TIMM17A

Summary

TIMM17A (translocase of inner mitochondrial membrane 17A, HGNC:17315) is a protein-coding gene on chromosome 1q32.1, encoding Mitochondrial import inner membrane translocase subunit Tim17-A (Q99595). Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. It is a selective cancer dependency (DepMap: 18.5% of cell lines).

Predicted to contribute to protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Located in mitochondrial inner membrane and nucleoplasm. Part of TIM23 mitochondrial import inner membrane translocase complex.

Source: NCBI Gene 10440 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 18.5% of screened cell lines
• MANE Select transcript: NM_006335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17315
Approved symbol	TIMM17A
Name	translocase of inner mitochondrial membrane 17A
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	TIM17, TIM17A
Ensembl gene	ENSG00000134375
Ensembl biotype	protein_coding
OMIM	605057
Entrez	10440

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000367287, ENST00000478378, ENST00000482943, ENST00000484647, ENST00000880520, ENST00000880521, ENST00000880522, ENST00000934114, ENST00000955674

RefSeq mRNA: 1 — MANE Select: NM_006335 NM_006335

CCDS: CCDS1417

Canonical transcript exons

ENST00000367287 — 6 exons

Exon	Start	End
ENSE00001444069	201969469	201970664
ENSE00001444070	201955503	201955552
ENSE00003492217	201963616	201963744
ENSE00003535049	201957511	201957574
ENSE00003560786	201965433	201965543
ENSE00003592824	201957281	201957380

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.9349 / max 1617.6651, expressed in 1821 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7769	55.9349	1821

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.39	gold quality
heart right ventricle	UBERON:0002080	98.35	gold quality
biceps brachii	UBERON:0001507	98.20	gold quality
middle temporal gyrus	UBERON:0002771	98.15	gold quality
endothelial cell	CL:0000115	98.14	gold quality
orbitofrontal cortex	UBERON:0004167	97.96	gold quality
amniotic fluid	UBERON:0000173	97.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.72	gold quality
left ventricle myocardium	UBERON:0006566	97.70	gold quality
choroid plexus epithelium	UBERON:0003911	97.66	gold quality
nephron tubule	UBERON:0001231	97.46	gold quality
palpebral conjunctiva	UBERON:0001812	97.45	gold quality
parietal pleura	UBERON:0002400	97.42	gold quality
myocardium	UBERON:0002349	97.40	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.32	gold quality
epithelium of nasopharynx	UBERON:0001951	97.29	gold quality
pleura	UBERON:0000977	97.20	gold quality
visceral pleura	UBERON:0002401	97.14	gold quality
pons	UBERON:0000988	97.12	gold quality
vastus lateralis	UBERON:0001379	97.07	gold quality
oocyte	CL:0000023	97.04	gold quality
diaphragm	UBERON:0001103	96.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.92	gold quality
substantia nigra pars compacta	UBERON:0001965	96.90	gold quality
esophagus squamous epithelium	UBERON:0006920	96.89	gold quality
renal glomerulus	UBERON:0000074	96.86	gold quality
pigmented layer of retina	UBERON:0001782	96.80	gold quality
secondary oocyte	CL:0000655	96.79	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.77	gold quality
germinal epithelium of ovary	UBERON:0001304	96.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting TIMM17A, 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-3924	100.00	72.09	2394
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-1208	99.70	68.28	1533

