TOMM40L

Summary

TOMM40L (translocase of outer mitochondrial membrane 40 like, HGNC:25756) is a protein-coding gene on chromosome 1q23.3, encoding Mitochondrial import receptor subunit TOM40B (Q969M1). Potential channel-forming protein implicated in import of protein precursors into mitochondria.

Predicted to enable protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Located in mitochondrion. Part of protein-containing complex.

Source: NCBI Gene 84134 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_032174

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25756
Approved symbol	TOMM40L
Name	translocase of outer mitochondrial membrane 40 like
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12770, TOMM40B
Ensembl gene	ENSG00000158882
Ensembl biotype	protein_coding
Entrez	84134

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000367987, ENST00000367988, ENST00000465512, ENST00000468803, ENST00000470426, ENST00000474486, ENST00000475793, ENST00000492482, ENST00000545897, ENST00000904816, ENST00000904817, ENST00000904818, ENST00000904819, ENST00000904820, ENST00000911458, ENST00000951901, ENST00000951902

RefSeq mRNA: 3 — MANE Select: NM_032174 NM_001286373, NM_001286374, NM_032174

CCDS: CCDS1227, CCDS65700

Canonical transcript exons

ENST00000367988 — 10 exons

Exon	Start	End
ENSE00001205354	161226060	161226136
ENSE00001845974	161228956	161230746
ENSE00003482445	161228715	161228817
ENSE00003498713	161228428	161228504
ENSE00003500977	161228186	161228308
ENSE00003583099	161227258	161227350
ENSE00003624253	161226888	161226955
ENSE00003633255	161227636	161227737
ENSE00003649346	161226355	161226604
ENSE00003663480	161227884	161227989

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 92.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.2520 / max 99.5005, expressed in 1656 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6239	5.8681	1636
6238	0.3839	191

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	92.97	gold quality
apex of heart	UBERON:0002098	91.77	gold quality
right lobe of liver	UBERON:0001114	91.28	gold quality
heart left ventricle	UBERON:0002084	89.57	gold quality
cardiac ventricle	UBERON:0002082	89.33	gold quality
prefrontal cortex	UBERON:0000451	88.99	gold quality
right atrium auricular region	UBERON:0006631	88.53	gold quality
cardiac atrium	UBERON:0002081	88.20	gold quality
right frontal lobe	UBERON:0002810	87.98	gold quality
heart	UBERON:0000948	87.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.34	gold quality
myocardium	UBERON:0002349	87.17	silver quality
anterior cingulate cortex	UBERON:0009835	87.05	gold quality
mucosa of transverse colon	UBERON:0004991	86.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.73	gold quality
cortical plate	UBERON:0005343	86.69	gold quality
muscle of leg	UBERON:0001383	86.64	gold quality
gastrocnemius	UBERON:0001388	86.58	gold quality
frontal cortex	UBERON:0001870	86.44	gold quality
neocortex	UBERON:0001950	86.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.74	gold quality
vastus lateralis	UBERON:0001379	85.08	silver quality
cerebral cortex	UBERON:0000956	84.77	gold quality
middle temporal gyrus	UBERON:0002771	84.74	gold quality
heart right ventricle	UBERON:0002080	84.69	gold quality
bone marrow cell	CL:0002092	84.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	84.48	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.17	gold quality
quadriceps femoris	UBERON:0001377	83.65	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting TOMM40L, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-2355-5P	98.83	65.51	1589

Literature-anchored findings (GeneRIF, showing 1)

• APOEvarepsilon4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer’s Disease. (PMID:33016906)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tomm40l	ENSMUSG00000005674
rattus_norvegicus	Tomm40l	ENSRNOG00000003398
drosophila_melanogaster	Tom40	FBGN0016041
drosophila_melanogaster	tomboy40	FBGN0033074
caenorhabditis_elegans		WBGENE00007686

Paralogs (1): TOMM40 (ENSG00000130204)

Protein

Protein identifiers

Mitochondrial import receptor subunit TOM40B — Q969M1 (reviewed: Q969M1)

Alternative names: Protein TOMM40-like

All UniProt accessions (1): Q969M1

UniProt curated annotations — full annotation on UniProt →

Function. Potential channel-forming protein implicated in import of protein precursors into mitochondria.

Subunit / interactions. Forms part of the preprotein translocase of the outer mitochondrial membrane (TOM complex) containing TOMM22, TOMM40, TOMM40L and TOMM70. Interacts with mitochondrial targeting sequences.

