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): 56 total
• MANE Select transcript: NM_015960

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: 13 — 11 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000370472, ENST00000370476, ENST00000471520, ENST00000493385, ENST00000853283, ENST00000853284, ENST00000853285, ENST00000853286, ENST00000853287, ENST00000853288, ENST00000853289, ENST00000853290, ENST00000968212

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106500	23.5114	1817

Top tissues by expression

286 total, 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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

35 targeting CUTC, 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-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

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

Protein

Protein identifiers

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

All UniProt accessions (3): Q9NTM9, A0A0B4J226, 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 (31 total): strand 12, helix 10, turn 3, mutagenesis site 2, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3IWP	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

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

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

1 pathways

ID	Pathway
R-HSA-936837	Ion transport by P-type ATPases

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

Rollup of top-1 pathways:

Category	Pathways
Ion channel transport	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CUTC	CUTA	O60888	736
CUTC	FMO3	P31513	632
CUTC	KRT74	Q7RTS7	522
CUTC	ARSH	Q5FYA8	510
CUTC	YBEY	P58557	509
CUTC	CUEDC1	Q9NWM3	474
CUTC	ATOX1	O00244	468
CUTC	ENTPD7	Q9NQZ7	436
CUTC	ATP7B	P35670	406
CUTC	COPB1	P53618	398
CUTC	COMMD1	Q8N668	395
CUTC	KRT82	Q9NSB4	394
CUTC	CLPP	Q16740	393
CUTC	COX11	Q9Y6N1	391
CUTC	TAAR5	O14804	390

IntAct

63 interactions, top by confidence:

A	B	Type	Score
SPG21	CUTC	psi-mi:“MI:0915”(physical association)	0.780
CUTC	SPG21	psi-mi:“MI:0915”(physical association)	0.780
CUTC	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
SDCBP	CUTC	psi-mi:“MI:0915”(physical association)	0.720
NADSYN1	CUTC	psi-mi:“MI:0915”(physical association)	0.670
CUTC	BCL6	psi-mi:“MI:0915”(physical association)	0.560
CEP76	CUTC	psi-mi:“MI:0915”(physical association)	0.560
CUTC	GCD7	psi-mi:“MI:0915”(physical association)	0.560
GCD7	CUTC	psi-mi:“MI:0915”(physical association)	0.560
CUTC	XPO7	psi-mi:“MI:0915”(physical association)	0.560
KANK2	CUTC	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	CUTC	psi-mi:“MI:0915”(physical association)	0.560
PICK1	CUTC	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	CUTC	psi-mi:“MI:0915”(physical association)	0.560
CDC37	CUTC	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	CUTC	psi-mi:“MI:0915”(physical association)	0.560
MESD	CUTC	psi-mi:“MI:0915”(physical association)	0.560
CUTC	CUTC	psi-mi:“MI:0915”(physical association)	0.550

BioGRID (40): CUTC (Two-hybrid), CUTC (Two-hybrid), CUTC (Two-hybrid), SPG21 (Two-hybrid), CEP76 (Two-hybrid), LNX1 (Two-hybrid), CUTC (Two-hybrid), NADSYN1 (Two-hybrid), CUTC (Two-hybrid), SPG21 (Two-hybrid), NIF3L1 (Two-hybrid), NUDT18 (Two-hybrid), CUTC (Affinity Capture-RNA), CUTC (Two-hybrid), CUTC (Two-hybrid)

ESM2 similar proteins: A0RBL2, A4IPP2, A4WBM9, A6T4L2, A7GMU1, A7Z2G6, A9MUB2, A9VLG7, B1YLS2, B4SVF7, B4T805, B4TYT0, B4U2K6, B5BH48, B5F3I3, B5FSM4, B5R144, B5R8D0, B5XPZ4, B5Y1W9, B7JFY5, B9IUZ0, C0MGL4, C1EMA9, C3L9Q7, C3P4Z6, C5D2V7, C6DFE1, D2QS27, O32179, P35146, P36923, P73618, Q03LH6, Q21VV5, Q3A2I0, Q5KY94, Q5M0M2, Q5M558, Q5P8W0

Diamond homologs: A1AC35, A1JRM5, A4TJL0, A4WBM9, A5F8U2, A6L8P3, A6TB41, A6UF02, A7FID5, A7MT89, A7ZN00, A8A176, A8AFG8, A8GFJ9, A9MUB2, A9QYY3, B0RQ55, B0URL9, B1J0L4, B1JLM0, B1LCZ7, B1XHE2, B2K314, B2RIS4, B2U4X5, B2VJB9, B4ETN7, B4SVF7, B4T805, B4TYT0, B5BH48, B5F3I3, B5F9Z0, B5FSM4, B5R144, B5R8D0, B5XPZ4, B5YR19, B6EK72, B6I1F2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2463 predictions. Top by Δscore:

