TIMM13

Summary

TIMM13 (translocase of inner mitochondrial membrane 13, HGNC:11816) is a protein-coding gene on chromosome 19p13.3, encoding Mitochondrial import inner membrane translocase subunit Tim13 (Q9Y5L4). Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. It is a selective cancer dependency (DepMap: 89.7% of cell lines).

This gene encodes a member of the evolutionarily conserved TIMM (translocase of inner mitochondrial membrane) family of proteins that function as chaperones in the import of proteins from the cytoplasm into the mitochondrial inner membrane. Proteins of this family play a role in collecting substrate proteins from the translocase of the outer mitochondrial membrane (TOM) complex and delivering them to either the sorting and assembly machinery in the outer mitochondrial membrane (SAM) complex or the TIMM22 complex in the inner mitochondrial membrane. The encoded protein and the translocase of mitochondrial inner membrane 8a protein form a 70 kDa complex in the intermembrane space.

Source: NCBI Gene 26517 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 89.7% of screened cell lines
• MANE Select transcript: NM_012458

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11816
Approved symbol	TIMM13
Name	translocase of inner mitochondrial membrane 13
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Tim13
Ensembl gene	ENSG00000099800
Ensembl biotype	protein_coding
OMIM	607383
Entrez	26517

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000215570, ENST00000591871, ENST00000853530, ENST00000853531, ENST00000853532, ENST00000853533, ENST00000939024, ENST00000939025, ENST00000939026, ENST00000939027, ENST00000939028

RefSeq mRNA: 1 — MANE Select: NM_012458 NM_012458

CCDS: CCDS12089

Canonical transcript exons

ENST00000215570 — 3 exons

Exon	Start	End
ENSE00000655658	2427256	2427324
ENSE00001052192	2425625	2427046
ENSE00001307687	2427414	2427586

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 93.0342 / max 402.4467, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178166	83.0790	1823
178168	9.8399	1783
178167	0.1153	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.96	gold quality
apex of heart	UBERON:0002098	97.22	gold quality
lower esophagus mucosa	UBERON:0035834	97.22	gold quality
right adrenal gland	UBERON:0001233	96.94	gold quality
right adrenal gland cortex	UBERON:0035827	96.81	gold quality
left adrenal gland	UBERON:0001234	96.79	gold quality
left adrenal gland cortex	UBERON:0035825	96.71	gold quality
right lobe of liver	UBERON:0001114	96.20	gold quality
prefrontal cortex	UBERON:0000451	96.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.07	gold quality
esophagus mucosa	UBERON:0002469	95.94	gold quality
body of pancreas	UBERON:0001150	95.87	gold quality
cortex of kidney	UBERON:0001225	95.82	gold quality
metanephros cortex	UBERON:0010533	95.57	gold quality
adrenal gland	UBERON:0002369	95.44	gold quality
adult mammalian kidney	UBERON:0000082	95.43	gold quality
heart left ventricle	UBERON:0002084	95.09	gold quality
transverse colon	UBERON:0001157	94.97	gold quality
body of stomach	UBERON:0001161	94.95	gold quality
frontal cortex	UBERON:0001870	94.89	gold quality
frontal lobe	UBERON:0016525	94.89	gold quality
substantia nigra	UBERON:0002038	94.87	gold quality
skin of abdomen	UBERON:0001416	94.83	gold quality
gastrocnemius	UBERON:0001388	94.76	gold quality
skin of leg	UBERON:0001511	94.63	gold quality
right atrium auricular region	UBERON:0006631	94.63	gold quality
zone of skin	UBERON:0000014	94.51	gold quality
muscle of leg	UBERON:0001383	94.49	gold quality
muscle organ	UBERON:0001630	94.35	gold quality
temporal lobe	UBERON:0001871	94.32	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	138.35
E-CURD-122	yes	20.20
E-ANND-3	yes	14.95
E-MTAB-6075	no	329.02
E-MTAB-7249	no	190.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting TIMM13, 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-4283	100.00	66.42	2097
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4796-5P	99.34	70.06	810
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-483-3P	97.77	64.95	731
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-6783-5P	97.67	67.21	1528

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 89.7% of screened cell lines.

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	timm13	ENSDARG00000058297
mus_musculus	Timm13	ENSMUSG00000020219
rattus_norvegicus	Timm13	ENSRNOG00000019682
drosophila_melanogaster	Tim13	FBGN0036204
drosophila_melanogaster	CG34132	FBGN0083968
drosophila_melanogaster	CG42302	FBGN0259198
caenorhabditis_elegans	tin-13	WBGENE00006574

Protein

Protein identifiers

Mitochondrial import inner membrane translocase subunit Tim13 — Q9Y5L4 (reviewed: Q9Y5L4)

All UniProt accessions (2): Q9Y5L4, K7EIT2

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins.

Subunit / interactions. Heterohexamer; composed of 3 copies of TIMM8 (TIMM8A or TIMM8B) and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Ubiquitous, with highest expression in heart, kidney, liver and skeletal muscle.

