TOMM6

Summary

TOMM6 (translocase of outer mitochondrial membrane 6, HGNC:34528) is a protein-coding gene on chromosome 6p21.1, encoding Mitochondrial import receptor subunit TOM6 homolog (Q96B49). Component of the translocase of the outer membrane of mitochondria (TOM) complex essential for the recognition and translocation of cytosolically synthesized mitochondrial preproteins.

Predicted to be involved in protein insertion into mitochondrial outer membrane. Located in mitochondrion.

Source: NCBI Gene 100188893 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_001382294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34528
Approved symbol	TOMM6
Name	translocase of outer mitochondrial membrane 6
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	OBTP, Tom6
Ensembl gene	ENSG00000214736
Ensembl biotype	protein_coding
OMIM	616168
Entrez	100188893

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000398881, ENST00000398884, ENST00000931251, ENST00000931252, ENST00000931253, ENST00000931254, ENST00000931255

RefSeq mRNA: 2 — MANE Select: NM_001382294 NM_001134493, NM_001382294

CCDS: CCDS47424

Canonical transcript exons

ENST00000398881 — 3 exons

Exon	Start	End
ENSE00001838603	41787694	41787825
ENSE00001872972	41789568	41789895
ENSE00003612841	41789232	41789336

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 200.4256 / max 1916.1599, expressed in 1827 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67775	189.7939	1824
67774	6.7815	1772
67773	3.8502	1559

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	99.05	gold quality
islet of Langerhans	UBERON:0000006	99.03	gold quality
right adrenal gland cortex	UBERON:0035827	98.99	gold quality
left adrenal gland	UBERON:0001234	98.98	gold quality
left adrenal gland cortex	UBERON:0035825	98.98	gold quality
adrenal gland	UBERON:0002369	98.88	gold quality
granulocyte	CL:0000094	98.87	gold quality
body of pancreas	UBERON:0001150	98.86	gold quality
lymph node	UBERON:0000029	98.85	gold quality
leukocyte	CL:0000738	98.84	gold quality
monocyte	CL:0000576	98.83	gold quality
metanephros cortex	UBERON:0010533	98.81	gold quality
pancreas	UBERON:0001264	98.79	gold quality
lower esophagus mucosa	UBERON:0035834	98.77	gold quality
prostate gland	UBERON:0002367	98.74	gold quality
rectum	UBERON:0001052	98.72	gold quality
esophagus mucosa	UBERON:0002469	98.72	gold quality
skin of abdomen	UBERON:0001416	98.71	gold quality
cortex of kidney	UBERON:0001225	98.70	gold quality
spleen	UBERON:0002106	98.70	gold quality
fallopian tube	UBERON:0003889	98.68	gold quality
zone of skin	UBERON:0000014	98.65	gold quality
left lobe of thyroid gland	UBERON:0001120	98.65	gold quality
left ovary	UBERON:0002119	98.65	gold quality
right lobe of thyroid gland	UBERON:0001119	98.64	gold quality
heart left ventricle	UBERON:0002084	98.64	gold quality
adult mammalian kidney	UBERON:0000082	98.63	gold quality
thyroid gland	UBERON:0002046	98.63	gold quality
skin of leg	UBERON:0001511	98.62	gold quality
nucleus accumbens	UBERON:0001882	98.62	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	36.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting TOMM6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-129-5P	99.88	70.26	3273
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-581	98.39	67.42	835
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-346	97.01	66.97	662
HSA-MIR-6866-5P	96.64	68.06	624
HSA-MIR-632	96.08	67.17	798
HSA-MIR-208A-3P	95.87	66.51	397
HSA-MIR-208B-3P	95.87	66.56	396

Literature-anchored findings (GeneRIF, showing 1)

• The human counterparts of Tom5 and Tom6, together with the other components including Tom7, were identified in the preprotein translocase complex. (PMID:18331822)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	tomm6	ENSDARG00000097797
mus_musculus	Tomm6	ENSMUSG00000033475

Protein

Protein identifiers

Mitochondrial import receptor subunit TOM6 homolog — Q96B49 (reviewed: Q96B49)

Alternative names: Overexpressed breast tumor protein, Translocase of outer membrane 6 kDa subunit homolog

All UniProt accessions (1): Q96B49

UniProt curated annotations — full annotation on UniProt →

Function. Component of the translocase of the outer membrane of mitochondria (TOM) complex essential for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. The TOM complex associates with the ion channel VDAC2 and PINK1 kinase at depolarized mitochondria, this interaction stabilizes PINK1 at the outer mitochondrial membrane and triggers downstream mitophagy by the recruitment of the E3 ubiquitin ligase PRKN.

Subunit / interactions. Part of the translocase of the outer mitochondrial membrane (TOM complex) consisting of at least TOMM5, TOMM6, TOMM7, TOMM20, TOMM22 and TOMM40. TOMM70 may also be found in the TOM complex. The TOM complex interacts with the VDAC2 homodimer. Upon mitochondrial depolarization, the TOM-VDAC assembly interacts with PINK1; the interaction stabilizes PINK1 at the outer mitochondrial membrane and triggers downstream mitophagy.