Variant	Effect	Δscore
10:99704540:ATCCT:A	acceptor_gain	1.0000
10:99716458:TTCC:T	acceptor_gain	1.0000
10:99716459:TCC:T	acceptor_gain	1.0000
10:99716459:TCCC:T	acceptor_loss	1.0000
10:99716460:CC:C	acceptor_gain	1.0000
10:99716460:CCC:C	acceptor_gain	1.0000
10:99716461:CC:C	acceptor_gain	1.0000
10:99716462:C:CC	acceptor_gain	1.0000
10:99716462:CTGC:C	acceptor_loss	1.0000
10:99716463:T:A	acceptor_loss	1.0000
10:99721064:GGCAA:G	acceptor_gain	1.0000
10:99721066:CAA:C	acceptor_gain	1.0000
10:99721069:C:CC	acceptor_gain	1.0000
10:99721070:T:C	acceptor_loss	1.0000
10:99721075:A:C	acceptor_gain	1.0000
10:99724122:CC:C	acceptor_gain	1.0000
10:99724123:CC:C	acceptor_gain	1.0000
10:99724134:C:CT	acceptor_gain	1.0000
10:99724134:C:T	acceptor_gain	1.0000
10:99724135:A:T	acceptor_gain	1.0000
10:99727433:ATACT:A	donor_loss	1.0000
10:99727434:TACTT:T	donor_loss	1.0000
10:99727435:ACTT:A	donor_loss	1.0000
10:99727436:CTT:C	donor_loss	1.0000
10:99727437:TTA:T	donor_loss	1.0000
10:99727438:TACA:T	donor_loss	1.0000
10:99727439:A:AC	donor_gain	1.0000
10:99727440:C:CA	donor_loss	1.0000
10:99727440:C:CG	donor_gain	1.0000
10:99727440:CA:C	donor_gain	1.0000

AlphaMissense

1744 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:99743224:T:C	F89L	0.997
10:99743226:T:A	F89L	0.997
10:99743226:T:G	F89L	0.997
10:99736297:C:A	A38D	0.996
10:99736305:G:C	A41P	0.996
10:99739719:G:C	R48P	0.996
10:99754591:C:G	H222D	0.996
10:99736296:G:C	A38P	0.995
10:99744070:G:C	R146P	0.995
10:99747335:G:A	G173E	0.995
10:99736284:T:C	S34P	0.994
10:99739726:A:C	E50D	0.994
10:99739726:A:T	E50D	0.994
10:99743309:G:A	G117E	0.993
10:99747262:G:C	D149H	0.993
10:99747326:T:C	L170S	0.993
10:99747358:G:T	G181W	0.993
10:99754538:T:A	I204K	0.993
10:99744066:C:G	H145D	0.992
10:99747380:T:C	L188P	0.992
10:99736277:T:G	C31W	0.991
10:99736306:C:A	A41E	0.991
10:99739728:T:C	L51S	0.991
10:99739763:A:C	S63R	0.991
10:99739765:C:A	S63R	0.991
10:99739765:C:G	S63R	0.991
10:99743213:G:C	R85P	0.991
10:99743225:T:C	F89S	0.991
10:99747263:A:C	D149A	0.991
10:99747263:A:T	D149V	0.991

dbSNP variants (sampled 300 via entrez): RS1000008782 (10:99738468 A>G), RS1000205963 (10:99733181 C>T), RS1000236663 (10:99745237 T>C,G), RS1000247549 (10:99738160 T>A,C), RS1000334891 (10:99752869 A>G), RS1000337477 (10:99752669 G>A,T), RS1000370250 (10:99752341 C>T), RS1000372928 (10:99752553 C>G), RS1000478160 (10:99745627 G>T), RS1000489489 (10:99732367 T>C,G), RS1000498503 (10:99744258 T>C), RS1000584849 (10:99736612 A>C,T), RS1001025360 (10:99740637 C>G,T), RS1001033047 (10:99733512 C>G), RS1001167366 (10:99753226 A>C)

Disease associations

OMIM: gene MIM:610101 | 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
GCST001438_10	Crohn’s disease	5.000000e-07
GCST001762_86	Obesity-related traits	6.000000e-06
GCST003017_4	Colorectal cancer	8.000000e-07
GCST003017_9	Colorectal cancer	4.000000e-08

EFO canonical traits (1, from GWAS)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

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	affects cotreatment, increases expression	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)

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