MTX3

Summary

MTX3 (metaxin 3, HGNC:24812) is a protein-coding gene on chromosome 5q14.1, encoding Metaxin-3 (Q5HYI7). Could function in transport of proteins into the mitochondrion.

Predicted to be involved in mitochondrion organization. Located in mitochondrion. Part of MIB complex and SAM complex.

Source: NCBI Gene 345778 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_001363818

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24812
Approved symbol	MTX3
Name	metaxin 3
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000177034
Ensembl biotype	protein_coding
OMIM	619336
Entrez	345778

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000509852, ENST00000512528, ENST00000512560

RefSeq mRNA: 3 — MANE Select: NM_001363818 NM_001010891, NM_001167741, NM_001363818

CCDS: CCDS47239, CCDS54872, CCDS87308

Canonical transcript exons

ENST00000512528 — 9 exons

Exon	Start	End
ENSE00001306298	79989152	79989244
ENSE00001484424	79990594	79990663
ENSE00001691033	79988462	79988644
ENSE00001718814	79986950	79987107
ENSE00001758905	79985571	79985659
ENSE00001767460	79988239	79988315
ENSE00002026778	79976716	79983794
ENSE00003466619	79990160	79990236
ENSE00003899559	79991158	79991262

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 92.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1998 / max 146.3959, expressed in 1643 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62282	8.4280	1611
62280	1.2526	646
62281	0.2778	128
62278	0.2414	92

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	92.05	gold quality
deltoid	UBERON:0001476	91.02	gold quality
tibialis anterior	UBERON:0001385	90.93	gold quality
upper arm skin	UBERON:0004263	88.81	gold quality
calcaneal tendon	UBERON:0003701	87.92	gold quality
substantia nigra pars compacta	UBERON:0001965	87.90	gold quality
pancreatic ductal cell	CL:0002079	87.87	silver quality
parotid gland	UBERON:0001831	87.65	gold quality
pons	UBERON:0000988	87.63	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.99	gold quality
ileal mucosa	UBERON:0000331	86.92	gold quality
epithelium of nasopharynx	UBERON:0001951	86.79	gold quality
endothelial cell	CL:0000115	86.50	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.04	gold quality
epithelial cell of pancreas	CL:0000083	85.59	gold quality
tendon	UBERON:0000043	85.04	gold quality
lateral globus pallidus	UBERON:0002476	84.84	gold quality
layer of synovial tissue	UBERON:0007616	84.70	gold quality
superior vestibular nucleus	UBERON:0007227	84.60	gold quality
adrenal tissue	UBERON:0018303	84.53	gold quality
left ventricle myocardium	UBERON:0006566	84.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.01	gold quality
corpus epididymis	UBERON:0004359	83.84	gold quality
superficial temporal artery	UBERON:0001614	83.82	gold quality
skin of hip	UBERON:0001554	83.63	gold quality
palpebral conjunctiva	UBERON:0001812	83.55	gold quality
caput epididymis	UBERON:0004358	83.43	gold quality
medulla oblongata	UBERON:0001896	83.20	gold quality
trigeminal ganglion	UBERON:0001675	83.17	gold quality
endometrium	UBERON:0001295	83.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

325 targeting MTX3, 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-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtx3	ENSDARG00000090195
mus_musculus	Mtx3	ENSMUSG00000021704
rattus_norvegicus	Mtx3	ENSRNOG00000075938
drosophila_melanogaster	CG9393	FBGN0037710
caenorhabditis_elegans	mtx-1	WBGENE00009559

Paralogs (3): MTX2 (ENSG00000128654), FAXC (ENSG00000146267), MTX1 (ENSG00000173171)

Protein

Protein identifiers

Metaxin-3 — Q5HYI7 (reviewed: Q5HYI7)

All UniProt accessions (1): Q5HYI7

UniProt curated annotations — full annotation on UniProt →

Function. Could function in transport of proteins into the mitochondrion.

Subunit / interactions. Part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.

Subcellular location. Mitochondrion. Mitochondrion outer membrane.

