CUTC

Summary

CUTC (cutC copper transporter, HGNC:24271) is a protein-coding gene on chromosome 10q24.2, encoding Copper homeostasis protein cutC homolog (Q9NTM9). May play a role in copper homeostasis.

Members of the CUT family of copper transporters are associated with copper homeostasis and are involved in the uptake, storage, delivery, and efflux of copper (Gupta et al., 1995 [PubMed 7635807]; Li et al., 2005 [PubMed 16182249]).

Source: NCBI Gene 51076 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 58 total
• GTEx eGene: eQTL in 13 tissues, sQTL in 3 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.22 (unconstrained)
• MANE Select transcript: NM_015960
• Notable: 58 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24271
Approved symbol	CUTC
Name	cutC copper transporter
Location	10q24.2
Locus type	gene with protein product
Status	Approved
Aliases	CGI-32
Ensembl gene	ENSG00000119929
Ensembl biotype	protein_coding
OMIM	610101
Entrez	51076

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 20 protein_coding, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000370476

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1, TSL 5: 1

ENST00000370476, ENST00000370472, ENST00000471520, ENST00000493385, ENST00000853283, ENST00000853284, ENST00000853285, ENST00000853286, ENST00000853287, ENST00000853288, ENST00000853289, ENST00000853290, ENST00000968212, ENST00001001736, ENST00001001737, ENST00001001738, ENST00001001739, ENST00001001740, ENST00001057139, ENST00001057141, ENST00001101328, ENST00001110767, ENST00001110768, ENST00001112609, ENST00001121109, ENST00001121110, ENST00001121111, ENST00001136831

RefSeq mRNA: 1 — MANE Select: NM_015960 NM_015960

CCDS: CCDS7483

Canonical transcript exons

ENST00000370476 — 9 exons

Exon	Start	End
ENSE00000719678	99743153	99743362
ENSE00000719686	99747257	99747390
ENSE00001020182	99744037	99744072
ENSE00001020185	99750369	99750396
ENSE00001452813	99755625	99756134
ENSE00001452815	99732234	99732409
ENSE00003522076	99754529	99754634
ENSE00003587758	99739710	99739769
ENSE00003638058	99736246	99736317

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.5114 / max 351.8301, expressed in 1817 samples.

Highest expression (Bgee): skeletal muscle tissue of rectus abdominis, hindlimb stylopod muscle, biceps brachii, skeletal muscle tissue of biceps brachii, gastrocnemius.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CUTC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	7.3e-18	+0.18	10:99738639:T:G
Testis	sqtl	1.2e-08	-0.46	10:99760577:G:A
Adipose Subcutaneous	eqtl	7.4e-07	-0.15	10:99787285:C:T
Whole Blood	eqtl	2.6e-04	-0.19	10:99822469:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.1e-04	+0.14	10:99752337:A:C
Skin Sun Exposed Lower leg	eqtl	3.2e-04	-0.13	10:99746626:A:G
Skin Sun Exposed Lower leg	sqtl	9.9e-04	-0.27	10:99630733:G:A
Brain Putamen basal ganglia	eqtl	7.0e-03	+0.38	10:100710675:C:T
Brain Cortex	eqtl	7.7e-03	-0.59	10:100018750:C:A
Esophagus Mucosa	eqtl	2.0e-02	-0.27	10:99818560:C:T
Thyroid	eqtl	3.5e-02	+0.10	10:99875704:T:A
Heart Left Ventricle	eqtl	3.9e-02	-0.16	10:99999225:A:C
Brain Cerebellar Hemisphere	sqtl	4.2e-02	+0.67	10:100010620:C:G
Brain Hippocampus	eqtl	4.3e-02	-0.29	10:100722427:C:T
Cells Cultured fibroblasts	eqtl	4.4e-02	+0.15	10:99606268:A:G
Stomach	eqtl	4.5e-02	+0.44	10:100143392:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
106500	23.5114	1817

