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
• GTEx eGene: eQTL in 32 tissues, sQTL in 1 (q < 0.05)
• Cancer dependency (DepMap): dependent in 89.7% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.52 (unconstrained)
• 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: 13 — 13 protein_coding

MANE Select: ENST00000215570

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 1

ENST00000215570, ENST00000591871, ENST00000853530, ENST00000853531, ENST00000853532, ENST00000853533, ENST00000939024, ENST00000939025, ENST00000939026, ENST00000939027, ENST00000939028, ENST00001034983, ENST00001135590

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.

Highest expression (Bgee): mucosa of transverse colon, apex of heart, lower esophagus mucosa, adrenal gland, adrenal gland cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TIMM13 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 32 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 33 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	1.9e-64	-0.35	19:2426830:G:C
Skin Sun Exposed Lower leg	eqtl	7.8e-47	-0.25	19:2426830:G:C
Skin Not Sun Exposed Suprapubic	eqtl	2.6e-37	-0.27	19:2426830:G:C
Brain Cortex	eqtl	2.3e-27	+0.44	19:2426830:G:C
Thyroid	eqtl	8.1e-27	+0.19	19:2426830:G:C
Brain Frontal Cortex BA9	eqtl	8.7e-26	+0.40	19:2426830:G:C
Cells Cultured fibroblasts	eqtl	3.0e-22	-0.30	19:2410444:G:A
Brain Hypothalamus	eqtl	4.9e-22	+0.45	19:2426830:G:C
Brain Caudate basal ganglia	eqtl	1.3e-18	+0.27	19:2426830:G:C
Brain Nucleus accumbens basal ganglia	eqtl	4.0e-18	+0.30	19:2426830:G:C
Brain Anterior cingulate cortex BA24	eqtl	1.4e-15	+0.34	19:2426830:G:C
Pancreas	eqtl	3.2e-14	-0.31	19:2421223:T:C
Brain Cerebellar Hemisphere	eqtl	6.1e-13	+0.23	19:2426830:G:C
Brain Putamen basal ganglia	eqtl	6.4e-13	+0.28	19:2426830:G:C
Liver	eqtl	1.9e-12	-0.29	19:2398226:A:G
Heart Atrial Appendage	eqtl	2.0e-11	+0.17	19:2449945:T:C
Pituitary	eqtl	1.8e-10	+0.27	19:2421223:T:C
Brain Cerebellum	eqtl	9.7e-10	+0.30	19:2426830:G:C
Brain Hippocampus	eqtl	8.4e-09	+0.23	19:2426830:G:C
Whole Blood	eqtl	1.0e-08	+0.21	19:2418033:C:T

