TOMM5

Summary

TOMM5 (translocase of outer mitochondrial membrane 5, HGNC:31369) is a protein-coding gene on chromosome 9p13.2, encoding Mitochondrial import receptor subunit TOM5 homolog (Q8N4H5). 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. Part of mitochondrial outer membrane translocase complex.

Source: NCBI Gene 401505 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001001790

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31369
Approved symbol	TOMM5
Name	translocase of outer mitochondrial membrane 5
Location	9p13.2
Locus type	gene with protein product
Status	Approved
Aliases	bA613M10.3, Tom5
Ensembl gene	ENSG00000175768
Ensembl biotype	protein_coding
OMIM	616169
Entrez	401505

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000321301, ENST00000377773, ENST00000401811, ENST00000540941, ENST00000544379, ENST00000918072

RefSeq mRNA: 3 — MANE Select: NM_001001790 NM_001001790, NM_001134484, NM_001134485

CCDS: CCDS43803, CCDS47967, CCDS47968

Canonical transcript exons

ENST00000321301 — 2 exons

Exon	Start	End
ENSE00001242363	37592412	37592597
ENSE00003527794	37588413	37588932

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.7649 / max 553.9949, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100739	82.9135	1824
100738	4.8514	1589

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.51	gold quality
adrenal tissue	UBERON:0018303	97.98	gold quality
body of pancreas	UBERON:0001150	97.62	gold quality
mucosa of transverse colon	UBERON:0004991	97.60	gold quality
islet of Langerhans	UBERON:0000006	97.57	gold quality
adult mammalian kidney	UBERON:0000082	97.32	gold quality
left coronary artery	UBERON:0001626	97.14	gold quality
right adrenal gland	UBERON:0001233	97.13	gold quality
left adrenal gland	UBERON:0001234	97.09	gold quality
hypothalamus	UBERON:0001898	97.09	gold quality
left adrenal gland cortex	UBERON:0035825	97.08	gold quality
pancreas	UBERON:0001264	97.07	gold quality
omental fat pad	UBERON:0010414	97.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.07	gold quality
muscle of leg	UBERON:0001383	97.04	gold quality
gastrocnemius	UBERON:0001388	96.99	gold quality
lymph node	UBERON:0000029	96.97	gold quality
right coronary artery	UBERON:0001625	96.90	gold quality
substantia nigra	UBERON:0002038	96.90	gold quality
right adrenal gland cortex	UBERON:0035827	96.90	gold quality
ganglionic eminence	UBERON:0004023	96.87	gold quality
esophagus mucosa	UBERON:0002469	96.84	gold quality
putamen	UBERON:0001874	96.80	gold quality
caudate nucleus	UBERON:0001873	96.74	gold quality
adrenal gland	UBERON:0002369	96.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.74	gold quality
nucleus accumbens	UBERON:0001882	96.72	gold quality
endometrium	UBERON:0001295	96.70	gold quality
thoracic aorta	UBERON:0001515	96.69	gold quality
duodenum	UBERON:0002114	96.69	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	22.45
E-MTAB-9067	yes	20.17
E-ANND-3	yes	14.13
E-MTAB-6819	no	1454.57
E-MTAB-9689	no	827.15
E-MTAB-7407	no	571.60
E-CURD-112	no	3.66
E-HCAD-31	no	2.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting TOMM5, 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-3692-3P	99.98	70.27	2139
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-517A-3P	98.02	72.72	114
HSA-MIR-517B-3P	98.02	72.72	114
HSA-MIR-517C-3P	98.02	72.62	114
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-4536-3P	97.06	66.88	175
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-4513	95.04	67.06	727
HSA-MIR-6855-3P	95.04	66.57	725

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

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	tomm5	ENSDARG00000068265

Protein

Protein identifiers

Mitochondrial import receptor subunit TOM5 homolog — Q8N4H5 (reviewed: Q8N4H5)

All UniProt accessions (3): Q8N4H5, F8W8Z9, H0YFG9

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 Tom5 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N4H5-1	1	yes
Q8N4H5-2	2
Q8N4H5-3	3

RefSeq proteins (3): NP_001001790, NP_001127956, NP_001127957 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019603	Tom5	Family
IPR029179	TOMM5_metazoa	Family

Pfam: PF10642

UniProt features (9 total): topological domain 2, splice variant 2, chain 1, transmembrane region 1, modified residue 1, cross-link 1, helix 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-Q8N4H5-F1	88.18	0.74

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 (2): 1, 10

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: 103 (showing top): PAL_PRMT5_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, WEI_MYCN_TARGETS_WITH_E_BOX, chr9p13, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, RYTTCCTG_ETS2_B, BASAKI_YBX1_TARGETS_UP, GOBP_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION

GO Biological Process (3): obsolete protein targeting to mitochondrion (GO:0006626), protein transport (GO:0015031), protein insertion into mitochondrial outer membrane (GO:0045040)

GO Molecular Function (0):

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), mitochondrial outer membrane translocase complex (GO:0005742), TOM complex (GO:0140596), 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
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
outer mitochondrial membrane protein complex	1
mitochondrial outer membrane translocase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOMM5	TOMM6	Q96B49	998
TOMM5	TOMM7	Q9P0U1	997
TOMM5	TOMM22	Q9NS69	996
TOMM5	TOMM40	O96008	996
TOMM5	TOMM70	O94826	992
TOMM5	TOMM20	Q15388	992
TOMM5	EMC1	Q8N766	629
TOMM5	TIMM13	P62206	616
TOMM5	TIMM17A	Q99595	598
TOMM5	TIMM50	Q3ZCQ8	595
TOMM5	TIMM21	Q9BVV7	582
TOMM5	TOMM40L	Q969M1	576
TOMM5	TIMM44	O43615	571
TOMM5	SAMM50	Q9Y512	541
TOMM5	DNAJC19	Q96DA6	540

IntAct

33 interactions, top by confidence:

A	B	Type	Score
TOMM22	TOMM40	psi-mi:“MI:0914”(association)	0.740
TOMM5	PPIB	psi-mi:“MI:0915”(physical association)	0.400
USB1	TOMM5	psi-mi:“MI:0914”(association)	0.350
SHLD3		psi-mi:“MI:0914”(association)	0.350
CISD3	POLRMT	psi-mi:“MI:0914”(association)	0.350
OCIAD1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
OPA3	NDUFS8	psi-mi:“MI:0914”(association)	0.350
ADCK1	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
CISD3	TIMM44	psi-mi:“MI:0914”(association)	0.350
OCIAD1	NDUFS5	psi-mi:“MI:0914”(association)	0.350
COPZ1	ATL3	psi-mi:“MI:0914”(association)	0.350
FKBP8	GNB5	psi-mi:“MI:0914”(association)	0.350
RAB1A	SCAMP3	psi-mi:“MI:0914”(association)	0.350
RAB2A	TOMM40	psi-mi:“MI:0914”(association)	0.350
TOMM20	TIMM44	psi-mi:“MI:0914”(association)	0.350
TOMM6	TOMM40	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
ATF1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ATF5	PTGES	psi-mi:“MI:0914”(association)	0.350
PPARA	PTGES	psi-mi:“MI:0914”(association)	0.350
SOX2	MYO1C	psi-mi:“MI:0914”(association)	0.350
CREB1	NOP56	psi-mi:“MI:0914”(association)	0.350
ATF1	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
CREB1	ACOT7	psi-mi:“MI:0914”(association)	0.350
ERBB2	AP3B1	psi-mi:“MI:0914”(association)	0.350
PPARA	GOLIM4	psi-mi:“MI:0914”(association)	0.350
ATF2	ABLIM1	psi-mi:“MI:0914”(association)	0.350
ATF3	C11orf98	psi-mi:“MI:0914”(association)	0.350
ERBB2	AGPS	psi-mi:“MI:0914”(association)	0.350

BioGRID (139): TOMM5 (Affinity Capture-MS), TOMM5 (Affinity Capture-MS), TOMM5 (Affinity Capture-MS), TOMM5 (Affinity Capture-MS), BAG6 (Reconstituted Complex), UBQLN1 (Reconstituted Complex), UBQLN2 (Reconstituted Complex), ASNA1 (Reconstituted Complex), TOMM5 (Co-fractionation), VDAC3 (Co-fractionation), TOMM5 (Co-fractionation), TOMM5 (Co-fractionation), SDF2 (Co-fractionation), TOMM5 (Co-fractionation), C14orf1 (Co-fractionation)

ESM2 similar proteins: A0A1B0GUW7, A2BRN6, A3PDG2, A4ZUC6, A7MNL7, A8G5C7, A8YXZ8, B1AXP6, B1WYX8, B2J6T0, B5XQ45, B7JYE8, B7KH62, B8HVD7, C0H3U2, F5HHL7, O12163, O70891, P05139, P0C0Y1, P0DPP7, P27387, P27388, P30248, P30395, P32273, P35109, P39222, P58569, P80100, P80101, Q03561, Q05807, Q10ZK6, Q25BI5, Q31AG7, Q3J1A3, Q3MC09, Q4G3E7, Q54697

Diamond homologs: A8YXZ8, B1AXP6, Q5R676, Q8N4H5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TOMM5	“form complex”	“TOM40 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial protein import	5	24.0×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of gene expression	5	9.7×	5e-03
intracellular protein transport	6	9.0×	2e-03
negative regulation of apoptotic process	7	5.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