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.04	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.64	gold quality
biceps brachii	UBERON:0001507	98.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.37	gold quality
gastrocnemius	UBERON:0001388	98.33	gold quality
vastus lateralis	UBERON:0001379	98.27	gold quality
quadriceps femoris	UBERON:0001377	98.21	gold quality
skeletal muscle tissue	UBERON:0001134	98.16	gold quality
muscle organ	UBERON:0001630	98.15	gold quality
muscle of leg	UBERON:0001383	98.12	gold quality
deltoid	UBERON:0001476	97.75	gold quality
triceps brachii	UBERON:0001509	97.75	gold quality
gluteal muscle	UBERON:0002000	97.67	gold quality
diaphragm	UBERON:0001103	96.78	gold quality
tibialis anterior	UBERON:0001385	96.11	gold quality
body of tongue	UBERON:0011876	95.85	gold quality
muscle tissue	UBERON:0002385	94.96	gold quality
left testis	UBERON:0004533	93.65	gold quality
right testis	UBERON:0004534	93.32	gold quality
apex of heart	UBERON:0002098	92.95	gold quality
testis	UBERON:0000473	92.71	gold quality
heart left ventricle	UBERON:0002084	92.55	gold quality
cardiac ventricle	UBERON:0002082	92.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.20	gold quality
mucosa of stomach	UBERON:0001199	91.67	gold quality
oocyte	CL:0000023	91.48	gold quality
tibial nerve	UBERON:0001323	91.24	gold quality
heart	UBERON:0000948	90.57	gold quality
adipose tissue	UBERON:0001013	90.55	gold quality
right atrium auricular region	UBERON:0006631	90.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.24	gold quality
connective tissue	UBERON:0002384	90.13	gold quality
omental fat pad	UBERON:0010414	90.04	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.02	gold quality
peritoneum	UBERON:0002358	89.99	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.95	gold quality
popliteal artery	UBERON:0002250	89.74	gold quality
tibial artery	UBERON:0007610	89.74	gold quality
heart right ventricle	UBERON:0002080	89.66	gold quality
spleen	UBERON:0002106	89.62	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.39	gold quality
lower esophagus	UBERON:0013473	89.36	gold quality
monocyte	CL:0000576	89.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.26	gold quality
cardiac atrium	UBERON:0002081	89.23	gold quality
leukocyte	CL:0000738	89.22	gold quality
right lobe of liver	UBERON:0001114	89.22	gold quality
calcaneal tendon	UBERON:0003701	89.19	gold quality
mononuclear cell	CL:0000842	89.18	gold quality
granulocyte	CL:0000094	89.01	gold quality
right lung	UBERON:0002167	89.01	gold quality
tongue	UBERON:0001723	88.87	gold quality
descending thoracic aorta	UBERON:0002345	88.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.60	gold quality
left uterine tube	UBERON:0001303	88.58	gold quality
aorta	UBERON:0000947	88.56	gold quality
skin of leg	UBERON:0001511	88.33	gold quality
spinal cord	UBERON:0002240	88.31	gold quality
right adrenal gland cortex	UBERON:0035827	88.21	gold quality
rectum	UBERON:0001052	87.95	gold quality
ectocervix	UBERON:0012249	87.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.77	gold quality
endocervix	UBERON:0000458	87.75	gold quality
esophagus	UBERON:0001043	87.69	gold quality
left adrenal gland	UBERON:0001234	87.58	gold quality
right adrenal gland	UBERON:0001233	87.47	gold quality
minor salivary gland	UBERON:0001830	87.47	gold quality
left coronary artery	UBERON:0001626	87.40	gold quality
