MIX23

Summary

MIX23 (mitochondrial matrix import factor 23, HGNC:31136) is a protein-coding gene on chromosome 3q21.1, encoding Protein MIX23 (Q4VC31). It is a selective cancer dependency (DepMap: 16.8% of cell lines).

Located in mitochondrion.

Source: NCBI Gene 131076 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 27 total
• Cancer dependency (DepMap): dependent in 16.8% of screened cell lines
• MANE Select transcript: NM_001017928

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31136
Approved symbol	MIX23
Name	mitochondrial matrix import factor 23
Location	3q21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33273
Ensembl gene	ENSG00000160124
Ensembl biotype	protein_coding
OMIM	620713
Entrez	131076

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000291458, ENST00000460810, ENST00000466854, ENST00000479414, ENST00000479899, ENST00000497726, ENST00000498466, ENST00000906685, ENST00000906686, ENST00000906687, ENST00000920727, ENST00000920728, ENST00000920729

RefSeq mRNA: 2 — MANE Select: NM_001017928 NM_001017928, NM_001308326

CCDS: CCDS33838, CCDS77802

Canonical transcript exons

ENST00000291458 — 5 exons

Exon	Start	End
ENSE00001049955	122368176	122368322
ENSE00001154703	122359591	122359919
ENSE00003474263	122362968	122363027
ENSE00003556423	122383174	122383231
ENSE00003585100	122371675	122371800

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 97.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6498 / max 199.4382, expressed in 1588 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44127	5.6117	1585
44126	0.0381	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.35	gold quality
mucosa of transverse colon	UBERON:0004991	94.77	gold quality
adrenal tissue	UBERON:0018303	94.54	gold quality
rectum	UBERON:0001052	94.19	gold quality
right lobe of liver	UBERON:0001114	93.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.70	gold quality
body of pancreas	UBERON:0001150	93.64	gold quality
muscle of leg	UBERON:0001383	92.39	gold quality
gastrocnemius	UBERON:0001388	92.32	gold quality
right uterine tube	UBERON:0001302	92.23	gold quality
metanephros cortex	UBERON:0010533	92.21	gold quality
pancreas	UBERON:0001264	91.59	gold quality
right adrenal gland	UBERON:0001233	91.47	gold quality
islet of Langerhans	UBERON:0000006	91.33	gold quality
calcaneal tendon	UBERON:0003701	91.03	gold quality
left adrenal gland	UBERON:0001234	90.99	gold quality
transverse colon	UBERON:0001157	90.91	gold quality
esophagus mucosa	UBERON:0002469	90.82	gold quality
left adrenal gland cortex	UBERON:0035825	90.82	gold quality
right adrenal gland cortex	UBERON:0035827	90.75	gold quality
tendon	UBERON:0000043	90.63	gold quality
body of stomach	UBERON:0001161	90.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.63	gold quality
apex of heart	UBERON:0002098	89.55	gold quality
skeletal muscle organ	UBERON:0014892	89.47	gold quality
vermiform appendix	UBERON:0001154	89.44	gold quality
tendon of biceps brachii	UBERON:0008188	89.27	gold quality
adrenal cortex	UBERON:0001235	89.19	gold quality
ventricular zone	UBERON:0003053	89.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting MIX23, 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-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-1269A	92.75	64.61	542
HSA-MIR-1269B	92.75	64.73	538

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Comprehensive pan-cancer analysis reveals CCDC58 as a carcinogenic factor related to immune infiltration. (PMID:38066393)
• CCDC58 is a potential biomarker for diagnosis, prognosis, immunity, and genomic heterogeneity in pan-cancer. (PMID:38609450)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mix23	ENSDARG00000045351
mus_musculus	Mix23	ENSMUSG00000075229
rattus_norvegicus	Mix23	ENSRNOG00000031653
drosophila_melanogaster	Ccdc58	FBGN0036909

Protein

Protein identifiers

Protein MIX23 — Q4VC31 (reviewed: Q4VC31)

Alternative names: Coiled-coil domain-containing protein 58

All UniProt accessions (4): Q4VC31, C9JBU9, C9JQ41, H7C525

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the MIX23 family.

