TIMM29

Summary

TIMM29 (translocase of inner mitochondrial membrane 29, HGNC:25152) is a protein-coding gene on chromosome 19p13.2, encoding Mitochondrial import inner membrane translocase subunit Tim29 (Q9BSF4). Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. It is a selective cancer dependency (DepMap: 62.7% of cell lines).

Enables protein transporter activity. Involved in protein insertion into mitochondrial inner membrane. Located in mitochondrial inner membrane and mitochondrial intermembrane space. Part of TIM22 mitochondrial import inner membrane insertion complex.

Source: NCBI Gene 90580 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 6 total
• Cancer dependency (DepMap): dependent in 62.7% of screened cell lines
• MANE Select transcript: NM_138358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25152
Approved symbol	TIMM29
Name	translocase of inner mitochondrial membrane 29
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	TIM29
Ensembl gene	ENSG00000142444
Ensembl biotype	protein_coding
OMIM	617380
Entrez	90580

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000270502, ENST00000588807, ENST00000593162

RefSeq mRNA: 1 — MANE Select: NM_138358 NM_138358

CCDS: CCDS12252

Canonical transcript exons

ENST00000270502 — 2 exons

Exon	Start	End
ENSE00000954157	10928811	10928916
ENSE00000954158	10929014	10930254

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 89.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.7086 / max 52.7325, expressed in 1767 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173876	7.0850	1749
173875	1.0576	661
173874	0.5660	314

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	89.16	gold quality
leukocyte	CL:0000738	88.98	gold quality
gastrocnemius	UBERON:0001388	88.38	gold quality
lower esophagus mucosa	UBERON:0035834	88.31	gold quality
muscle of leg	UBERON:0001383	87.91	gold quality
mucosa of transverse colon	UBERON:0004991	87.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.65	gold quality
stromal cell of endometrium	CL:0002255	87.48	gold quality
cerebellar hemisphere	UBERON:0002245	86.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.79	gold quality
cerebellar cortex	UBERON:0002129	86.70	gold quality
right adrenal gland cortex	UBERON:0035827	86.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.17	gold quality
apex of heart	UBERON:0002098	86.10	gold quality
right adrenal gland	UBERON:0001233	86.06	gold quality
skin of leg	UBERON:0001511	86.04	gold quality
left adrenal gland	UBERON:0001234	85.84	gold quality
right lobe of liver	UBERON:0001114	85.83	gold quality
left adrenal gland cortex	UBERON:0035825	85.66	gold quality
skin of abdomen	UBERON:0001416	85.60	gold quality
granulocyte	CL:0000094	85.38	gold quality
anterior cingulate cortex	UBERON:0009835	85.38	gold quality
adenohypophysis	UBERON:0002196	85.28	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.17	gold quality
right frontal lobe	UBERON:0002810	85.15	gold quality
body of stomach	UBERON:0001161	85.05	gold quality
lower esophagus	UBERON:0013473	85.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.02	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.90	gold quality
esophagus mucosa	UBERON:0002469	84.86	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting TIMM29, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-668-3P	96.18	65.80	673
HSA-MIR-3677-5P	93.16	64.62	393
HSA-MIR-4747-3P	87.34	61.83	60

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 62.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Here, the authors identify Tim29 (C19orf52) as a novel, metazoan-specific subunit of the human TIM22 complex. The protein is integrated into the mitochondrial inner membrane with it’s C-terminus exposed to the intermembrane space. (PMID:27554484)
• TIM29 is required for the structural integrity of the TIM22 complex and for import of substrate proteins by the carrier translocase (PMID:27718247)
• TIMM29 interacts with hepatitis B virus preS1 to modulate the HBV life cycle. (PMID:32970362)
• Defining the architecture of the human TIM22 complex by chemical crosslinking. (PMID:33125709)
• TIM22 and TIM29 inhibit HBV replication by up-regulating SRSF1 expression. (PMID:38294104)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	timm29	ENSDARG00000037909
mus_musculus	Timm29	ENSMUSG00000048429
rattus_norvegicus	Timm29	ENSRNOG00000083564
drosophila_melanogaster	CG14270	FBGN0029665
caenorhabditis_elegans		WBGENE00011017

Protein

Protein identifiers

Mitochondrial import inner membrane translocase subunit Tim29 — Q9BSF4 (reviewed: Q9BSF4)

All UniProt accessions (2): Q9BSF4, K7ENF5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translocase that uses the membrane potential as the external driving force. Required for the stability of the TIM22 complex and functions in the assembly of the TIMM22 protein into the TIM22 complex. May facilitate cooperation between TIM22 and TOM complexes by interacting with TOMM40.