Subcellular location. Mitochondrion outer membrane.

Similarity. Belongs to the Tom6 family.

RefSeq proteins (2): NP_001127965, NP_001369223* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029182	TOMM6	Family

Pfam: PF15184

UniProt features (12 total): helix 2, topological domain 2, initiator methionine 1, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
7VD2	ELECTRON MICROSCOPY	2.53
7VBY	ELECTRON MICROSCOPY	2.54
9EII	ELECTRON MICROSCOPY	2.75
9JXV	ELECTRON MICROSCOPY	2.89
8XDN	ELECTRON MICROSCOPY	2.93
7CP9	ELECTRON MICROSCOPY	3
9EIH	ELECTRON MICROSCOPY	3.1
9EIJ	ELECTRON MICROSCOPY	3.3
7CK6	ELECTRON MICROSCOPY	3.4
7VC4	ELECTRON MICROSCOPY	3.74
7VDD	ELECTRON MICROSCOPY	3.74
8XVA	ELECTRON MICROSCOPY	5.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96B49-F1	71.39	0.13

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-5205685	PINK1-PRKN Mediated Mitophagy

MSigDB gene sets: 97 (showing top): GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE, GOCC_OUTER_MITOCHONDRIAL_MEMBRANE_PROTEIN_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_MITOCHONDRIAL_PROTEIN_CONTAINING_COMPLEX, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, GOCC_ORGANELLE_ENVELOPE

GO Biological Process (2): protein transport (GO:0015031), protein insertion into mitochondrial outer membrane (GO:0045040)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), TOM complex (GO:0140596), mitochondrial outer membrane translocase complex (GO:0005742), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein localization	1
Mitophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
intracellular protein localization	1
establishment of protein localization	1
outer mitochondrial membrane organization	1
protein insertion into mitochondrial membrane	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
mitochondrial outer membrane translocase complex	1
outer mitochondrial membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOMM6	TOMM7	Q9P0U1	998
TOMM6	TOMM5	Q8N4H5	998
TOMM6	TOMM22	Q9NS69	996
TOMM6	TOMM40	O96008	996
TOMM6	TOMM20	Q15388	988
TOMM6	TOMM70	O94826	984
TOMM6	SAMM50	Q9Y512	595
TOMM6	TIMM17A	Q99595	593
TOMM6	TIMM50	Q3ZCQ8	582
TOMM6	TIMM21	Q9BVV7	581
TOMM6	DNAJC19	Q96DA6	543
TOMM6	TIMM44	O43615	541
TOMM6	TIMM10	P62072	507
TOMM6	TIMM9	Q9Y5J7	507
TOMM6	TOMM34	Q15785	462

IntAct

47 interactions, top by confidence:

A	B	Type	Score
CD68	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
SEC61A2	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
TOMM6	C1orf159	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
TOMM6	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
TOMM6	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
TOMM6	CERS4	psi-mi:“MI:0915”(physical association)	0.560
AQP6	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
SLC18A2	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
ODF4	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	TOMM6	psi-mi:“MI:0915”(physical association)	0.560
WLS	TOMM6	psi-mi:“MI:0915”(physical association)	0.490
SLC11A2	TOMM6	psi-mi:“MI:0915”(physical association)	0.370
WLS	TOMM6	psi-mi:“MI:0915”(physical association)	0.370
	AP3D1	psi-mi:“MI:0914”(association)	0.350
TOMM6	TOMM40	psi-mi:“MI:0914”(association)	0.350
CD68	TOMM6	psi-mi:“MI:0915”(physical association)	0.000
SEC61A2	TOMM6	psi-mi:“MI:0915”(physical association)	0.000
TOMM6		psi-mi:“MI:0915”(physical association)	0.000
TOMM6	SLC10A1	psi-mi:“MI:0915”(physical association)	0.000
TOMM6	TMEM14B	psi-mi:“MI:0915”(physical association)	0.000
TOMM6	CD68	psi-mi:“MI:0915”(physical association)	0.000
TOMM6	ERGIC3	psi-mi:“MI:0915”(physical association)	0.000
TOMM6	CERS4	psi-mi:“MI:0915”(physical association)	0.000
TOMM6	AQP6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): TOMM6 (PCA), IMPAD1 (Co-fractionation), TOMM6 (Co-fractionation), TOMM6 (Co-fractionation), VAPA (Co-fractionation), TOMM6 (Co-fractionation), TOMM6 (Co-fractionation), TOMM6 (Co-fractionation), TOMM6 (Co-fractionation), TOMM6 (Co-fractionation), TOMM6 (Co-fractionation), TOMM6 (Co-fractionation), TOMM6 (Co-fractionation), CYB5R1 (Co-fractionation), TOMM6 (Co-fractionation)

