TIMMDC1

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

Basic information

Region (hg38): 3:119498547-119525090

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 I deficiency, nuclear type 31 (Moderate), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex I 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 (62 variants)
• not_specified (47 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_31 (13 variants)
• TIMMDC1-related_disorder (5 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_1 (5 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. These statistics are base on transcript: NM_000016589.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	11	1	13
missense		2	64	3	1	70
nonsense		2	3			5
start loss		1				1
frameshift		1	3			4
splice donor/acceptor (+/-2bp)		3				3
Total	0	9	71	14	2

Highest pathogenic variant AF is 0.00010511102

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