Subunit / interactions. Component of the TIM22 complex, which core is composed of TIMM22, associated with TIMM10 (TIMM10A and/or TIMM10B), TIMM9, AGK and TIMM29. Interacts with TIMM10B; the interaction is direct. Interacts with TOMM40; linking the TIM22 complex to the TOM complex. Interacts with TIMM22 (when oxidized); the interaction is direct.

Subcellular location. Mitochondrion inner membrane.

RefSeq proteins (1): NP_612367* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019322	TIMM29	Family

Pfam: PF10171

UniProt features (5 total): topological domain 2, transit peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7CGP	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSF4-F1	87.30	0.61

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 89 (showing top): GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, ACEVEDO_LIVER_CANCER_UP, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_INNER_MITOCHONDRIAL_MEMBRANE_PROTEIN_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (2): protein transport (GO:0015031), protein insertion into mitochondrial inner membrane (GO:0045039)

GO Molecular Function (2): protein transporter activity (GO:0140318), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), TIM22 mitochondrial import inner membrane insertion complex (GO:0042721), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
intracellular protein localization	1
establishment of protein localization	1
inner mitochondrial membrane organization	1
mitochondrial protein import pathway	1
transporter activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
inner mitochondrial membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIMM29	TIMM10B	Q9Y5J6	908
TIMM29	TIMM22	Q9Y584	835
TIMM29	AGK	Q53H12	801
TIMM29	TIMM9	Q9Y5J7	783
TIMM29	TIMM10	P62072	765
TIMM29	TIMM23	O14925	604
TIMM29	TIMM17A	Q99595	602
TIMM29	TIMM21	Q9BVV7	520
TIMM29	TOMM5	Q8N4H5	472
TIMM29	DESI2	Q9BSY9	458
TIMM29	TIMM50	Q3ZCQ8	447
TIMM29	TOMM7	Q9P0U1	438
TIMM29	TOMM22	Q9NS69	432
TIMM29	TIMM8A	O60220	420
TIMM29	TIMM44	O43615	418

IntAct

87 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
EIF3F	EIF3CL	psi-mi:“MI:0914”(association)	0.640
TOMM22	XRCC3	psi-mi:“MI:0914”(association)	0.640
TIMM10	AGK	psi-mi:“MI:0914”(association)	0.640
ALOX15	TIMM29	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TOR1AIP2	TMEM223	psi-mi:“MI:0914”(association)	0.530
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
ITGB8	GET1	psi-mi:“MI:0914”(association)	0.530
FAM131B	AURKA	psi-mi:“MI:0914”(association)	0.530
rep	IDE	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530
MGRN1	ATRN	psi-mi:“MI:0914”(association)	0.530
ANKS6	DCAF7	psi-mi:“MI:0914”(association)	0.510
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
CEP43	CCHCR1	psi-mi:“MI:0914”(association)	0.350
CDK1	CHEK1	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
AP1S2	SLC43A3	psi-mi:“MI:0914”(association)	0.350
NCSTN	ESYT2	psi-mi:“MI:0914”(association)	0.350
AP4M1		psi-mi:“MI:0914”(association)	0.350
AP4S1	RPL10	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
ERGIC3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA9	TMEM120B	psi-mi:“MI:0914”(association)	0.350

BioGRID (162): C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS), C19orf52 (Affinity Capture-MS)

ESM2 similar proteins: A1A4P4, A1CH36, A2ALW5, A5AAL8, B0BN56, O42911, O70279, P0C2B7, P58468, P83565, Q0CLE8, Q1ECT8, Q290P4, Q2GVC2, Q3SZ86, Q4G0I0, Q4V7Q1, Q5B4U6, Q5BJW9, Q5RFR4, Q5XJW2, Q61733, Q6RUT7, Q753F1, Q7SDU5, Q7SHR9, Q80ZS3, Q86TS9, Q8BGX2, Q8BK72, Q8CHP5, Q8SPE7, Q8TAE8, Q8VD26, Q8WUQ7, Q96AN5, Q96DF8, Q9BRP8, Q9BSF4, Q9BYN8