Domain organisation. The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane.

Similarity. Belongs to the small Tim family.

RefSeq proteins (1): NP_036590* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004217	Tim10-like	Domain
IPR035427	Tim10-like_dom_sf	Homologous_superfamily

Pfam: PF02953

UniProt features (10 total): modified residue 3, sequence conflict 3, disulfide bond 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5L4-F1	85.14	0.61

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 (3): 1, 7, 53

Disulfide bonds (2): 46–69, 50–65

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import

MSigDB gene sets: 139 (showing top): GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_SENSORY_PERCEPTION, WONG_MITOCHONDRIA_GENE_MODULE, GOBP_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_PROTEIN_TARGETING_TO_MITOCHONDRION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, CUI_TCF21_TARGETS_2_UP

GO Biological Process (4): obsolete protein targeting to mitochondrion (GO:0006626), sensory perception of sound (GO:0007605), protein transport (GO:0015031), protein insertion into mitochondrial inner membrane (GO:0045039)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): fibrillar center (GO:0001650), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial intermembrane space chaperone complex (GO:0042719), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
sensory perception of mechanical stimulus	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
inner mitochondrial membrane organization	1
mitochondrial protein import pathway	1
transition metal ion binding	1
binding	1
cation binding	1
nucleolus	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrial intermembrane space	1
mitochondrial protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

148 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
AFG2B	AFG2A	psi-mi:“MI:0914”(association)	0.800
EZR	MSN	psi-mi:“MI:0914”(association)	0.740
TIMM8A	TIMM13	psi-mi:“MI:0915”(physical association)	0.740
TIMM8A	TIMM13	psi-mi:“MI:0407”(direct interaction)	0.740
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
LLGL1	DNAJA2	psi-mi:“MI:0914”(association)	0.640
USHBP1	TIMM13	psi-mi:“MI:0915”(physical association)	0.560
PDYN	ACAD11	psi-mi:“MI:0914”(association)	0.530
YBEY	NME4	psi-mi:“MI:0914”(association)	0.530
HSF4	HSF1	psi-mi:“MI:0914”(association)	0.530
env	PGRMC1	psi-mi:“MI:0914”(association)	0.460
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
AIFM1	HAX1	psi-mi:“MI:2364”(proximity)	0.420
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
MAPT	TIMM13	psi-mi:“MI:2364”(proximity)	0.420
ADRM1	TIMM13	psi-mi:“MI:0915”(physical association)	0.400
CDC34	TIMM13	psi-mi:“MI:0915”(physical association)	0.370
TIMM13	KLF11	psi-mi:“MI:0915”(physical association)	0.370
YWHAZ	WDR62	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MATR3	BCLAF3	psi-mi:“MI:0914”(association)	0.350
DBN1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TUBG1	DPM1	psi-mi:“MI:0914”(association)	0.350
GPATCH8	FDX1	psi-mi:“MI:0914”(association)	0.350
Myo1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Kif3c	ARPC1B	psi-mi:“MI:0914”(association)	0.350

BioGRID (218): TIMM13 (Affinity Capture-MS), TIMM13 (Affinity Capture-MS), MIF (Co-fractionation), NDRG1 (Co-fractionation), TIMM10 (Co-fractionation), TIMM13 (Co-fractionation), TIMM13 (Co-fractionation), TIMM13 (Co-fractionation), TIMM8A (Co-fractionation), TIMM8B (Co-fractionation), TIMM13 (Affinity Capture-MS), ALB (Affinity Capture-MS), BPTF (Affinity Capture-MS), BCL7C (Affinity Capture-MS), VPRBP (Affinity Capture-MS)

ESM2 similar proteins: A4QNC6, B0BN94, O74700, P0CR96, P0CR97, P0CS00, P0CS01, P30629, P62075, P62076, P62077, P62078, Q10481, Q2HJI3, Q2KIV2, Q3SZ93, Q4I6B0, Q4V7R1, Q59MI8, Q59R24, Q5ZIR8, Q616Q2, Q61TH2, Q63ZH8, Q66L32, Q6BN23, Q6BU42, Q6CM57, Q6DEM5, Q6DGJ3, Q6FK81, Q6GPY0, Q6PBU0, Q75DU7, Q7SBR3, Q8AVK1, Q90YI5, Q96C01, Q9CR98, Q9N408

Diamond homologs: O45319, P0CS00, P0CS01, P53299, P62075, P62076, Q10481, Q4I6B0, Q4PGT2, Q4X0V2, Q5AF54, Q5AZH4, Q6CJX3, Q6DGJ3, Q6FRE1, Q6GPY0, Q75F72, Q8AVK1, Q9VTN3, Q9XGY5, Q9Y193, Q9Y5L4, O60220, P0CR94, P0CR95, P57744, P62077, P62078, Q3SZ93, Q3ZBS8, Q4FZG7, Q59MI8, Q616Q2, Q66L32, Q6BN23, Q6CWH5, Q6DEM5, Q6FK81, Q75DU7, Q90YI5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 180 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
Activation of NF-kappaB in B cells	6	9.8×	6e-03
CLEC7A (Dectin-1) signaling	8	9.5×	1e-03
FCERI mediated NF-kB activation	7	9.1×	3e-03
Mitochondrial protein degradation	8	7.6×	3e-03
Downstream TCR signaling	7	7.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

