TIMM22

translocase of inner mitochondrial membrane 22, the group of Tim17 family|TIM22 complex

Basic information

Region (hg38): 17:997129-1003671

Previous symbols: [ "TEX4" ]

Links

ENSG00000177370

∙ NCBI:29928 ∙ OMIM:607251 ∙ HGNC:17317 ∙ Uniprot:Q9Y584 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

combined oxidative phosphorylation deficiency 43 (Limited), mode of inheritance: AR
combined oxidative phosphorylation deficiency 43 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 43	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; Neurologic	30452684

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TIMM22 gene.

not_specified (25 variants)
not_provided (4 variants)
TIMM22-related_disorder (2 variants)
Combined_oxidative_phosphorylation_deficiency_43 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIMM22 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000013337.4. 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				2 clinvar		2
missense			24 clinvar	3 clinvar		27
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	24	5	0

Highest pathogenic variant AF is 0.000024645415

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIMM22	protein_coding	protein_coding	ENST00000327158	4	6555

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000397	0.401	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.220	125	118	1.06	0.00000614	1241
Missense in Polyphen		31	40.456	0.76627		400
Synonymous	-0.466	50	46.0	1.09	0.00000246	402
Loss of Function	0.252	7	7.76	0.902	3.26e-7	99

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000273	0.000272
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000890	0.0000879
Middle Eastern	0.000163	0.000163
South Asian	0.000393	0.000392
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps (By similarity). {ECO:0000250|UniProtKB:Q12328}.;
Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Recessive Scores

pRec: 0.107

Intolerance Scores

loftool: 0.694
rvis_EVS: 0.1
rvis_percentile_EVS: 61.49

Haploinsufficiency Scores

pHI: 0.155
hipred: Y
hipred_score: 0.558
ghis: 0.512

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.687

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Timm22
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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: protein targeting to mitochondrion;protein insertion into mitochondrial inner membrane
Cellular component: mitochondrial inner membrane;integral component of membrane;TIM22 mitochondrial import inner membrane insertion complex
Molecular function: protein binding;protein transmembrane transporter activity;mitochondrion targeting sequence binding