TIMM10B

Summary

TIMM10B (translocase of inner mitochondrial membrane 10B, HGNC:4022) is a protein-coding gene on chromosome 11p15.4, encoding Mitochondrial import inner membrane translocase subunit Tim10 B (Q9Y5J6). Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane.

FXC1, or TIMM10B, belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.

Source: NCBI Gene 26515 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_012192

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4022
Approved symbol	TIMM10B
Name	translocase of inner mitochondrial membrane 10B
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	Tim9b, TIM10B
Ensembl gene	ENSG00000132286
Ensembl biotype	protein_coding
OMIM	607388
Entrez	26515

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000254616, ENST00000528908, ENST00000530751, ENST00000531462, ENST00000533379, ENST00000853132, ENST00000853133

RefSeq mRNA: 1 — MANE Select: NM_012192 NM_012192

CCDS: CCDS7766

Canonical transcript exons

ENST00000254616 — 3 exons

Exon	Start	End
ENSE00000988631	6482045	6484681
ENSE00003482762	6481501	6481555
ENSE00003581882	6481757	6481852

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 92.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.6330 / max 263.5127, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112857	31.6156	1822
112858	1.0174	630

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.15	gold quality
adrenal tissue	UBERON:0018303	91.62	gold quality
tibia	UBERON:0000979	90.57	gold quality
sperm	CL:0000019	90.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.23	gold quality
saphenous vein	UBERON:0007318	90.03	gold quality
colonic epithelium	UBERON:0000397	89.76	gold quality
superior vestibular nucleus	UBERON:0007227	89.72	gold quality
dorsal root ganglion	UBERON:0000044	89.62	gold quality
oocyte	CL:0000023	89.25	gold quality
esophagus squamous epithelium	UBERON:0006920	89.02	gold quality
ventral tegmental area	UBERON:0002691	88.87	gold quality
amniotic fluid	UBERON:0000173	88.86	gold quality
trigeminal ganglion	UBERON:0001675	88.79	gold quality
adrenal gland	UBERON:0002369	88.76	gold quality
renal medulla	UBERON:0000362	88.74	gold quality
tendon of biceps brachii	UBERON:0008188	88.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.62	gold quality
right adrenal gland cortex	UBERON:0035827	88.49	gold quality
stromal cell of endometrium	CL:0002255	88.43	gold quality
left adrenal gland	UBERON:0001234	88.43	gold quality
adrenal cortex	UBERON:0001235	88.37	gold quality
popliteal artery	UBERON:0002250	88.36	gold quality
tibial artery	UBERON:0007610	88.35	gold quality
islet of Langerhans	UBERON:0000006	88.31	gold quality
right adrenal gland	UBERON:0001233	88.25	gold quality
left adrenal gland cortex	UBERON:0035825	88.08	gold quality
aorta	UBERON:0000947	88.03	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.97	gold quality
prefrontal cortex	UBERON:0000451	87.96	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	282.54
E-MTAB-7303	no	161.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

102 targeting TIMM10B, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3941	99.86	70.54	2735

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	timm10b	ENSDARG00000043898
mus_musculus	Timm10b	ENSMUSG00000089847
rattus_norvegicus	Timm10b	ENSRNOG00000050846
drosophila_melanogaster	Tim9b	FBGN0027358

Protein

Protein identifiers

Mitochondrial import inner membrane translocase subunit Tim10 B — Q9Y5J6 (reviewed: Q9Y5J6)

Alternative names: Fracture callus protein 1, FxC1, Mitochondrial import inner membrane translocase subunit Tim9 B, TIMM10B

All UniProt accessions (3): Q9Y5J6, B2R4A9, F2Z2B0

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. In the TIM22 complex, it may act as a docking point for the soluble 70 kDa complex that guides the target proteins in transit through the aqueous mitochondrial intermembrane space.

Subunit / interactions. Component of the TIM22 complex, which core is composed of TIMM22, associated with TIMM10 (TIMM10A and/or TIMM10B), TIMM9, AGK and TIMM29.

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 TIMM10B 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_036324* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004217	Tim10-like	Domain
IPR035427	Tim10-like_dom_sf	Homologous_superfamily
IPR050673	Mito_inner_translocase_sub	Family

Pfam: PF02953

UniProt features (6 total): disulfide bond 2, sequence variant 2, chain 1, short sequence motif 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-Q9Y5J6-F1	90.13	0.85

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 (2): 28–52, 32–48

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 144 (showing top): AREB6_03, MAZ_Q6, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GGGTGGRR_PAX4_03, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, HEN1_01, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, TGGNNNNNNKCCAR_UNKNOWN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_CELL_SUBSTRATE_ADHESION, GOBP_CELL_MATRIX_ADHESION

GO Biological Process (3): cell-matrix adhesion (GO:0007160), protein transport (GO:0015031), protein insertion into mitochondrial inner membrane (GO:0045039)