left adrenal gland cortex	UBERON:0035825	87.39	gold quality
body of stomach	UBERON:0001161	87.29	gold quality
skin of abdomen	UBERON:0001416	87.28	gold quality
body of uterus	UBERON:0009853	87.27	gold quality
thoracic aorta	UBERON:0001515	87.22	gold quality
ascending aorta	UBERON:0001496	87.12	gold quality
synovial joint	UBERON:0002217	86.96	gold quality
nucleus accumbens	UBERON:0001882	86.92	gold quality
ventricular zone	UBERON:0003053	86.87	gold quality
small intestine	UBERON:0002108	86.84	gold quality
lymph node	UBERON:0000029	86.81	gold quality
transverse colon	UBERON:0001157	86.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.66	gold quality
urinary bladder	UBERON:0001255	86.57	gold quality
gall bladder	UBERON:0002110	86.52	gold quality
islet of Langerhans	UBERON:0000006	86.48	gold quality
vagina	UBERON:0000996	86.46	gold quality
right lobe of thyroid gland	UBERON:0001119	86.41	gold quality
blood	UBERON:0000178	86.39	gold quality
adrenal cortex	UBERON:0001235	86.39	gold quality
body of pancreas	UBERON:0001150	86.37	gold quality
adrenal gland	UBERON:0002369	86.37	gold quality
coronary artery	UBERON:0001621	86.32	gold quality
esophagus mucosa	UBERON:0002469	86.32	gold quality
upper lobe of left lung	UBERON:0008952	86.27	gold quality
secondary oocyte	CL:0000655	86.18	gold quality
anterior cingulate cortex	UBERON:0009835	86.17	gold quality
colonic epithelium	UBERON:0000397	86.16	gold quality
cingulate cortex	UBERON:0003027	86.04	gold quality
caudate nucleus	UBERON:0001873	85.90	gold quality
multicellular organism	UBERON:0000468	85.84	gold quality
stromal cell of endometrium	CL:0002255	85.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	427.30
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	361.4	high
Tongue	tissue	190.9
Testis	tissue	38.0	high
Heart muscle	tissue	33.9	medium
Adipose tissue	tissue	29.5	medium
Liver	tissue	28.2	medium
Retina	tissue	26.2
Breast	tissue	23.7	medium
Thymus	tissue	22.3
Bone marrow	tissue	22.3	low
Lymph node	tissue	20.9	low
Spleen	tissue	20.7	not detected
Tonsil	tissue	18.5	low
Nucleus accumbens	tissue	16.8
Vagina	tissue	16.0	medium
Urinary bladder	tissue	15.6	medium
Rectum	tissue	14.9	medium
Esophagus	tissue	14.8	low
Appendix	tissue	13.8	low
Prostate	tissue	13.6	low
Smooth muscle	tissue	13.5	low
Small intestine	tissue	12.7	medium
Hippocampus	tissue	12.7	low
Kidney	tissue	12.3	medium
Lung	tissue	12.1	medium
Colon	tissue	12.0	medium
Locus coeruleus	tissue	11.8
Cervix	tissue	11.7	medium
Postcentral gyrus	tissue	11.4
Gallbladder	tissue	11.3	medium
Ovary	tissue	10.8	low
Placenta	tissue	10.6	not detected
Seminal vesicle	tissue	10.5	low
Endometrium 1	tissue	10.4	not detected
Epididymis	tissue	10.4	low
Duodenum	tissue	10.4	medium
Choroid plexus	tissue	10.3
Adrenal gland	tissue	10.3	medium
Skin 1	tissue	10.0	medium
Thyroid gland	tissue	9.6	medium
Salivary gland	tissue	9.4	medium
Stomach 1	tissue	9.3	medium
Fallopian tube	tissue	9.2	medium
Caudate putamen	tissue	9.2
Frontal cortex	tissue	8.3
Cerebellum	tissue	8.3	medium
Parathyroid gland	tissue	8.1	low
Olfactory bulb	tissue	8.0
Septum	tissue	7.7
Amygdala	tissue	7.6
Corpus callosum	tissue	7.6
Pituitary gland	tissue	7.5
Hippocampal formation	tissue	7.5
Entorhinal cortex	tissue	7.5
Pancreas	tissue	7.4	medium
Cerebral cortex	tissue	7.3	medium
Pons	tissue	7.3
Periaqueductal gray	tissue	7.3
Retrosplenial cortex	tissue	7.3
Medulla oblongata	tissue	7.2