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• Tim17 is a conserved suppressor of mtDNA instability. (PMID:18826960)
• mRNA expression analysis and immunohistochemistry analysis in breast cancer tissues indicated that expression level of TIMM17A was directly correlated with tumor progression; survival analysis suggested TIMM17A was a prognosis factor in breast cancer. (PMID:20198662)
• High TIMM17A expression is associated with adverse pathological outcomes in breast cancer. (PMID:20972741)
• TIMM17A has a profound impact on the cellular function of breast cancer cells. A decrease of TIMM17A expression is associated with the reduction of the aggressiveness of breast cancer cells. (PMID:26977020)
• We also confirmed that lncRNA NEAT1 was up-regulated in breast cancer and inhibited the expression of miR-133b, and identified the mitochondrial protein translocase of inner mitochondrial membrane 17 homolog A (TIMM17A) that serves as the target of miR-133b. (PMID:31344855)
• Tim17 Updates: A Comprehensive Review of an Ancient Mitochondrial Protein Translocator. (PMID:33297490)
• Central role of Tim17 in mitochondrial presequence protein translocation. (PMID:37527780)
• TIMM17A overexpression in lung adenocarcinoma and its association with prognosis. (PMID:38632467)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	timm17a	ENSDARG00000029510
mus_musculus	Timm17a	ENSMUSG00000062580
rattus_norvegicus	Timm17a	ENSRNOG00000007040
drosophila_melanogaster	Tim17b2	FBGN0020371
drosophila_melanogaster	CG1724	FBGN0031164
drosophila_melanogaster	Tim17a2	FBGN0037307
drosophila_melanogaster	Tim17b1	FBGN0037310
drosophila_melanogaster	Tim17a1	FBGN0038018
drosophila_melanogaster	Tim17b	FBGN0263977
caenorhabditis_elegans		WBGENE00017069
caenorhabditis_elegans		WBGENE00017119

Paralogs (1): TIMM17B (ENSG00000126768)

Protein

Protein identifiers

Mitochondrial import inner membrane translocase subunit Tim17-A — Q99595 (reviewed: Q99595)

Alternative names: Inner membrane preprotein translocase Tim17a

All UniProt accessions (1): Q99595

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.

Subunit / interactions. Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50. The complex interacts with the TIMM44 component of the PAM complex and with DNAJC15.

Subcellular location. Mitochondrion inner membrane.

Post-translational modifications. Degraded by YMEL1 downstream of the integrated stress response (ISR).

Similarity. Belongs to the Tim17/Tim22/Tim23 family.

RefSeq proteins (1): NP_006326* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005678	Tim17	Family

Pfam: PF02466

UniProt features (8 total): transmembrane region 3, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99595-F1	79.87	0.60

Functional residue map

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

Disulfide bonds (1): 9–78

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-392499	Metabolism of proteins
R-HSA-9609507	Protein localization

MSigDB gene sets: 206 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BASSO_B_LYMPHOCYTE_NETWORK, ENK_UV_RESPONSE_KERATINOCYTE_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, DITTMER_PTHLH_TARGETS_UP, GOBP_PROTEIN_TARGETING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, GCM_RING1, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GCM_DPF2

GO Biological Process (4): obsolete protein targeting to mitochondrion (GO:0006626), intracellular protein transport (GO:0006886), protein import into mitochondrial matrix (GO:0030150), protein transport (GO:0015031)

GO Molecular Function (1): transmembrane protein transporter activity (GO:0008320)

GO Cellular Component (5): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), TIM23 mitochondrial import inner membrane translocase complex (GO:0005744), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein localization	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	2
cellular anatomical structure	2
protein transport	1
intracellular transport	1
protein transmembrane import into intracellular organelle	1
protein localization to mitochondrion	1
import into the mitochondrion	1
mitochondrial protein import pathway	1
transport	1
establishment of protein localization	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1
protein transporter activity	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
inner mitochondrial membrane protein complex	1

Protein interactions and networks

STRING

1678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIMM17A	TIMM50	Q3ZCQ8	999
TIMM17A	TIMM44	O43615	997
TIMM17A	TIMM23	O14925	988
TIMM17A	TIMM21	Q9BVV7	983
TIMM17A	DNAJC19	Q96DA6	954
TIMM17A	TOMM70	O94826	944
TIMM17A	TIMM10	P62072	943
TIMM17A	PAM16	Q9Y3D7	932
TIMM17A	OXA1L	Q15070	923
TIMM17A	TOMM20	Q15388	922
TIMM17A	HSPA9	P30036	893
TIMM17A	GRPEL1	Q9HAV7	875
TIMM17A	TOMM22	Q9NS69	872
TIMM17A	TOMM40	O96008	865
TIMM17A	TIMM9	Q9Y5J7	807