GO Molecular Function (4): metal ion binding (GO:0046872), obsolete unfolded protein binding (GO:0051082), protein transporter activity (GO:0140318), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial intermembrane space chaperone complex (GO:0042719), TIM22 mitochondrial import inner membrane insertion complex (GO:0042721), 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
cell-substrate adhesion	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
inner mitochondrial membrane organization	1
mitochondrial protein import pathway	1
cation binding	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
mitochondrial intermembrane space	1
mitochondrial protein-containing complex	1
inner mitochondrial membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIMM10B	TIMM8A	O60220	935
TIMM10B	TIMM29	Q9BSF4	908
TIMM10B	TIMM10	P62072	889
TIMM10B	TIMM9	Q9Y5J7	820
TIMM10B	AGK	Q53H12	781
TIMM10B	CHCHD4	Q8N4Q1	711
TIMM10B	TIMM22	Q9Y584	706
TIMM10B	TIMM8B	Q9Y5J9	690
TIMM10B	TIMM50	Q3ZCQ8	665
TIMM10B	TIMM13	P62206	643
TIMM10B	TIMM17A	Q99595	642
TIMM10B	TIMM21	Q9BVV7	625
TIMM10B	TIMM17B	O60830	607
TIMM10B	TIMM44	O43615	574
TIMM10B	TOMM22	Q9NS69	543
TIMM10B	AGFG2	O95081	543

IntAct

50 interactions, top by confidence:

A	B	Type	Score
TIMM9	TIMM10	psi-mi:“MI:0914”(association)	0.830
CNOT11	CNOT1	psi-mi:“MI:0914”(association)	0.770
TIMM10B	TIMM10	psi-mi:“MI:0914”(association)	0.710
TIMM10	TIMM10B	psi-mi:“MI:0914”(association)	0.710
TIMM10B	TIMM10	psi-mi:“MI:0915”(physical association)	0.710
TIMM10	AGK	psi-mi:“MI:0914”(association)	0.640
AGK	HCCS	psi-mi:“MI:0914”(association)	0.620
HGS	TIMM10B	psi-mi:“MI:0915”(physical association)	0.560
MEIS2	TIMM10B	psi-mi:“MI:0915”(physical association)	0.560
MBD3	TIMM10B	psi-mi:“MI:0915”(physical association)	0.560
EIF3F	TIMM10B	psi-mi:“MI:0915”(physical association)	0.560
KLHL38	TIMM10B	psi-mi:“MI:0915”(physical association)	0.560
rep	IDE	psi-mi:“MI:0914”(association)	0.530
PNOC	CETN3	psi-mi:“MI:0914”(association)	0.530
ADCYAP1	GGPS1	psi-mi:“MI:0914”(association)	0.530
MSI2	TIMM10B	psi-mi:“MI:0915”(physical association)	0.500
TIMM22	TIMM10	psi-mi:“MI:0914”(association)	0.350
ADCYAP1	CETN3	psi-mi:“MI:0914”(association)	0.350
MSI2	ANXA13	psi-mi:“MI:0914”(association)	0.350
AGK	ATP12A	psi-mi:“MI:0914”(association)	0.350
PRDM1	HSPD1	psi-mi:“MI:0914”(association)	0.350
MRPL51		psi-mi:“MI:0914”(association)	0.350
TIMM10	DCTN6	psi-mi:“MI:0914”(association)	0.350
TTLL4	ANKRD28	psi-mi:“MI:0914”(association)	0.350
HPSE2	RNF13	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): TIMM10B (Affinity Capture-MS), TIMM10B (Affinity Capture-MS), TIMM10B (Affinity Capture-MS), TIMM10B (Affinity Capture-MS), TIMM10B (Affinity Capture-MS), TIMM10B (Affinity Capture-MS), TIMM10B (Affinity Capture-MS), TIMM10B (Two-hybrid), MEIS2 (Two-hybrid), EIF3F (Two-hybrid), KLHL38 (Two-hybrid), HGS (Two-hybrid), TIMM10B (Two-hybrid), TIMM10B (Two-hybrid), TIMM10B (Two-hybrid)

ESM2 similar proteins: A1L188, A2AMZ4, A2XK00, A7YY73, B4FGS2, B4FTR7, B8B624, C0HAV3, C5E268, G2TRP6, O13973, O75012, O95159, O95872, Q0VDN7, Q12894, Q28H71, Q2YDD3, Q3SZA2, Q3SZW4, Q3U0S6, Q3UJV1, Q49AH0, Q4G012, Q5FVV3, Q5U509, Q5U651, Q61858, Q6ASS9, Q6P0I6, Q756Q5, Q7S4Y4, Q7XAM0, Q7XK12, Q8BGD8, Q8BGX2, Q8CC36, Q8VED2, Q96BP2, Q96C34