314 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2427042:CACTT:C	acceptor_gain	1.0000
19:2427044:CTT:C	acceptor_gain	1.0000
19:2427045:TT:T	acceptor_gain	1.0000
19:2427046:TC:T	acceptor_loss	1.0000
19:2427047:C:CC	acceptor_gain	1.0000
19:2427047:CTGC:C	acceptor_loss	1.0000
19:2427251:CTCA:C	donor_loss	1.0000
19:2427252:TCACC:T	donor_loss	1.0000
19:2427253:CACCT:C	donor_loss	1.0000
19:2427255:C:A	donor_loss	1.0000
19:2427321:TCCT:T	acceptor_gain	1.0000
19:2427322:CCTC:C	acceptor_gain	1.0000
19:2427323:CT:C	acceptor_gain	1.0000
19:2427325:C:CC	acceptor_gain	1.0000
19:2427408:CCGCA:C	donor_loss	1.0000
19:2427409:CGCAC:C	donor_loss	1.0000
19:2427411:CACC:C	donor_loss	1.0000
19:2425922:AACAG:A	acceptor_gain	0.9900
19:2425925:AG:A	acceptor_gain	0.9900
19:2425926:GG:G	acceptor_gain	0.9900
19:2427255:CCTG:C	donor_gain	0.9900
19:2427320:ATCCT:A	acceptor_gain	0.9900
19:2427322:CCTCT:C	acceptor_loss	0.9900
19:2427324:TC:T	acceptor_loss	0.9900
19:2425921:CAACA:C	acceptor_loss	0.9800
19:2425924:CA:C	acceptor_loss	0.9800
19:2425925:A:G	acceptor_loss	0.9800
19:2425926:G:GA	acceptor_loss	0.9800
19:2425926:GGGT:G	acceptor_gain	0.9800
19:2427056:C:CT	acceptor_gain	0.9800

AlphaMissense

628 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2426995:A:G	S81P	1.000
19:2427010:C:G	A76P	1.000
19:2427021:C:G	R72P	1.000
19:2427030:C:T	C69Y	1.000
19:2427297:A:G	C50R	1.000
19:2427307:A:C	C46W	1.000
19:2427308:C:A	C46F	1.000
19:2427308:C:T	C46Y	1.000
19:2427309:A:G	C46R	1.000
19:2427431:C:G	A35P	1.000
19:2427437:C:G	A33P	1.000
19:2427443:C:G	A31P	1.000
19:2426989:C:G	A83P	0.999
19:2426997:A:T	V80E	0.999
19:2427009:G:T	A76D	0.999
19:2427022:G:T	R72S	0.999
19:2427025:C:G	D71H	0.999
19:2427029:G:C	C69W	0.999
19:2427030:C:A	C69F	0.999
19:2427031:A:G	C69R	0.999
19:2427037:C:G	A67P	0.999
19:2427041:G:C	C65W	0.999
19:2427042:C:G	C65S	0.999
19:2427042:C:T	C65Y	0.999
19:2427043:A:G	C65R	0.999
19:2427043:A:T	C65S	0.999
19:2427295:A:C	C50W	0.999
19:2427296:C:A	C50F	0.999
19:2427296:C:G	C50S	0.999
19:2427296:C:T	C50Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000223929 (19:2429542 G>A), RS1000857314 (19:2427309 A>C), RS1002500540 (19:2426291 G>A,C), RS1002516479 (19:2429450 G>A), RS1002591426 (19:2429574 C>T), RS1002743096 (19:2425568 C>A,G,T), RS1003102569 (19:2425749 G>A,C), RS1003521548 (19:2427997 GA>G,GAA), RS1004210887 (19:2425472 G>A,C), RS1005208420 (19:2425975 G>A,C), RS1005538231 (19:2426551 T>C), RS1005714531 (19:2425737 G>A,C,T), RS1006309620 (19:2426616 G>A), RS1006547208 (19:2425820 G>A), RS1006627162 (19:2426798 C>A,T)

Disease associations

OMIM: gene MIM:607383 | 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: yes

ChEMBL targets (1): CHEMBL6066276 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment	3
Tretinoin	decreases expression	2
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	decreases expression	1
pinosylvin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	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	decreases expression, affects cotreatment	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Amiodarone	increases expression	1
Arsenic	decreases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	increases expression	1
Fonofos	increases methylation	1
Ethyl Methanesulfonate	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Parathion	increases methylation	1
Piroxicam	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652630	Binding	Binding affinity to human TIMM13 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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