ESM2 similar proteins: A0A1B0GQX3, A0A1B0GRQ0, A0A1B0GVT2, A0A590UK83, A4QNL6, A5D7B5, A6H770, B3DHH5, E1BAR0, O75324, P0DKX4, P35803, P56695, P58511, P61807, P61808, P84889, Q12016, Q15053, Q17Q87, Q28793, Q2TZ20, Q3MHM8, Q4V786, Q4V921, Q4VBG5, Q56JY4, Q5RBD8, Q5U2S1, Q68FV2, Q6DGP4, Q6GLN5, Q758B5, Q80Z96, Q80ZU4, Q876Z1, Q8BH07, Q8BT42, Q8GUM4, Q8R0W6

Diamond homologs: Q56JY4, Q96B49, Q9CQN3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TOMM6	“form complex”	“TOM40 complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

17 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

302 predictions. Top by Δscore:

Variant	Effect	Δscore
6:41787823:G:GT	donor_gain	1.0000
6:41787824:AG:A	donor_loss	1.0000
6:41787825:GG:G	donor_loss	1.0000
6:41789530:GTTCT:G	acceptor_gain	1.0000
6:41787811:G:GT	donor_gain	0.9900
6:41787812:A:T	donor_gain	0.9900
6:41787822:GGAG:G	donor_gain	0.9900
6:41787841:G:GT	donor_gain	0.9900
6:41789529:A:AG	acceptor_gain	0.9900
6:41789530:G:GG	acceptor_gain	0.9900
6:41789530:GTT:G	acceptor_gain	0.9900
6:41789559:T:TA	acceptor_gain	0.9900
6:41787823:GAG:G	donor_gain	0.9800
6:41789333:GTAG:G	donor_gain	0.9800
6:41789567:GACAA:G	acceptor_gain	0.9800
6:41787842:A:T	donor_gain	0.9700
6:41789530:GTTC:G	acceptor_gain	0.9700
6:41789556:ATCT:A	acceptor_gain	0.9700
6:41789566:A:AG	acceptor_gain	0.9700
6:41789567:G:GG	acceptor_gain	0.9700
6:41789567:GACA:G	acceptor_gain	0.9700
6:41789562:TTGCA:T	acceptor_loss	0.9600
6:41789563:TGCA:T	acceptor_loss	0.9600
6:41789564:GCAGA:G	acceptor_loss	0.9600
6:41789565:C:CG	acceptor_loss	0.9600
6:41789567:G:GA	acceptor_loss	0.9600
6:41789567:GAC:G	acceptor_gain	0.9600
6:41787807:A:G	donor_gain	0.9500
6:41789559:T:A	acceptor_loss	0.9500
6:41787826:G:GG	donor_gain	0.9400

AlphaMissense

480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:41789267:G:A	G55E	0.995
6:41789257:T:C	F52L	0.992
6:41789259:T:A	F52L	0.992
6:41789259:T:G	F52L	0.992
6:41789261:C:A	A53D	0.992
6:41789282:G:T	R60M	0.992
6:41787818:T:C	F41L	0.991
6:41787820:C:A	F41L	0.991
6:41787820:C:G	F41L	0.991
6:41789252:G:A	G50E	0.991
6:41789266:G:A	G55R	0.991
6:41789266:G:C	G55R	0.991
6:41789251:G:A	G50R	0.990
6:41789251:G:C	G50R	0.990
6:41787819:T:G	F41C	0.987
6:41787819:T:C	F41S	0.986
6:41787825:G:T	R43M	0.985
6:41789247:T:A	N48K	0.985
6:41789247:T:G	N48K	0.985
6:41789255:T:A	L51H	0.985
6:41789272:T:A	W57R	0.985
6:41789272:T:C	W57R	0.985
6:41789307:G:A	M68I	0.985
6:41789307:G:C	M68I	0.985
6:41789307:G:T	M68I	0.985
6:41789258:T:C	F52S	0.983
6:41789293:G:C	D64H	0.983
6:41789294:A:T	D64V	0.983
6:41789279:C:A	A59D	0.982
6:41789258:T:G	F52C	0.980

dbSNP variants (sampled 300 via entrez): RS1000565706 (6:41787689 C>T), RS1002066436 (6:41786702 T>C), RS1002401169 (6:41787387 A>C), RS1003020767 (6:41790184 C>T), RS1003081403 (6:41789722 C>T), RS1004295000 (6:41788134 C>T), RS1006088554 (6:41786312 T>C), RS1007206913 (6:41786593 C>T), RS1007636088 (6:41785882 A>G), RS1007879765 (6:41788163 G>T), RS1008837193 (6:41789133 C>A,G,T), RS1008868895 (6:41787556 G>A,C), RS1008921044 (6:41787480 G>A,T), RS1009699296 (6:41787084 A>G), RS1009924098 (6:41786463 G>A)

Disease associations

OMIM: gene MIM:616168 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012227_976	Hip circumference adjusted for BMI	5.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases abundance, affects expression, affects cotreatment	2
ginger extract	affects expression, increases abundance, affects cotreatment	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
ochratoxin A	decreases expression, affects cotreatment	1
ferrous chloride	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
chloropicrin	decreases expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Citrinin	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3JT	Abcam HEK293T TOMM6 KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.