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Corpus callosum, genu (white matter) (25.8), Parieto-temporal junction (white matter) (25.4), Corpus callosum, splenium (white matter) (24.3), Temporal white matter (22.4), Cerebellar white matter (21.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

Targeting CUTC by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 35 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-219B-3P	97.31	66.96	672

Functional genomics

gnomAD constraint: pLI 1.25e-05, LOEUF 1.22, missense Z 0.324 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000370476 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 3)

• Cloning, expression and subcellular localization of CutC. (PMID:16182249)
• Results suggest that hCutC functions as an enzyme with Cu(I) as a cofactor rather than a copper transporter and the potential Cu(I)-binding site consists of the two Cys residues and other conserved residues in the vicinity. (PMID:19878721)
• present study reveals copper induced damage in cells upon hCutC silencing and provides evidence for the role of hCutC protein in intracellular copper homeostasis (PMID:26660891)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cutc	ENSDARG00000077306
mus_musculus	Cutc	ENSMUSG00000025193
rattus_norvegicus	Cutc	ENSRNOG00000017298
drosophila_melanogaster	CG6136	FBGN0038332
caenorhabditis_elegans		WBGENE00022702

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Escherichia coli APEC O1	A1AC35	100.0%	Diamond
Yersinia pestis Pestoides F	A4TJL0	100.0%	Diamond
Vibrio cholerae O395	A5F8U2	100.0%	Diamond
Escherichia coli O139:H28 str. E24377A	A7ZN00	100.0%	Diamond
Escherichia coli HS	A8A176	100.0%	Diamond
Escherichia coli ATCC 8739	B1J0L4	100.0%	Diamond
Escherichia coli str. K-12 substr. DH10B	B1XHE2	100.0%	Diamond
Yersinia pseudotuberculosis PB1/+	B2K314	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Paratyphi A str. AKU_12601	B5BH48	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Agona str. SL483	B5F3I3	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Dublin str. CT_02021853	B5FSM4	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Enteritidis str. P125109	B5R144	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Gallinarum str. 287/91	B5R8D0	100.0%	Diamond
Escherichia coli O157:H7 str. EC4115	B5YR19	100.0%	Diamond
Escherichia coli SE11	B6I1F2	100.0%	Diamond
Escherichia coli IAI1	B7M2G5	100.0%	Diamond
Escherichia coli S88	B7MBT3	100.0%	Diamond
Escherichia coli O127:H6 str. E2348/69	B7USQ1	100.0%	Diamond
Caulobacter vibrioides NA1000	B8GZC1	100.0%	Diamond
Vibrio cholerae M66-2	C3LSY3	100.0%	Diamond
Escherichia coli BW2952	C4ZQF8	100.0%	Diamond
Shigella flexneri	P67825	100.0%	Diamond
Escherichia coli K-12	P67826	100.0%	Diamond
Shigella flexneri 5 str. 8401	Q0T3Q3	100.0%	Diamond
Escherichia coli 536	Q0TGV9	100.0%	Diamond
Yersinia pestis Antiqua	Q1C825	100.0%	Diamond
Yersinia pestis Nepal516	Q1CJH5	100.0%	Diamond
Escherichia coli UTI89	Q1RAR0	100.0%	Diamond
Shigella sonnei Ss046	Q3Z2Q2	100.0%	Diamond
Xanthomonas campestris pv. campestris str. 8004	Q4UXF8	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Paratyphi A str. ATCC 9150	Q5PMZ0	100.0%	Diamond
Yersinia pseudotuberculosis IP 32953	Q66AU9	100.0%	Diamond
Escherichia coli CFT073	Q8FGQ2	100.0%	Diamond
Xanthomonas campestris pv. campestris str. ATCC 33913	Q8P6Q4	100.0%	Diamond
Escherichia coli O157:H7	Q8XCH4	100.0%	Diamond
Yersinia pestis	Q8ZEV5	100.0%	Diamond
Salmonella enterica subsp. enterica serovar Typhimurium str. LT2	Q8ZNV0	100.0%	Diamond
Caulobacter vibrioides CB15	Q9A5T7	100.0%	Diamond
Vibrio cholerae O1 biovar El Tor str. N16961	Q9KU00	100.0%	Diamond
Yersinia pseudotuberculosis IP 31758	A7FID5	99.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ABCC2	protein-coding	1244
DNMBP	protein-coding	23268
SLC25A28-DT	ncRNA	123466211
COX15	protein-coding	1355
ENTPD7	protein-coding	57089
SLC25A28	protein-coding	81894
DNMBP-AS1	ncRNA	100188954
CPN1	protein-coding	1369
NKX2-3	protein-coding	159296