RefSeq proteins (2): NP_001017928, NP_001295255 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019171	MIX23	Family

Pfam: PF09774

UniProt features (6 total): modified residue 2, initiator methionine 1, chain 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4VC31-F1	86.70	0.61

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 (2): 2, 100

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): SHEPARD_CRASH_AND_BURN_MUTANT_UP, WEI_MYCN_TARGETS_WITH_E_BOX, WANG_LMO4_TARGETS_DN, GOCC_MITOCHONDRIAL_ENVELOPE, chr3q21, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, HUANG_DASATINIB_RESISTANCE_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_UP, CTGAGCC_MIR24, MARSON_BOUND_BY_FOXP3_STIMULATED, GOCC_ORGANELLE_ENVELOPE_LUMEN, GOCC_ORGANELLE_ENVELOPE, GSE14415_INDUCED_TREG_VS_FOXP3_KO_INDUCED_TREG_UP, GSE14415_INDUCED_TREG_VS_FAILED_INDUCED_TREG_UP, ARID5B_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial envelope	1
organelle envelope lumen	1

Protein interactions and networks

STRING

1030 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIX23	MRPS35	P82673	601
MIX23	KATNBL1	Q9H079	572
MIX23	ZZEF1	O43149	530
MIX23	CCDC87	Q9NVE4	513
MIX23	TIMM21	Q9BVV7	509
MIX23	TIMM9	Q9Y5J7	496
MIX23	ANO5	Q75V66	494
MIX23	SNX30	Q5VWJ9	479
MIX23	TIMM13	P62206	472
MIX23	ISCA2	Q86U28	463
MIX23	TMEM209	Q96SK2	424
MIX23	CISD1	Q9NZ45	392
MIX23	ANKRD40	Q6AI12	390
MIX23	DCDC2B	A2VCK2	389
MIX23	KGD4	P82909	379

IntAct

25 interactions, top by confidence:

A	B	Type	Score
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
AIFM1	HAX1	psi-mi:“MI:2364”(proximity)	0.420
AIFM1	SEC16A	psi-mi:“MI:2364”(proximity)	0.420
HTRA2	HAX1	psi-mi:“MI:2364”(proximity)	0.420
CEP19	MIX23	psi-mi:“MI:0915”(physical association)	0.400
MIX23	TAMM41	psi-mi:“MI:0914”(association)	0.350
MIX23	ALDH1L1	psi-mi:“MI:0914”(association)	0.350
CHCHD4	HAX1	psi-mi:“MI:0914”(association)	0.350
CHCHD4	PDHX	psi-mi:“MI:0914”(association)	0.350
RAE1	NHERF1	psi-mi:“MI:0914”(association)	0.350
AIFM1	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
COX14	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
COX4I1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
SCO1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
SFXN1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
IMMP2L	MRPL45	psi-mi:“MI:2364”(proximity)	0.270
IMMP1L	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
LACTB	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
OMA1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
PARL	HAX1	psi-mi:“MI:2364”(proximity)	0.270
YME1L1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
IKBKE	MIX23	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (48): CCDC58 (Affinity Capture-RNA), CCDC58 (Co-fractionation), CCDC58 (Co-fractionation), CCDC58 (Co-fractionation), CCDC58 (Co-fractionation), CCDC58 (Co-fractionation), PCBP2 (Co-fractionation), PITPNA (Co-fractionation), STAMBP (Co-fractionation), CCDC58 (Affinity Capture-MS), DNAJC19 (Affinity Capture-MS), AFG3L2 (Affinity Capture-MS), MTFMT (Affinity Capture-MS), PAM16 (Affinity Capture-MS), CYCS (Affinity Capture-MS)

ESM2 similar proteins: A4FUI1, B3DL65, B5FX56, B5X5N3, B5X9S3, F1QN74, F4IK01, O94740, P22468, P47149, P70281, P97357, Q09858, Q0WQE7, Q14D04, Q16VW9, Q2KJI3, Q3SYZ9, Q4R6I5, Q4R7B1, Q4VC31, Q561Q8, Q561X3, Q5M8Y7, Q5XG48, Q5XIR8, Q5XK92, Q5ZLS8, Q5ZMJ7, Q60547, Q61QK6, Q63520, Q68CZ6, Q6DCY9, Q6GPT7, Q6IR70, Q6PBK1, Q6TNU3, Q8C6S9, Q8K2A7

Diamond homologs: A4FUI1, B3DL65, B5FX56, B5X9S3, Q4VC31, Q6GPT7, Q6PBK1, Q8R3Q6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1051 predictions. Top by Δscore:

Variant	Effect	Δscore
3:122365334:A:AC	donor_gain	1.0000
3:122365335:C:CC	donor_gain	1.0000
3:122365335:CTAG:C	donor_gain	1.0000
3:122365468:T:C	acceptor_gain	1.0000
3:122365475:T:TC	acceptor_gain	1.0000
3:122368171:CTTA:C	donor_loss	1.0000
3:122368172:TTA:T	donor_loss	1.0000
3:122368173:TA:T	donor_loss	1.0000
3:122368175:C:CA	donor_loss	1.0000
3:122368319:TCAA:T	acceptor_gain	1.0000
3:122368320:CAA:C	acceptor_gain	1.0000
3:122368320:CAAC:C	acceptor_gain	1.0000
3:122368323:C:CC	acceptor_gain	1.0000
3:122371673:A:AC	donor_gain	1.0000
3:122371674:C:CC	donor_gain	1.0000
3:122371674:CAGA:C	donor_gain	1.0000
3:122373034:CATT:C	acceptor_gain	1.0000
3:122373037:T:TC	acceptor_gain	1.0000
3:122363024:TCAA:T	acceptor_gain	0.9900
3:122363025:CAA:C	acceptor_gain	0.9900
3:122363025:CAAC:C	acceptor_gain	0.9900
3:122363025:CAACT:C	acceptor_loss	0.9900
3:122363026:AACT:A	acceptor_loss	0.9900
3:122363027:ACTG:A	acceptor_loss	0.9900
3:122363028:C:CC	acceptor_gain	0.9900
3:122363029:T:A	acceptor_loss	0.9900
3:122365334:ACTAG:A	donor_gain	0.9900
3:122365335:CTAGC:C	donor_gain	0.9900
3:122365467:C:CC	acceptor_gain	0.9900
3:122365468:T:TC	acceptor_gain	0.9900

AlphaMissense

958 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:122359902:G:C	C134W	1.000
3:122359903:C:G	C134S	1.000
3:122359903:C:T	C134Y	1.000
3:122359904:A:G	C134R	1.000
3:122359904:A:T	C134S	1.000
3:122362974:G:C	S126R	1.000
3:122362974:G:T	S126R	1.000
3:122362976:T:G	S126R	1.000
3:122363005:A:G	L116P	1.000
3:122363012:A:G	S114P	1.000
3:122368299:T:A	R67S	1.000
3:122368299:T:G	R67S	1.000
3:122368300:C:A	R67I	1.000
3:122368300:C:G	R67T	1.000
3:122371693:A:C	C53W	1.000
3:122371694:C:A	C53F	1.000
3:122371694:C:G	C53S	1.000
3:122371694:C:T	C53Y	1.000
3:122371695:A:G	C53R	1.000
3:122371695:A:T	C53S	1.000
3:122371723:A:C	F43L	1.000
3:122371723:A:T	F43L	1.000
3:122371725:A:G	F43L	1.000
3:122371736:G:T	P39Q	1.000
3:122371747:G:C	N35K	1.000
3:122371747:G:T	N35K	1.000
3:122371751:A:G	L34S	1.000
3:122371763:A:T	I30K	1.000
3:122371769:T:A	D28V	1.000
3:122371769:T:G	D28A	1.000

dbSNP variants (sampled 300 via entrez): RS1000077139 (3:122366139 C>T), RS1000103587 (3:122378154 G>A), RS1000111323 (3:122384564 C>A), RS1000300821 (3:122372455 T>C), RS1000374654 (3:122365809 C>T), RS1000533072 (3:122365893 C>G,T), RS1000544319 (3:122384250 G>A,C,T), RS1000599093 (3:122360658 A>C,T), RS1000708777 (3:122367117 G>A), RS1000843751 (3:122384109 C>A,T), RS1000900194 (3:122373184 T>C), RS1001010870 (3:122380014 G>C), RS1001202933 (3:122365739 T>G), RS1001253781 (3:122365439 T>C), RS1001346716 (3:122364352 T>C)

Disease associations

OMIM: gene MIM:620713 | 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
GCST000703_2	Phosphorus levels	4.000000e-09
GCST000769_5	Calcium levels	2.000000e-22
GCST003818_11	Resting heart rate	5.000000e-13
GCST90002397_658	Mean spheric corpuscular volume	8.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004861	phosphorus measurement
EFO:0004838	calcium measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	4
Acetaminophen	decreases expression	2
Valproic Acid	affects expression, increases expression	2
afuresertib	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
cylindrospermopsin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Cannabidiol	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Disulfiram	affects binding, decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3B0	Abcam HEK293T MIX23 KO	Transformed cell line	Female
CVCL_E0I2	Ubigene HeLa MIX23 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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