Subcellular location. Mitochondrion outer membrane.

Similarity. Belongs to the Tom40 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969M1-1	1	yes
Q969M1-2	2

RefSeq proteins (3): NP_001273302, NP_001273303, NP_115550* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023614	Porin_dom_sf	Homologous_superfamily
IPR027246	Porin_Euk/Tom40	Family
IPR037930	Tom40	Family

Pfam: PF01459

UniProt features (5 total): region of interest 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969M1-F1	90.39	0.80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 129 (showing top): GGGNRMNNYCAT_UNKNOWN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GGGTGGRR_PAX4_03, YY1_Q6, GGCNKCCATNK_UNKNOWN, CCANNAGRKGGC_UNKNOWN, YY1_02, TCF11_01, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_TRANSMEMBRANE_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GGCNNMSMYNTTG_UNKNOWN, GOBP_PROTEIN_IMPORT_INTO_MITOCHONDRIAL_MATRIX

GO Biological Process (5): monoatomic ion transport (GO:0006811), protein import into mitochondrial matrix (GO:0030150), biological_process (GO:0008150), protein transport (GO:0015031), transmembrane transport (GO:0055085)

GO Molecular Function (3): transmembrane protein transporter activity (GO:0008320), porin activity (GO:0015288), molecular_function (GO:0003674)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial outer membrane translocase complex (GO:0005742), protein-containing complex (GO:0032991), pore complex (GO:0046930), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
protein transmembrane import into intracellular organelle	1
protein localization to mitochondrion	1
import into the mitochondrion	1
mitochondrial protein import pathway	1
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
wide pore channel activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
outer mitochondrial membrane protein complex	1
cellular_component	1
membrane protein complex	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOMM40L	TOMM22	Q9NS69	736
TOMM40L	TOMM5	Q8N4H5	576
TOMM40L	TOMM7	Q9P0U1	568
TOMM40L	NDUFS2	O75306	535
TOMM40L	TOMM70	O94826	518
TOMM40L	TIMM10	P62072	502
TOMM40L	TIMM9	Q9Y5J7	501
TOMM40L	TIMM8B	Q9Y5J9	477
TOMM40L	TIMM44	O43615	473
TOMM40L	TIMM23	O14925	473
TOMM40L	SAMM50	Q9Y512	458
TOMM40L	TIMM22	Q9Y584	440
TOMM40L	ZC3H8	Q8N5P1	439
TOMM40L	TIMM13	P62206	434
TOMM40L	TIMM50	Q3ZCQ8	434

IntAct

8 interactions, top by confidence:

A	B	Type	Score
TOMM22	TOMM40	psi-mi:“MI:0914”(association)	0.740
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
TOMM40L	RAB1B	psi-mi:“MI:0915”(physical association)	0.370
TOMM6	TOMM40	psi-mi:“MI:0914”(association)	0.350
TOMM7	AMY2A	psi-mi:“MI:0914”(association)	0.350
MTCH2	IPO5	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): TOMM40L (Affinity Capture-RNA), TOMM40L (Affinity Capture-RNA), TOMM40L (Affinity Capture-RNA), AFMID (Affinity Capture-MS), TOMM40L (Affinity Capture-MS), TOMM40L (Affinity Capture-MS), TOMM40L (Affinity Capture-MS), TOMM40L (Affinity Capture-MS), TOMM40L (Affinity Capture-MS), TOMM40L (Affinity Capture-MS), TOMM40L (Two-hybrid)

ESM2 similar proteins: A0A1S4A695, A0A6P7EFR0, A4F267, A6QR22, O97556, P07144, P21796, P42055, P42056, P45879, P45880, P50395, P50397, P50399, P62495, P62496, P62497, P62498, P68002, P68003, P81004, P81155, P82013, P86223, Q0VCK5, Q0VCX5, Q1W374, Q1W375, Q1W376, Q1W377, Q29380, Q5R4C7, Q5R7V4, Q5RCE1, Q5U2Q7, Q60930, Q60931, Q60932, Q61598, Q6Q7J2