IntAct

21 interactions, top by confidence:

A	B	Type	Score
ALDH3B2	ALDH3B1	psi-mi:“MI:0914”(association)	0.560
TUBA1A	TIMM17A	psi-mi:“MI:0915”(physical association)	0.370
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
DNAJC15	TIMM17B	psi-mi:“MI:0914”(association)	0.350
P2RX5	NOP56	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
GLMP	RTL8C	psi-mi:“MI:0914”(association)	0.350
P2RX5	TNPO2	psi-mi:“MI:0914”(association)	0.350
KLK8	MGST3	psi-mi:“MI:0914”(association)	0.350
APLNR	TTI1	psi-mi:“MI:0914”(association)	0.350
MAGEA8	B4GALT5	psi-mi:“MI:0914”(association)	0.350
SLC30A3	WWP2	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
AKT1	TIMM17A	psi-mi:“MI:2364”(proximity)	0.270
BRAF	TIMM17A	psi-mi:“MI:2364”(proximity)	0.270
VHL	TIMM17A	psi-mi:“MI:0915”(physical association)	0.000
TIMM17A	ROMO1	psi-mi:“MI:0915”(physical association)	0.000
TIMM17A	ELOVL5	psi-mi:“MI:0915”(physical association)	0.000
TIMM17A	HAP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): TIMM17A (Affinity Capture-Western), TIMM17A (Affinity Capture-Western), TIMM17A (Affinity Capture-MS), TIMM17A (Affinity Capture-MS), ELOVL5 (Affinity Capture-MS), ROMO1 (Affinity Capture-MS), TIMM17A (Affinity Capture-RNA), TIMM17A (Affinity Capture-MS), TIMM17A (Affinity Capture-MS), TIMM17A (Affinity Capture-MS), TIMM17A (Affinity Capture-MS), TIMM17A (Affinity Capture-MS), TIMM17A (Affinity Capture-MS), TIMM17A (Affinity Capture-MS), TIMM17A (Affinity Capture-MS)

ESM2 similar proteins: A4IFL0, B2RZ37, F1MDB2, F1N5S9, O14925, O35092, O35093, O49636, O60830, O95563, P11024, P38718, P39515, P59670, Q00765, Q0VCK9, Q13423, Q29RM3, Q2HJE9, Q5BIN4, Q5BJS4, Q5M7K0, Q5R4Z3, Q5RDD0, Q5RE33, Q5SRD1, Q5U4U5, Q5XH94, Q5XIA8, Q60870, Q6GM44, Q6INU6, Q8IVP5, Q8L7H8, Q8N5G0, Q91VC9, Q91ZQ0, Q99595, Q9CQ85, Q9D023

Diamond homologs: O35092, O44477, O60830, P39515, P59670, P87130, Q2HJE9, Q2UAP8, Q54K35, Q5BIN4, Q6BZY4, Q6NKU9, Q94EH2, Q99595, Q9C1E8, Q9CQ85, Q9JKW1, Q9LN27, Q9LYG1, Q9SP35, Q9VGA2, Q9VN97, Q9VNA0, Q9Z0V7, Q9Z0V8, A0A1D8PI78, P0CR88, P0CR89, P87146, Q5M7K0, Q9NAQ9, Q6FT37, A1XJK0, A2RVP7, O48528, Q12328, Q54QM0, Q5U4U5, Q6BT35, Q6CRJ6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TIMM17A	“form complex”	“TIM23 complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1012 predictions. Top by Δscore:

Variant	Effect	Δscore
1:201957272:T:A	acceptor_gain	1.0000
1:201957279:A:AG	acceptor_gain	1.0000
1:201957280:G:GG	acceptor_gain	1.0000
1:201957280:GC:G	acceptor_gain	1.0000
1:201957280:GCC:G	acceptor_gain	1.0000
1:201957280:GCCC:G	acceptor_gain	1.0000
1:201957378:GTG:G	donor_gain	1.0000
1:201957381:G:GG	donor_gain	1.0000
1:201957503:T:A	acceptor_gain	1.0000
1:201957507:ATAG:A	acceptor_gain	1.0000
1:201957507:ATAGG:A	acceptor_gain	1.0000
1:201957508:T:G	acceptor_gain	1.0000
1:201957508:TAGGG:T	acceptor_gain	1.0000
1:201957509:A:AG	acceptor_gain	1.0000
1:201957509:AG:A	acceptor_gain	1.0000
1:201957509:AGG:A	acceptor_gain	1.0000
1:201957509:AGGGA:A	acceptor_gain	1.0000
1:201957510:G:GT	acceptor_gain	1.0000
1:201957510:GG:G	acceptor_gain	1.0000
1:201957510:GGG:G	acceptor_gain	1.0000
1:201957510:GGGA:G	acceptor_gain	1.0000
1:201957510:GGGAG:G	acceptor_gain	1.0000
1:201957571:GGAG:G	donor_gain	1.0000
1:201957572:G:GT	donor_gain	1.0000
1:201957572:GAG:G	donor_gain	1.0000
1:201957573:AGG:A	donor_loss	1.0000
1:201957574:GGTA:G	donor_loss	1.0000
1:201957575:G:GA	donor_loss	1.0000
1:201957575:G:GG	donor_gain	1.0000
1:201957576:T:A	donor_loss	1.0000

AlphaMissense

1091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:201957300:G:C	D16H	1.000
1:201957301:A:T	D16V	1.000
1:201957307:G:A	G18D	1.000
1:201957324:G:C	G24R	1.000
1:201957324:G:T	G24C	1.000
1:201957325:G:A	G24D	1.000
1:201957334:G:A	G27D	1.000
1:201957337:G:A	G28D	1.000
1:201957572:G:A	G63E	1.000
1:201963621:T:C	F66L	1.000
1:201963622:T:C	F66S	1.000
1:201963623:T:A	F66L	1.000
1:201963623:T:G	F66L	1.000
1:201963625:C:A	A67E	1.000
1:201963630:T:A	W69R	1.000
1:201963630:T:C	W69R	1.000
1:201963632:G:C	W69C	1.000
1:201963632:G:T	W69C	1.000
1:201963633:G:A	G70R	1.000
1:201963633:G:C	G70R	1.000
1:201963634:G:A	G70E	1.000
1:201963637:G:A	G71E	1.000
1:201963642:T:A	F73I	1.000
1:201963642:T:C	F73L	1.000
1:201963643:T:C	F73S	1.000
1:201963644:T:A	F73L	1.000
1:201963644:T:G	F73L	1.000
1:201963698:C:A	N91K	1.000
1:201963698:C:G	N91K	1.000
1:201963703:T:A	I93N	1.000

dbSNP variants (sampled 300 via entrez): RS1000131923 (1:201953550 G>A,C), RS1000185883 (1:201960545 G>T), RS1000295142 (1:201966719 G>A), RS1000328603 (1:201964969 T>A), RS1000398304 (1:201964816 T>A,C), RS1000410873 (1:201966991 T>G), RS1000474564 (1:201953835 CCTTT>C), RS1000700812 (1:201955323 G>A), RS1000704869 (1:201960823 A>C), RS1000892267 (1:201960532 A>T), RS1001601470 (1:201963504 T>C), RS1001772832 (1:201958252 C>T), RS1002031034 (1:201960176 A>T), RS1002040538 (1:201966662 G>A,C), RS1002098597 (1:201954696 G>A)

Disease associations

OMIM: gene MIM:605057 | 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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	increases abundance, decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
arsenite	decreases expression, increases degradation, increases expression, affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
1,10-phenanthroline	decreases reaction, decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
tamibarotene	affects expression	1
2-palmitoylglycerol	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Adenosine Triphosphate	decreases expression, decreases reaction	1
Amiodarone	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases 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_B3J8	Abcam HEK293T TIMM17A KO	Transformed cell line	Female

Clinical trials (associated diseases)

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