881 predictions. Top by Δscore:

Variant	Effect	Δscore
9:37588810:CA:C	donor_gain	1.0000
9:37588928:TGGAG:T	acceptor_gain	1.0000
9:37588929:GGAG:G	acceptor_gain	1.0000
9:37588930:GAG:G	acceptor_gain	1.0000
9:37588930:GAGC:G	acceptor_loss	1.0000
9:37588931:AG:A	acceptor_gain	1.0000
9:37588933:C:CC	acceptor_gain	1.0000
9:37588933:C:T	acceptor_loss	1.0000
9:37592410:A:AC	donor_gain	1.0000
9:37592411:C:CA	donor_gain	1.0000
9:37592411:C:CC	donor_gain	1.0000
9:37592411:CTGA:C	donor_gain	1.0000
9:37592414:A:AC	donor_gain	1.0000
9:37592415:C:CC	donor_gain	1.0000
9:37592465:T:TA	donor_gain	1.0000
9:37592478:T:TA	donor_gain	1.0000
9:37588773:A:C	donor_gain	0.9900
9:37588809:A:AC	donor_gain	0.9900
9:37588810:C:CC	donor_gain	0.9900
9:37588930:GAGCT:G	acceptor_gain	0.9900
9:37588931:AGC:A	acceptor_gain	0.9900
9:37588931:AGCTG:A	acceptor_gain	0.9900
9:37588932:GC:G	acceptor_gain	0.9900
9:37588932:GCT:G	acceptor_gain	0.9900
9:37588933:C:A	acceptor_gain	0.9900
9:37588933:C:G	acceptor_gain	0.9900
9:37588934:T:C	acceptor_gain	0.9900
9:37588934:T:G	acceptor_gain	0.9900
9:37592293:T:A	donor_gain	0.9900
9:37592408:TCA:T	donor_loss	0.9900

AlphaMissense

329 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:37592414:A:T	V40D	0.990
9:37592440:A:C	F31L	0.990
9:37592440:A:T	F31L	0.990
9:37592442:A:G	F31L	0.990
9:37592423:A:T	L37H	0.985
9:37592441:A:G	F31S	0.985
9:37592426:G:T	A36D	0.983
9:37588920:A:G	L45S	0.982
9:37592423:A:C	L37R	0.981
9:37592473:C:A	M20I	0.981
9:37592473:C:G	M20I	0.981
9:37592473:C:T	M20I	0.981
9:37592438:A:C	L32R	0.977
9:37592482:T:A	K17N	0.977
9:37592482:T:G	K17N	0.977
9:37592438:A:T	L32H	0.976
9:37592450:A:T	I28K	0.974
9:37592438:A:G	L32P	0.973
9:37592528:A:G	F2S	0.973
9:37592423:A:G	L37P	0.967
9:37592466:C:G	D23H	0.967
9:37592420:A:T	L38Q	0.965
9:37588923:A:T	I44N	0.964
9:37588911:A:G	L48S	0.962
9:37592450:A:C	I28R	0.962
9:37592483:T:A	K17I	0.962
9:37592429:A:T	V35E	0.961
9:37588929:G:T	P42Q	0.959
9:37592465:T:A	D23V	0.955
9:37592454:A:G	S27P	0.953

dbSNP variants (sampled 300 via entrez): RS1001020310 (9:37590632 T>C), RS1001055087 (9:37590039 T>G), RS1001355089 (9:37590302 G>C), RS1001585147 (9:37591910 C>A), RS1001649974 (9:37591649 G>A), RS1002104793 (9:37589887 C>T), RS1002165248 (9:37589470 AC>A), RS1002623280 (9:37593130 C>A), RS1002633474 (9:37592860 C>G), RS1003149855 (9:37594422 G>A), RS1004494903 (9:37589805 A>C), RS1005020013 (9:37591032 G>A), RS1005401712 (9:37591107 A>C,G), RS1005463983 (9:37589402 T>C), RS1005464076 (9:37591562 C>A,T)

Disease associations

OMIM: gene MIM:616169 | 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
GCST004963_5	Lipoprotein phospholipase A2 activity in cardiovascular disease	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	5
Valproic Acid	affects cotreatment, increases expression, affects expression	5
bisphenol A	affects expression, decreases expression	2
arsenite	affects binding, increases reaction, increases methylation	2
chloropicrin	affects expression, decreases expression	2
Tretinoin	increases expression, decreases expression, affects cotreatment	2
methylmercuric chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases 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, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Dimethyl Sulfoxide	affects expression	1
Doxorubicin	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Oxygen	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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