Similarity. Belongs to the metaxin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5HYI7-1	1	yes
Q5HYI7-2	2
Q5HYI7-4	3
Q5HYI7-5	4

RefSeq proteins (3): NP_001010891, NP_001161213, NP_001350747* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017410	Metaxin1/3	Family
IPR019564	Sam37/metaxin_N	Domain
IPR033468	Metaxin_GST	Domain
IPR036282	Glutathione-S-Trfase_C_sf	Homologous_superfamily
IPR040079	Glutathione_S-Trfase	Family
IPR050931	Mito_Protein_Transport_Metaxin	Family

Pfam: PF10568, PF17171

UniProt features (12 total): splice variant 5, modified residue 3, chain 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5HYI7-F1	84.60	0.65

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): 249, 284, 311

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_INNER_MITOCHONDRIAL_MEMBRANE_ORGANIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, ACEVEDO_LIVER_CANCER_UP, AACTGGA_MIR145, GOBP_PROTEIN_INSERTION_INTO_MEMBRANE, GOCC_OUTER_MITOCHONDRIAL_MEMBRANE_PROTEIN_COMPLEX, AACATTC_MIR4093P, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (3): mitochondrion organization (GO:0007005), inner mitochondrial membrane organization (GO:0007007), protein transport (GO:0015031)

GO Molecular Function (0):

GO Cellular Component (5): SAM complex (GO:0001401), mitochondrion (GO:0005739), MIB complex (GO:0140275), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	1
mitochondrial membrane organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
mitochondrial outer membrane translocase complex	1
cytoplasm	1
intracellular membrane-bounded organelle	1
inner mitochondrial membrane protein complex	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTX3	SAMM50	Q9Y512	864
MTX3	MTX2	O75431	849
MTX3	TOMM22	Q9NS69	520
MTX3	DNAJC11	Q9NVH1	519
MTX3	CHCHD6	Q9BRQ6	513
MTX3	TOMM7	Q9P0U1	489
MTX3	AREL1	O15033	472
MTX3	MTX1	Q13505	464
MTX3	CHCHD3	Q9NX63	450
MTX3	OR4N5	Q8IXE1	450
MTX3	CMYA5	Q8N3K9	431
MTX3	TIMM21	Q9BVV7	418
MTX3	TOMM70	O94826	414
MTX3	TIMM10	P62072	395
MTX3	TIMM50	Q3ZCQ8	392

IntAct

70 interactions, top by confidence:

A	B	Type	Score
RPS14	MAGEB2	psi-mi:“MI:0914”(association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
CD68	TNPO2	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
CLEC5A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
APOOL	MTX2	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
CD244	MTX2	psi-mi:“MI:0914”(association)	0.530
Mtx2	NRDC	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
BSCL2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SV2A	ILVBL	psi-mi:“MI:0914”(association)	0.350
MLNR	NBAS	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
FAXC	METTL15	psi-mi:“MI:0914”(association)	0.350
PTH2R	METTL15	psi-mi:“MI:0914”(association)	0.350
CRLF2	METTL15	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MGARP	RTL8C	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350

BioGRID (115): MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), MTX3 (Affinity Capture-MS)

ESM2 similar proteins: A0JM23, A4IGD2, A5PKL6, A6NHR9, A6QQZ0, D3ZAT9, F1QWA8, O35099, O88741, O94952, P0CI65, P58005, Q29RL0, Q2TBQ7, Q3U213, Q3UMF9, Q4R6P7, Q4R6Y8, Q5E9N5, Q5F204, Q5HYI7, Q5I0G3, Q5IH14, Q5R5S1, Q5R9R1, Q5RL51, Q5TGI0, Q60649, Q6AZT7, Q6DDI6, Q6DDT5, Q6DEY8, Q6NXY1, Q6YXW6, Q7TNH6, Q7Z494, Q8NBP0, Q8NEC7, Q8TB36, Q94E75

Diamond homologs: A8XWD1, O45503, O75431, P47802, Q13505, Q27HK4, Q2TBS1, Q3KPT9, Q4R3I0, Q4VBW0, Q5HYI7, Q9VHB6, O64471, P34599

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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	10.8×	9e-03
Mitochondrial biogenesis	5	10.8×	9e-03
SLC-mediated transmembrane transport	9	6.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1051 predictions. Top by Δscore:

Variant	Effect	Δscore
5:79983790:TCCAT:T	acceptor_gain	1.0000
5:79983791:CCAT:C	acceptor_gain	1.0000
5:79983791:CCATC:C	acceptor_gain	1.0000
5:79983792:CAT:C	acceptor_gain	1.0000
5:79983792:CATC:C	acceptor_gain	1.0000
5:79983793:ATCT:A	acceptor_loss	1.0000
5:79983795:C:CC	acceptor_gain	1.0000
5:79983795:C:T	acceptor_loss	1.0000
5:79983796:T:A	acceptor_loss	1.0000
5:79985540:A:C	donor_gain	1.0000
5:79985590:T:TA	donor_gain	1.0000
5:79985681:C:CT	acceptor_gain	1.0000
5:79986944:GCTTA:G	donor_loss	1.0000
5:79986945:CTTAC:C	donor_loss	1.0000
5:79986946:TTACC:T	donor_loss	1.0000
5:79986947:TA:T	donor_loss	1.0000
5:79987067:G:C	acceptor_gain	1.0000
5:79987067:G:GC	acceptor_gain	1.0000
5:79987108:C:CC	acceptor_gain	1.0000
5:79988458:ATAC:A	donor_loss	1.0000
5:79988459:TA:T	donor_loss	1.0000
5:79988460:A:C	donor_loss	1.0000
5:79988461:CCTGT:C	donor_loss	1.0000
5:79988640:TGAAG:T	acceptor_gain	1.0000
5:79988641:GAAG:G	acceptor_gain	1.0000
5:79988643:AG:A	acceptor_gain	1.0000
5:79988645:C:CC	acceptor_gain	1.0000
5:79989144:ACACT:A	donor_loss	1.0000
5:79989145:CACTC:C	donor_loss	1.0000
5:79989146:ACTCA:A	donor_loss	1.0000

AlphaMissense

2028 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:79987078:C:T	G204D	0.997
5:79988303:C:G	A173P	0.996
5:79989192:G:T	A94D	0.996
5:79987090:G:T	A200D	0.995
5:79988290:A:G	L177P	0.995
5:79989165:A:G	L103P	0.995
5:79989180:A:G	L98P	0.995
5:79988632:A:G	W112R	0.993
5:79988632:A:T	W112R	0.993
5:79987079:C:G	G204R	0.992
5:79988284:A:G	L179P	0.992
5:79988294:A:G	C176R	0.992
5:79990663:C:G	A28P	0.992
5:79988302:G:T	A173D	0.991
5:79989184:C:G	A97P	0.991
5:79987021:A:G	L223P	0.990
5:79987084:A:T	V202D	0.990
5:79988279:A:G	S181P	0.990
5:79988281:A:G	L180P	0.990
5:79990656:G:T	A30D	0.990
5:79989222:A:G	L84P	0.989
5:79989232:C:G	D81H	0.989
5:79990182:A:T	I69K	0.989
5:79987091:C:G	A200P	0.988
5:79987094:C:G	D199H	0.988
5:79990650:A:G	F32S	0.988
5:79990657:C:G	A30P	0.988
5:79990662:G:T	A28D	0.988
5:79988292:G:C	C176W	0.987
5:79989156:G:T	A106E	0.987

dbSNP variants (sampled 300 via entrez): RS1000069361 (5:79986575 G>A), RS1000540580 (5:79979166 A>G), RS1000644949 (5:79979957 G>A), RS1000920327 (5:79991994 C>G,T), RS1001312955 (5:79977931 C>T), RS1001545346 (5:79981038 T>C), RS1001609404 (5:79991513 G>A,C,T), RS1001617410 (5:79981282 A>G), RS1001739225 (5:79985175 G>A,T), RS1001748924 (5:79985040 G>A), RS1001911499 (5:79987640 A>G), RS1001995762 (5:79990028 T>C), RS1002060364 (5:79991213 C>G,T), RS1002082658 (5:79983461 C>A,G,T), RS1002345062 (5:79990298 T>A)

Disease associations

OMIM: gene MIM:619336 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006364_2	Hepatitis B surface antigen seroclearance in chronic hepatitis B infection	4.000000e-06
GCST010002_31	Refractive error	1.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009345	Hepatitis B virus surface antigen seropositivity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
Leflunomide	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases abundance, increases expression	1
Folic Acid	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Thapsigargin	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_D9KS	Ubigene HEK293 MTX3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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