Protein

Protein identifiers

Copper homeostasis protein cutC homolog — Q9NTM9 (reviewed: Q9NTM9)

All UniProt accessions (3): A0A0B4J226, Q9NTM9, Q5TCZ7

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in copper homeostasis. Can bind one Cu(1+) per subunit.

Subunit / interactions. Homotetramer.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the CutC family.

RefSeq proteins (1): NP_057044* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005627	CutC-like	Family
IPR036822	CutC-like_dom_sf	Homologous_superfamily

Pfam: PF03932

UniProt features (32 total): strand 12, helix 11, turn 3, mutagenesis site 2, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
3IWP	Crystal structure of human copper homeostasis protein CutC	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NTM9-F1	91.70	0.86

Human Protein Atlas

Protein class: Transporters, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm; nucleoli

Antibody reliability (HPA): IH enhanced · IF enhanced

Functional residue map

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

Mutagenesis-validated functional residues (2)

Position	Phenotype
31	reduces copper binding. reduces copper binding by 75%; when associated with a-52.
52	reduces copper binding. reduces copper binding by 75%; when associated with a-31.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-983712	Ion channel transport	—
R-HSA-936837	Ion transport by P-type ATPases	electronic
R-HSA-382551	Transport of small molecules	—

MSigDB gene sets: 136 (showing top): GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_COPPER_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_MONOATOMIC_ION_HOMEOSTASIS, NRF2_01, GOBP_COPPER_ION_HOMEOSTASIS, GOBP_PROTEIN_TETRAMERIZATION, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOCC_NUCLEOLUS, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B

GO Biological Process (3): copper ion transport (GO:0006825), protein tetramerization (GO:0051262), copper ion homeostasis (GO:0055070)

GO Molecular Function (3): copper ion binding (GO:0005507), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Ion channel transport	1
Transport of small molecules	1

GO top-level categories

13 GO namespaces:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
transition metal ion transport	1
protein complex oligomerization	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
protein tetramerization	BP	physical interaction
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
copper ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 580 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CUTC	CUTA	O60888	659
CUTC	FMO3	P31513	653
CUTC	ARSD	P51689	523
CUTC	ARSH	Q5FYA8	491
CUTC	ATOX1	O00244	477
CUTC	COMMD1	Q8N668	449
CUTC	KRT74	Q7RTS7	431
CUTC	COPB1	P53618	430
CUTC	COX11	Q9Y6N1	415
CUTC	YBEY	P58557	411
CUTC	CUEDC1	Q9NWM3	404
CUTC	NR1H4	Q96RI1	388
CUTC	DNAJC21	Q5F1R6	381
CUTC	ACOT13	Q9NPJ3	380
CUTC	GNL1	P36915	380

IntAct

Human interaction partners of CUTC in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

20 partners by confidence:

Partner	Interaction type	MIscore	Records
SPG21	physical association	0.780	8
SDCBP	physical association	0.720	6
NADSYN1	physical association	0.670	4
ATXN1	physical association	0.560	3
BCL6	physical association	0.560	3
CDC37	physical association	0.560	3
CEP76	physical association	0.560	3
GCD7	physical association	0.560	3
KANK2	physical association	0.560	3
MEOX2	physical association	0.560	3
MESD	physical association	0.560	3
NTAQ1	physical association	0.560	3
PICK1	physical association	0.560	3
XPO7	physical association	0.560	1
LNX1	physical association	0.550	2
CFTR	physical association	0.370	1
ECE1	physical association	0.370	1
SLC35C1	association	0.350	1
ASCC2	physical association	0.000	1
SLC25A6	physical association	0.000	1