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

showing 100 of 141 tissues 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
amygdala	UBERON:0001876	94.28	gold quality
hypothalamus	UBERON:0001898	94.27	gold quality
Ammon’s horn	UBERON:0001954	94.20	gold quality
stromal cell of endometrium	CL:0002255	94.19	gold quality
cerebral cortex	UBERON:0000956	94.18	gold quality
anterior cingulate cortex	UBERON:0009835	94.09	gold quality
duodenum	UBERON:0002114	94.05	gold quality
heart	UBERON:0000948	93.97	gold quality
esophagus	UBERON:0001043	93.93	gold quality
fundus of stomach	UBERON:0001160	93.93	gold quality
primary visual cortex	UBERON:0002436	93.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.85	gold quality
left testis	UBERON:0004533	93.83	gold quality
right testis	UBERON:0004534	93.82	gold quality
putamen	UBERON:0001874	93.67	gold quality
right frontal lobe	UBERON:0002810	93.63	gold quality
left lobe of thyroid gland	UBERON:0001120	93.60	gold quality
omental fat pad	UBERON:0010414	93.59	gold quality
prostate gland	UBERON:0002367	93.57	gold quality
right lobe of thyroid gland	UBERON:0001119	93.54	gold quality
spleen	UBERON:0002106	93.52	gold quality
pituitary gland	UBERON:0000007	93.51	gold quality
right ovary	UBERON:0002118	93.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.43	gold quality
brain	UBERON:0000955	93.41	gold quality
left ovary	UBERON:0002119	93.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.33	gold quality
nucleus accumbens	UBERON:0001882	93.32	gold quality
vagina	UBERON:0000996	93.31	gold quality
liver	UBERON:0002107	93.27	gold quality
right uterine tube	UBERON:0001302	93.22	gold quality
adenohypophysis	UBERON:0002196	93.21	gold quality
placenta	UBERON:0001987	93.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.15	gold quality
minor salivary gland	UBERON:0001830	93.15	gold quality
saliva-secreting gland	UBERON:0001044	93.09	gold quality
ganglionic eminence	UBERON:0004023	93.04	gold quality
embryo	UBERON:0000922	93.03	gold quality
colon	UBERON:0001155	93.01	gold quality
kidney	UBERON:0002113	92.92	gold quality
ventricular zone	UBERON:0003053	92.88	gold quality
caudate nucleus	UBERON:0001873	92.87	gold quality
cortical plate	UBERON:0005343	92.87	gold quality
thyroid gland	UBERON:0002046	92.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.84	gold quality
stomach	UBERON:0000945	92.82	gold quality
ovary	UBERON:0000992	92.80	gold quality
testis	UBERON:0000473	92.79	gold quality
adipose tissue	UBERON:0001013	92.49	gold quality
superior frontal gyrus	UBERON:0002661	92.43	gold quality
small intestine	UBERON:0002108	92.39	gold quality
left coronary artery	UBERON:0001626	92.37	gold quality
intestine	UBERON:0000160	92.25	gold quality
lower esophagus	UBERON:0013473	92.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.23	gold quality
anatomical system	UBERON:0000467	92.21	gold quality
material anatomical entity	UBERON:0000465	92.20	gold quality
multicellular organism	UBERON:0000468	92.20	gold quality
left uterine tube	UBERON:0001303	92.15	gold quality
ectocervix	UBERON:0012249	92.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.08	gold quality
granulocyte	CL:0000094	92.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.98	gold quality
thoracic mammary gland	UBERON:0005200	91.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.92	gold quality
upper lobe of left lung	UBERON:0008952	91.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.70	gold quality
endocervix	UBERON:0000458	91.57	gold quality
tibial nerve	UBERON:0001323	91.16	gold quality
cerebellum	UBERON:0002037	91.15	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	111.9
Caudate putamen	tissue	97.5
Skeletal muscle	tissue	71.8	not detected
Vagina	tissue	55.7	medium
Pancreas	tissue	55.3	medium
Pituitary gland	tissue	49.5
Locus coeruleus	tissue	49.2
Choroid plexus	tissue	48.1
Duodenum	tissue	48.0	medium
Hippocampus	tissue	40.5	low
Tongue	tissue	39.5
Small intestine	tissue	39.2	medium
Adrenal gland	tissue	38.0	high
Nucleus accumbens	tissue	37.1
Ovary	tissue	36.9	not detected
Salivary gland	tissue	36.7	medium
Bone marrow	tissue	32.5	not detected
Parathyroid gland	tissue	30.4	medium
Colon	tissue	29.7	medium
Postcentral gyrus	tissue	29.3
Stomach 1	tissue	28.9	high
Thymus	tissue	28.9
Liver	tissue	25.8	medium
Heart muscle	tissue	25.1	medium
Appendix	tissue	25.1	medium
Lymph node	tissue	24.8	medium
Kidney	tissue	24.7	high
Placenta	tissue	23.4	medium
Spleen	tissue	22.7	medium
Skin 1	tissue	22.1	medium
Esophagus	tissue	21.6	high
Urinary bladder	tissue	20.8	medium
Adipose tissue	tissue	20.5	not detected
Prostate	tissue	19.0	medium
Fallopian tube	tissue	17.8	medium
Testis	tissue	17.0	high
Rectum	tissue	15.4	medium
Gallbladder	tissue	14.8	medium
Tonsil	tissue	14.6	medium
Thyroid gland	tissue	14.3	medium
Endometrium 1	tissue	13.3	medium
Breast	tissue	13.1	high
Lung	tissue	12.7	not detected
Seminal vesicle	tissue	11.4	medium
Smooth muscle	tissue	10.9	low
Corpus callosum	tissue	10.8
Cerebral cortex	tissue	10.7	medium
Epididymis	tissue	10.7	medium
Medulla oblongata	tissue	10.7
Temporal cortex	tissue	10.7
Basal ganglia	tissue	10.6	medium
Putamen	tissue	10.6
Hippocampal formation	tissue	10.6
Insular cortex	tissue	10.6
Pons	tissue	10.5
Amygdala	tissue	10.5
Spinal cord	tissue	10.5
Septum	tissue	10.5
Retrosplenial cortex	tissue	10.5
Ventral forebrain	tissue	10.4