Diamond homologs: A1Z6L1, A4F267, A6QR22, O96008, Q18090, Q1LZB5, Q61Z83, Q6P825, Q75Q40, Q7ZTM6, Q969M1, Q9CZR3, Q9QYA2, Q9U4L6, Q9LHE5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2083 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161226133:GATG:G	donor_gain	1.0000
1:161226474:A:AG	acceptor_gain	1.0000
1:161226475:G:GG	acceptor_gain	1.0000
1:161226601:AAAGG:A	donor_loss	1.0000
1:161226602:AAGG:A	donor_loss	1.0000
1:161226603:AGGTG:A	donor_loss	1.0000
1:161226604:GGTGA:G	donor_loss	1.0000
1:161226605:G:C	donor_loss	1.0000
1:161227721:C:G	donor_gain	1.0000
1:161227982:G:GT	donor_gain	1.0000
1:161228182:ACAGT:A	acceptor_gain	1.0000
1:161228183:CA:C	acceptor_loss	1.0000
1:161228184:A:AG	acceptor_gain	1.0000
1:161228184:AGT:A	acceptor_gain	1.0000
1:161228185:G:GT	acceptor_gain	1.0000
1:161228185:GT:G	acceptor_gain	1.0000
1:161228185:GTG:G	acceptor_gain	1.0000
1:161228185:GTGA:G	acceptor_gain	1.0000
1:161228185:GTGAT:G	acceptor_gain	1.0000
1:161228275:G:GT	donor_gain	1.0000
1:161228298:G:GT	donor_gain	1.0000
1:161228298:G:T	donor_gain	1.0000
1:161228301:G:GG	donor_gain	1.0000
1:161228306:CGG:C	donor_loss	1.0000
1:161228307:GG:G	donor_gain	1.0000
1:161228308:GG:G	donor_gain	1.0000
1:161228309:G:C	donor_loss	1.0000
1:161228310:T:A	donor_loss	1.0000
1:161228323:G:GT	donor_gain	1.0000
1:161228426:A:AG	acceptor_gain	1.0000

AlphaMissense

2001 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161228778:T:G	Y250D	0.998
1:161228478:A:C	S220R	0.997
1:161228480:T:A	S220R	0.997
1:161228480:T:G	S220R	0.997
1:161228481:T:G	Y221D	0.997
1:161228207:T:C	L169P	0.996
1:161228237:G:A	G179E	0.996
1:161228236:G:A	G179R	0.995
1:161228236:G:C	G179R	0.995
1:161228294:C:A	A198D	0.995
1:161228249:T:A	V183D	0.994
1:161228776:G:A	G249D	0.993
1:161228251:T:G	Y184D	0.992
1:161228817:G:C	G263R	0.992
1:161227684:G:C	A109P	0.991
1:161228458:G:A	G213E	0.991
1:161228475:G:C	A219P	0.991
1:161228722:T:A	V231D	0.991
1:161228725:G:A	G232E	0.991
1:161227947:G:C	A148P	0.990
1:161228237:G:T	G179V	0.990
1:161228246:T:C	L182P	0.990
1:161228302:T:G	Y201D	0.990
1:161228739:G:C	A237P	0.990
1:161228778:T:A	Y250N	0.990
1:161228956:G:A	G263D	0.990
1:161226569:C:A	P27H	0.989
1:161226602:A:T	K38I	0.989
1:161227945:C:A	T147K	0.989
1:161228476:C:A	A219E	0.989

dbSNP variants (sampled 300 via entrez): RS1000743440 (1:161230686 A>G), RS1000935000 (1:161228070 T>C), RS1002294447 (1:161227015 T>C), RS1002296489 (1:161226268 T>A,C,G), RS1002363263 (1:161227478 TGAGA>T,TGA), RS1002514058 (1:161225225 C>T), RS1003036836 (1:161224895 C>T), RS1003296079 (1:161228885 G>A,C), RS1004390814 (1:161230489 A>G), RS1004444571 (1:161230224 C>T), RS1004780405 (1:161228695 T>C), RS1004851301 (1:161225179 T>C), RS1006446654 (1:161227752 T>C), RS1006828059 (1:161226095 G>A), RS1008782647 (1:161224201 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3813627	APOA2, TOMM40L		0.00	0
rs3813628	TOMM40L		0.00	0
rs4073054	NR1I3, TOMM40L		0.00	0
rs2307418	NR1I3, TOMM40L		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	5
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	5
Acetaminophen	decreases expression	3
sodium arsenite	increases expression, decreases expression	2
GSK-J4	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pirinixic acid	affects binding, increases activity, increases expression	1
trichostatin A	affects expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
pentabromodiphenyl ether	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Copper	affects binding, decreases expression	1
Lead	affects methylation	1
Ozone	increases abundance, affects cotreatment, decreases expression	1
Phenobarbital	affects expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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