Diamond homologs: Q8BGX2, Q9BSF4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TIMM29	“form complex”	“TIM22 complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

82 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10928898:G:GT	donor_gain	1.0000
19:10928884:T:TA	donor_gain	0.9900
19:10928885:A:AA	donor_gain	0.9900
19:10928912:GCTGG:G	donor_gain	0.9900
19:10928915:GG:G	donor_gain	0.9900
19:10928916:GG:G	donor_gain	0.9900
19:10928917:G:C	donor_loss	0.9900
19:10928917:G:GG	donor_gain	0.9900
19:10928918:TGA:T	donor_loss	0.9900
19:10928919:GAG:G	donor_loss	0.9900
19:10928920:AGTAG:A	donor_loss	0.9900
19:10929008:CCTCA:C	acceptor_loss	0.9800
19:10929009:CTCAG:C	acceptor_loss	0.9800
19:10929010:TCAGG:T	acceptor_loss	0.9800
19:10929011:CAGGG:C	acceptor_loss	0.9800
19:10929012:AG:A	acceptor_gain	0.9800
19:10929013:G:T	acceptor_loss	0.9800
19:10929013:GG:G	acceptor_gain	0.9800
19:10929012:A:AG	acceptor_gain	0.9700
19:10929013:G:GG	acceptor_gain	0.9700
19:10928914:TGG:T	donor_gain	0.9500
19:10928915:GGG:G	donor_gain	0.9500
19:10928886:G:GG	donor_gain	0.9400
19:10929013:GGGT:G	acceptor_gain	0.9400
19:10929012:AGG:A	acceptor_gain	0.9300
19:10929013:GGG:G	acceptor_gain	0.9300
19:10928898:G:T	donor_gain	0.9200
19:10928913:CTGG:C	donor_gain	0.9200
19:10929013:GGGTC:G	acceptor_gain	0.9100
19:10928918:T:G	donor_gain	0.7700

AlphaMissense

1645 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10929484:T:C	F189L	0.989
19:10929486:C:A	F189L	0.989
19:10929486:C:G	F189L	0.989
19:10929433:T:A	W172R	0.973
19:10929433:T:C	W172R	0.973
19:10929556:T:C	F213L	0.967
19:10929558:C:A	F213L	0.967
19:10929558:C:G	F213L	0.967
19:10929485:T:C	F189S	0.963
19:10929435:G:C	W172C	0.959
19:10929435:G:T	W172C	0.959
19:10929412:G:C	D165H	0.956
19:10929419:G:A	G167D	0.954
19:10929485:T:G	F189C	0.954
19:10929112:G:C	G65R	0.948
19:10929125:G:A	G69D	0.947
19:10929407:T:A	V163D	0.946
19:10929467:A:T	D183V	0.945
19:10929122:G:A	G68D	0.944
19:10929166:T:C	F83L	0.944
19:10929168:C:A	F83L	0.944
19:10929168:C:G	F83L	0.944
19:10929307:T:C	C130R	0.944
19:10929418:G:C	G167R	0.944
19:10929413:A:T	D165V	0.943
19:10929124:G:C	G69R	0.942
19:10929121:G:C	G68R	0.939
19:10929615:G:C	W232C	0.936
19:10929615:G:T	W232C	0.936
19:10929412:G:T	D165Y	0.935

dbSNP variants (sampled 300 via entrez): RS1000293261 (19:10930246 T>C,G), RS1000622819 (19:10928856 C>G,T), RS1000717211 (19:10928703 CT>C), RS1000793182 (19:10927346 A>G,T), RS1000855799 (19:10928782 G>A,C), RS1001512991 (19:10929892 G>A), RS1001773810 (19:10930025 C>G), RS1001949803 (19:10928469 TC>T,TCC), RS1002254766 (19:10928633 C>G), RS1004211671 (19:10928713 G>T), RS1004454312 (19:10928202 C>A,T), RS1004651806 (19:10927095 A>C), RS1004707851 (19:10928499 C>T), RS1005301767 (19:10929504 T>C), RS1006356165 (19:10930490 T>G)

Disease associations

OMIM: gene MIM:617380 | 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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, affects cotreatment	3
aristolochic acid I	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Ivermectin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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