TOMM40

protein-coding

translocase of outer mitochondrial membrane 40, the group of Translocase of outer mitochondrial membrane complex

Gene summary

The protein encoded by this gene is localized in the outer membrane of the mitochondria. It is the channel-forming subunit of the translocase of the mitochondrial outer membrane (TOM) complex that is essential for import of protein precursors into mitochondria. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

MANE transcript

NM_001128917.2

Inheritance

—

ClinVar variants

U:47B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:44,890,569-44,903,689

External References & Databases

Ensembl (ENSG00000130204)

Transcript & Mutation Effects

hg38 • Region Span ~13.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TOMM40 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001128917.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			46 clinvar	2 clinvar	1 clinvar	49
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	47	3	2	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001128917.2	RefSeq	NP_001122389.1	9	MANE Select
ENST00000426677.7	Ensembl	ENSP00000410339.1	9	MANE Select
NM_001128916.2	RefSeq	NP_001122388.1	9	Standard
NM_006114.3	RefSeq	NP_006105.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
Metabolism of proteins
Pink/Parkin Mediated Mitophagy
Mitophagy
Mitochondrial protein import

Biological Process

protein targeting to mitochondrion
ion transport
protein import into mitochondrial matrix

Molecular Function

protein binding
protein transmembrane transporter activity
porin activity

Cellular Component

mitochondrion
mitochondrial outer membrane
mitochondrial outer membrane translocase complex
mitochondrial inner membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000426677
Coding exons: 9
Length: 13121
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125692
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.16	100	182	0.549	0.0000102	2294
Missense (PolyPhen)		13	44.099	0.29479		608
Synonymous	1.01	67	78.4	0.855	0.00000478	760
Loss of Function	3.53	0	14.5	0.00	6.19e-7	179

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Channel-forming protein essential for import of protein precursors into mitochondria. {ECO:0000269|PubMed:15644312}.;

Recessive Scores

pRec: 0.132

Intolerance Scores

RVIS EVS: -0.34
RVIS percentile EVS: 30.37

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.994

Gene Damage Prediction

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