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Posterior thalamic nucleus (57.9), Periaquaductal grey, anterior (51.3), Lateral geniculate body (51.1), Cerebellar nuclei (50.4), Nucleus ambiguus (49.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TIMM13 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 38 miRNAs:

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

gnomAD constraint: pLI 0.00232, LOEUF 1.52, missense Z -0.383 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000215570 — one region, missense o/e 1.11. DepMap (CRISPR cell-line fitness): dependent in 89.7% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): HPAF-II (-2.044), SF-295 (-1.899), SU-DHL-10 (-1.816), AU565 (-1.81), COLO-800 (-1.744), PANC-1 (-1.737), KE-37 (-1.717), RH-41 (-1.655), HCC1143 (-1.655), NCI-H1944 (-1.653), KELLY (-1.647), JVM-3 (-1.607), SLR 20 (-1.604), G-401 (-1.586), NCI-H82 (-1.581).

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1353432) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal liver morphology	1
abnormal spleen morphology	1
enlarged thymus	1
abnormal seminal vesicle morphology	1
small uterus	1
enlarged kidney	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1
abnormal freezing behavior	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cryptococcus deneoformans JEC21	P0CS00	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CS01	100.0%	Diamond
Bos taurus	Q3ZBS8	99.0%	Diamond
Xenopus laevis	Q6GPY0	95.8%	Diamond
Takifugu rubripes	Q90YI5	87.8%	Diamond
Debaryomyces hansenii CBS767	Q6BN23	79.3%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CJX3	74.8%	Diamond
Eremothecium gossypii ATCC 10895	Q75F72	74.8%	Diamond
Nakaseomyces glabratus CBS 138	Q6FRE1	70.0%	Diamond
Saccharomyces cerevisiae S288C	P53299	68.8%	Diamond
Brugia malayi	Q9Y193	66.3%	Diamond
Candida albicans SC5314	Q5AF54	63.9%	Diamond
Neurospora crassa OR74A	Q7SBR3	61.0%	Diamond
Fusarium graminearum PH-1	Q4I6B0	60.2%	Diamond
Aspergillus fumigatus Af293	Q4X0V2	56.8%	Diamond
Aspergillus nidulans FGSC A4	Q5AZH4	53.8%	Diamond
Schizosaccharomyces pombe 972h-	Q10481	53.3%	Diamond
Oryza sativa Japonica Group	Q9XGY5	53.2%	Diamond
Mycosarcoma maydis	Q4PGT2	50.7%	Diamond
Arabidopsis thaliana	Q9XH48	49.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR7108	ncRNA	102466806
TMPRSS9	protein-coding	360200
GADD45B	protein-coding	4616
LMNB2	protein-coding	84823
LINC01775	ncRNA	101928602
SPPL2B	protein-coding	56928
LSM7	protein-coding	51690
PEAK3	protein-coding	374872
LINGO3	protein-coding	645191

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nucleoli fibrillar center

Antibody reliability (HPA): IH uncertain · IF supported

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)

Type	Positions
N-acetylmethionine	1
Phosphoserine	7
N6-succinyllysine	53

Disulfide bonds (2)

Type	Positions
Disulfide bond	46–69, 50–65

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 2; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

2 pathways:

ID	Pathway	Evidence
R-HSA-1268020	Mitochondrial protein import	electronic
R-HSA-9609507	Protein localization	—

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 (3): 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 (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial intermembrane space chaperone complex (GO:0042719)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Protein localization	1

GO top-level categories

17 GO namespaces:

Category	Terms
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
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
protein insertion into mitochondrial inner membrane	BP	mutant phenotype
mitochondrial inner membrane	CC	direct assay
mitochondrial intermembrane space chaperone complex	CC	physical interaction
mitochondrion	CC	direct assay

Protein interactions and networks

IntAct

Human interaction partners of TIMM13 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
TIMM8A	physical association	0.740	3
USHBP1	physical association	0.560	3
MAPT	proximity	0.420	1
ADRM1	physical association	0.400	1
CDC34	physical association	0.370	1
KLF11	physical association	0.370	1
OARD1	association	0.350	1
CAB39	physical association	0.000	1
CUL2	physical association	0.000	1
EPB41	physical association	0.000	1
HLA-B	physical association	0.000	1
MOB4	physical association	0.000	1
RAD51	physical association	0.000	1
RPA3	physical association	0.000	1
TIMM8B	physical association	0.000	1

BioGRID (223 interactions; top human partners by supporting records): TIMM8A (Co-fractionation; 5 records), TIMM8B (Co-fractionation; 5 records), AIFM1 (Proximity Label-MS; 3 records), MAP3K14 (Affinity Capture-MS; 3 records), PDYN (Affinity Capture-MS; 3 records), TUBG1 (Affinity Capture-MS; 3 records), C9orf173 (Affinity Capture-MS; 2 records), COX4I1 (Proximity Label-MS; 2 records), CUL3 (Affinity Capture-MS; 2 records), FGFR3 (Affinity Capture-MS; 2 records), HIST1H4A (Affinity Capture-MS; 2 records), HSF4 (Affinity Capture-Luminescence; 2 records), SFXN1 (Proximity Label-MS; 2 records), SOCS2 (Affinity Capture-MS; 2 records), SOCS6 (Proximity Label-MS; 2 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
TIMM13	“form complex”	“TIM8A-TIM13 mitochondrial intermembrane space protein transporter complex”	binding
TIMM13	“form complex”	“TIM8B-TIM13 mitochondrial intermembrane space protein transporter complex”	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
TIMM8A-TIMM13 complex, mitochondrial	2	TIMM13, TIMM8A

Disease & clinical

Genetic variants

Variant evidence for TIMM13: 25 ClinVar records (0 pathogenic / likely pathogenic).

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 122):

Position(s)	Effect	Δscore	Sites
19:2427047	acceptor_loss	1.0000
19:2427254–2427255	donor_loss	1.0000	4
19:2427412–2427413	donor_loss	1.0000	4
19:2427047–2427048	acceptor_loss	0.9900	5
19:2427254	donor_loss	0.9900
19:2427325–2427326	acceptor_loss	0.9900	6
19:2427413	donor_loss	0.9900
19:2427327	acceptor_loss	0.9800
19:2427057	acceptor_gain	0.9700
19:2427416	donor_gain	0.9600

AlphaMissense

389 missense substitutions predicted likely pathogenic (of 628 scored), across 80 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M70	9	0.915	0.991
D71	8	0.989	0.999
D75	8	0.964	0.997
D59	8	0.926	0.993
N78	8	0.862	0.986
M42	8	0.798	0.998
C46	7	0.998	1.000
F47	7	0.998	0.999
C50	7	0.998	1.000
C65	7	0.997	0.999
C69	7	0.996	1.000
W77	7	0.992	0.998
E62	7	0.950	0.998
M74	7	0.922	0.992
Q36	7	0.903	0.999
M68	7	0.891	0.975
N34	7	0.883	0.992
E91	7	0.874	0.990
E37	7	0.873	0.989
R72	6	0.996	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	8.36e-08
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000463

Disease associations

OMIM: gene MIM:607383 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066276 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	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	affects cotreatment, decreases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TIMM13 across ~30M SureChEMBL compounds — explore on Sugi Predict.