Diamond homologs: O60220, P0CR94, P0CR95, P57744, P62077, P62078, Q09783, Q3SZ93, Q3SZW4, Q3ZBS8, Q4FZG7, Q4IJW4, Q59MI8, Q5RDJ0, Q66L32, Q6BHJ3, Q6BN23, Q6CIK7, Q6CWH5, Q6DEM5, Q6FK81, Q6GR66, Q759W7, Q75DU7, Q90YI5, Q9P335, Q9R1B1, Q9VTN3, Q9WV96, Q9WVA1, Q9WVA2, Q9XGY4, Q9Y1A3, Q9Y5J6, Q9Y5J9, Q9Y8C0, O74700, P0CR96, P0CR97, P57745

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
Mitochondrial protein import	5	25.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

217 predictions. Top by Δscore:

Variant	Effect	Δscore
11:6481551:GAAAC:G	donor_gain	1.0000
11:6481552:AAAC:A	donor_gain	1.0000
11:6481553:AAC:A	donor_gain	1.0000
11:6481553:AACG:A	donor_loss	1.0000
11:6481554:AC:A	donor_gain	1.0000
11:6481555:CGTA:C	donor_loss	1.0000
11:6481556:G:C	donor_loss	1.0000
11:6481556:G:GG	donor_gain	1.0000
11:6481560:G:GG	donor_gain	1.0000
11:6481756:GCTGC:G	acceptor_gain	1.0000
11:6481850:G:GT	donor_gain	1.0000
11:6481557:T:A	donor_loss	0.9900
11:6481754:CAGCT:C	acceptor_loss	0.9900
11:6481755:A:AC	acceptor_loss	0.9900
11:6481755:A:AG	acceptor_gain	0.9900
11:6481756:G:GG	acceptor_gain	0.9900
11:6481756:GCT:G	acceptor_gain	0.9900
11:6481841:G:GT	donor_gain	0.9900
11:6481870:G:T	donor_gain	0.9900
11:6482039:TTCTA:T	acceptor_loss	0.9900
11:6482040:TCTA:T	acceptor_loss	0.9900
11:6482042:TA:T	acceptor_loss	0.9900
11:6482043:A:T	acceptor_loss	0.9900
11:6481845:C:G	donor_gain	0.9800
11:6481849:GGAG:G	donor_gain	0.9800
11:6481851:AGGTG:A	donor_loss	0.9800
11:6481852:GG:G	donor_loss	0.9800
11:6481853:GT:G	donor_loss	0.9800
11:6481854:T:G	donor_loss	0.9800
11:6482043:A:AG	acceptor_gain	0.9800

AlphaMissense

662 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:6481766:T:C	F17L	0.999
11:6481768:C:A	F17L	0.999
11:6481768:C:G	F17L	0.999
11:6481802:T:C	F29L	0.998
11:6481804:C:A	F29L	0.998
11:6481804:C:G	F29L	0.998
11:6482064:G:A	C52Y	0.998
11:6481767:T:G	F17C	0.997
11:6481799:T:C	C28R	0.997
11:6481800:G:A	C28Y	0.997
11:6482067:C:A	A53D	0.997
11:6481770:T:C	L18P	0.996
11:6481783:T:A	N22K	0.996
11:6481783:T:G	N22K	0.996
11:6481791:C:T	T25I	0.996
11:6481801:C:G	C28W	0.996
11:6482063:T:C	C52R	0.996
11:6482108:T:G	Y67D	0.996
11:6481767:T:C	F17S	0.995
11:6481778:T:G	Y21D	0.995
11:6481803:T:C	F29S	0.995
11:6481803:T:G	F29C	0.995
11:6481811:T:C	C32R	0.995
11:6482063:T:A	C52S	0.995
11:6482064:G:C	C52S	0.995
11:6482065:T:G	C52W	0.995
11:6482089:C:A	N60K	0.995
11:6482089:C:G	N60K	0.995
11:6482051:T:C	C48R	0.994
11:6482052:G:A	C48Y	0.994

dbSNP variants (sampled 300 via entrez): RS1000365664 (11:6481926 C>G), RS1000681000 (11:6484558 G>C), RS1001483841 (11:6482248 C>G,T), RS1002050326 (11:6482457 A>G), RS1002259766 (11:6484191 C>A), RS1002483645 (11:6483555 C>T), RS1002604500 (11:6483841 C>T), RS1003530884 (11:6482985 T>A), RS1003717335 (11:6479545 G>A), RS1003881127 (11:6481637 G>A,T), RS1005048709 (11:6480479 C>A,G,T), RS1005287628 (11:6482773 A>G,T), RS1005427248 (11:6482942 A>T), RS1005436155 (11:6482490 A>G), RS1006399067 (11:6483913 T>C)

Disease associations

OMIM: gene MIM:607388 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002058_3	DNA methylation (variation)	5.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0022599	DNA methylation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Leflunomide	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenite	increases expression	1
nickel chloride	decreases expression	1
cupric oxide	increases expression	1
resorcinol	increases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Lead	decreases expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Copper Sulfate	decreases expression	1
Genistein	decreases expression, increases reaction	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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