochondrial complex I assembly complex|Tim17 family

Basic information

Region (hg38): 3:119498546-119525090

Previous symbols: [ "C3orf1" ]

Links

ENSG00000113845 ∙ NCBI:51300 ∙ OMIM:615534 ∙ HGNC:1321 ∙ Uniprot:Q9NPL8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex 1 deficiency, nuclear type 31 (Moderate), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 31 (Strong), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 31	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	Audiologic/Otolaryngologic; Biochemical; Neurologic	28604674

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TIMMDC1 gene.

• not provided (58 variants)
• Inborn genetic diseases (15 variants)
• Mitochondrial complex 1 deficiency, nuclear type 31 (13 variants)
• Mitochondrial complex I deficiency, nuclear type 1 (5 variants)
• not specified (3 variants)
• Leigh syndrome (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 TIMMDC1 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	5	2	8
missense			37	1	3	41
nonsense	1		3			4
start loss		1				1
frameshift		1	2			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)		2				2
splice region			1	4		5
non coding	1		1	5	7	14
Total	2	4	46	11	12

Highest pathogenic variant AF is 0.000105

Variants in TIMMDC1

This is a list of pathogenic ClinVar variants found in the TIMMDC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-119498732-C-T		Mitochondrial complex 1 deficiency, nuclear type 31	Uncertain significance (Jun 24, 2019)
3-119498734-A-G		Mitochondrial complex 1 deficiency, nuclear type 31	Likely pathogenic (Oct 11, 2022)
3-119498744-C-A			Uncertain significance (Jul 12, 2022)
3-119498762-G-T			Uncertain significance (Feb 08, 2022)
3-119498791-C-T		not specified	Uncertain significance (Aug 08, 2023)
3-119498805-T-C			Likely benign (Dec 07, 2023)
3-119498808-C-G		TIMMDC1-related disorder	Likely benign (Jul 18, 2019)
3-119498824-G-A		not specified	Uncertain significance (Dec 01, 2022)
3-119498838-TGAG-T			Uncertain significance (Nov 27, 2023)
3-119498857-C-T		not specified	Uncertain significance (Dec 22, 2023)
3-119498868-C-T		TIMMDC1-related disorder	Likely benign (Dec 07, 2023)
3-119498879-A-G			Uncertain significance (Apr 15, 2022)
3-119498902-C-A		not specified	Uncertain significance (Jan 06, 2023)
3-119498908-C-T		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Apr 17, 2018)
3-119498909-G-A			Uncertain significance (Nov 29, 2022)
3-119498922-CAA-C		Mitochondrial complex I deficiency, nuclear type 1	Likely pathogenic (Mar 01, 2023)
3-119498929-T-C		Mitochondrial complex 1 deficiency, nuclear type 31	Likely pathogenic (Mar 28, 2023)
3-119498938-C-T			Likely benign (May 10, 2022)
3-119498942-G-T			Benign (Jan 29, 2024)
3-119500718-A-G			Uncertain significance (May 15, 2022)
3-119500723-G-C		not specified	Uncertain significance (Feb 15, 2023)
3-119500726-A-G		TIMMDC1-related disorder	Benign (Jan 31, 2024)
3-119500730-T-C		not specified	Uncertain significance (Jul 28, 2022)
3-119500732-T-C		TIMMDC1-related disorder	Benign (Jan 25, 2024)
3-119500748-C-T			Uncertain significance (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIMMDC1	protein_coding	protein_coding	ENST00000494664	7	26559

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.11e-8	0.334	125702	0	45	125747	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00439	156	156	0.999	0.00000800	1827
Missense in Polyphen		40	49.659	0.80549		560
Synonymous	-1.01	67	57.3	1.17	0.00000278	573
Loss of Function	0.726	14	17.3	0.811	9.79e-7	177

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000279	0.000275
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000231	0.000229
Middle Eastern	0.00	0.00
South Asian	0.000397	0.000392
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Participates in constructing the membrane arm of complex I. {ECO:0000269|PubMed:24191001}.
• Pathway: Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.0658

Intolerance Scores

• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.37

Haploinsufficiency Scores

• pHI: 0.0207
• hipred: N
• hipred_score: 0.144
• ghis: 0.450

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Timmdc1
• Phenotype: hematopoietic system phenotype; 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); immune system phenotype

Gene ontology

• Biological process: mitochondrial respiratory chain complex I assembly
• Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: protein binding