BioGRID (42 interactions; top human partners by supporting records): SPG21 (Two-hybrid; 3 records), NADSYN1 (Two-hybrid; 2 records), SDCBP (Two-hybrid; 2 records), ASCC2 (Two-hybrid), ATXN1 (Two-hybrid), BCL6 (Two-hybrid), CDC37 (Two-hybrid), CEMIP (Affinity Capture-MS), CEP76 (Two-hybrid), CFTR (PCA), GABPA (Co-fractionation), GANAB (Co-fractionation), IRF2BP2 (Co-fractionation), KANK2 (Two-hybrid), LIMCH1 (Co-fractionation)

Disease & clinical

Genetic variants

Variant evidence for CUTC: 58 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	2
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 706):

Position(s)	Effect	Δscore	Sites
10:99732333	donor_gain	1.0000
10:99732402	donor_gain	1.0000
10:99736244–99736245	acceptor_loss	1.0000	5
10:99736318–99736319	donor_loss	1.0000	4
10:99739708–99739709	acceptor_loss	1.0000	6
10:99739770–99739771	donor_loss	1.0000	5
10:99743151–99743152	acceptor_loss	1.0000	5
10:99743344	donor_gain	1.0000
10:99743363–99743364	donor_loss	1.0000	5
10:99747255–99747256	acceptor_loss	1.0000	5

AlphaMissense

660 missense substitutions predicted likely pathogenic (of 1,744 scored), across 176 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M233	9	0.828	0.948
M99	9	0.815	0.986
D149	8	0.985	0.993
H222	8	0.968	0.996
F89	8	0.964	0.997
H145	8	0.962	0.992
D88	8	0.919	0.973
F144	8	0.904	0.989
F148	8	0.891	0.987
D102	8	0.881	0.971
S172	8	0.861	0.991
D33	8	0.839	0.959
E29	7	0.976	0.989
E50	7	0.960	0.994
C31	7	0.946	0.991
C52	7	0.945	0.987
M81	7	0.892	0.987
F79	7	0.876	0.978
F221	7	0.867	0.990
E95	7	0.859	0.975

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	0.000122

Disease associations

OMIM: gene MIM:610101 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST003017_9	Colorectal cancer	4e-8
GCST001438_10	Crohn’s disease	5e-7
GCST003017_4	Colorectal cancer	8e-7
GCST001762_61	Obesity-related traits	6e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Fluorouracil	affects response to substance, affects reaction, decreases expression	2
Copper Sulfate	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
trichostatin A	affects expression	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Quercetin	decreases expression	1
Selenium	affects cotreatment, increases expression, decreases expression	1
Silicon Dioxide	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1PM	Abcam HeLa CUTC KO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

14 trials:

NCT	Phase	Status	Title
NCT01721733	Phase 2	COMPLETED	Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome
NCT02352896	Phase 2	COMPLETED	Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome
NCT03747328	Phase 2	WITHDRAWN	ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
NCT06843811	Phase 2	ENROLLING_BY_INVITATION	Sirolimus for Leigh Syndrome
NCT06990984	Phase 2	NOT_YET_RECRUITING	A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS)
NCT02544217	Phase 1	COMPLETED	A Dose-escalating Clinical Trial With KH176
NCT04378075	Phase 2/3	TERMINATED	A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy
NCT01780168	Not specified	RECRUITING	The NIH MINI Study: Metabolism, Infection, and Immunity in Inborn Errors of Metabolism
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01803906	Not specified	ENROLLING_BY_INVITATION	Tissue Sample Study for Mitochondrial Disorders
NCT03137355	Not specified	RECRUITING	The International Registry for Leigh Syndrome
NCT05277363	Not specified	WITHDRAWN	A Study of the Natural Course of SURF1 Deficiency
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT06967831	Not specified	RECRUITING	Drug Repurposing for Mitochondrial Disorders Using iPSCs Derived Neural Cells