CCS

Summary

CCS (copper chaperone for superoxide dismutase, HGNC:1613) is a protein-coding gene on chromosome 11q13.2, encoding Copper chaperone for superoxide dismutase (O14618). Delivers copper to copper zinc superoxide dismutase (SOD1).

Copper chaperone for superoxide dismutase specifically delivers Cu to copper/zinc superoxide dismutase and may activate copper/zinc superoxide dismutase through direct insertion of the Cu cofactor.

Source: NCBI Gene 9973 — RefSeq curated summary.

At a glance

• Gene–disease (curated): disorder of copper metabolism (No Known Disease Relationship, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_005125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1613
Approved symbol	CCS
Name	copper chaperone for superoxide dismutase
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000173992
Ensembl biotype	protein_coding
OMIM	603864
Entrez	9973

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000310190, ENST00000525435, ENST00000526058, ENST00000526066, ENST00000530384, ENST00000530961, ENST00000531990, ENST00000533244, ENST00000534763, ENST00000867839, ENST00000939538

RefSeq mRNA: 1 — MANE Select: NM_005125 NM_005125

CCDS: CCDS8146

Canonical transcript exons

ENST00000533244 — 8 exons

Exon	Start	End
ENSE00001188299	66599459	66599636
ENSE00001188303	66599116	66599253
ENSE00002158477	66605702	66606019
ENSE00002179838	66593185	66593300
ENSE00003574585	66593642	66593714
ENSE00003664359	66605339	66605416
ENSE00003675175	66605489	66605592
ENSE00003691875	66600489	66600549

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2377 / max 254.8752, expressed in 1816 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115348	13.7697	1809
115349	5.0113	1712
115347	1.0932	773
115350	0.3635	135

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.66	gold quality
right ovary	UBERON:0002118	96.50	gold quality
left ovary	UBERON:0002119	96.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.21	gold quality
right adrenal gland	UBERON:0001233	96.16	gold quality
right adrenal gland cortex	UBERON:0035827	96.16	gold quality
left adrenal gland cortex	UBERON:0035825	95.89	gold quality
apex of heart	UBERON:0002098	95.80	gold quality
left adrenal gland	UBERON:0001234	95.71	gold quality
granulocyte	CL:0000094	95.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.53	gold quality
adenohypophysis	UBERON:0002196	95.50	gold quality
right testis	UBERON:0004534	95.45	gold quality
mucosa of transverse colon	UBERON:0004991	95.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.39	gold quality
lower esophagus	UBERON:0013473	95.38	gold quality
right lobe of thyroid gland	UBERON:0001119	95.35	gold quality
endocervix	UBERON:0000458	95.31	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.25	gold quality
body of uterus	UBERON:0009853	95.19	gold quality
left testis	UBERON:0004533	95.17	gold quality
adrenal cortex	UBERON:0001235	95.03	gold quality
mucosa of stomach	UBERON:0001199	95.01	gold quality
transverse colon	UBERON:0001157	94.82	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.76	gold quality
left lobe of thyroid gland	UBERON:0001120	94.72	gold quality
body of stomach	UBERON:0001161	94.70	gold quality
right atrium auricular region	UBERON:0006631	94.64	gold quality
left uterine tube	UBERON:0001303	94.63	gold quality
spleen	UBERON:0002106	94.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting CCS, 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-5582-3P	99.86	72.48	4221
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-2276-5P	96.27	65.85	937

Literature-anchored findings (GeneRIF, showing 30)

• No causative mutations for amyotrophic lateral sclerosis (ALS) gene have been detected in the CCS gene in 20 sporadic ALS patients analyzed, but an intragenic single nucleotide polymorphism has been identified. (PMID:11991808)
• Study of site-directed cysteine-to-serine mutants of CCS suggests the formation of a domain III copper cluster within a dimeric or tetrameric protein and further suggest that this cluster may be an important element of CCS copper transfer machinery. (PMID:15736924)
• The copper chaperone CCS is responsible for copper insertion into apo-superoxide dismutasse 1. (PMID:16132821)
• A mechanism determining the abundance of CCS that is competitive with the process of copper delivery to SOD1 is described, revealing a unique post-translational component of intracellular copper homeostasis. (PMID:16531609)
• copper chaperone mRNA levels were reduced in peripheral mononuclear cells after copper supplementation (PMID:17683925)
• Measurements of hCCS-induced SOD1 activation were used to show that the C-terminal CXC sequence is both necessary and sufficient for EZn-SOD maturation. (PMID:18393442)
• copper chaperone for SOD1 (CCS) facilitates maturation of SOD1 and that CCS overexpression ameliorates intracellular aggregation of mutant SOD1 in vivo. (PMID:18552350)
• data suggest that Cys residues in domain 2 of hCCS are involved in the formation, stability, and redox potential of the domain 3 cluster (PMID:19007184)
• Incomplete posttranslational modification of nascent superoxide dismutase (SOD)1 polypeptides via trasnsgenic SOD1 copper chaperone (CCS) may be a characteristic shared by familial SOD1 mutants in amyotrophic lateral sclerosis. (PMID:19227972)
• Results describe the identification of the copper chaperone for superoxide dismutase as a mediator of copper delivery to XIAP in cells. (PMID:20154138)
• Loss of copper chaperone for superoxide dismutase (CCS) increases amyloid-beta production in both CCS knockout neurons and CCS small-interfering (si)RNA-treated cultured tumor cells. (PMID:20693630)
• CCS reduces, under non-oxidative conditions, yet facilitates in the presence of H(2)O(2), mitochondrial translocation of inactive SOD1 mutants. (PMID:21354101)
• The results of the present study reveal the plasticity of this multi-domain chaperone in solution and are consistent with an indispensable flexibility necessary for executing its dual functions of metal binding and transfer. (PMID:21722094)
• The CCS mutation, p.Arg163Trp, causes reduced SOD1 activity and may impair other mechanisms important for normal Cu homeostasis. (PMID:22508683)
• analysis of human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS) (PMID:22869735)
• CCS-1 facilitates copper trafficking to the mitochondria, but does not affect the transfer of copper to the cytochrome c oxidase. (PMID:23900152)
• CCS1 serves as a specialized import receptor in mitochondria that facilitates the import and folding of SOD1 and CCS1. (PMID:24026195)
• CCS-dependent copper acquisition and distribution largely occur at membrane interfaces and that this emerging role of the bilayer may reflect a general mechanistic aspect of cellular transition metal ion acquisition. (PMID:24297923)
• CTR1 silencing increased the protein levels of copper chaperone ATOX1 and copper chaperone for superoxide dismutase 1 (CCS-1), but decreased copper chaperone for cytochrome c oxidase (COX17). (PMID:24343031)
• CCS mRNA and protein levels in the serum are not correlated with inflammatory processes. (PMID:24855044)
• Coexpression of hCCS in the presence of copper restores the correct maturation of the SOD1 mutants and prevents the formation of the unstructured species, confirming that hCCS also acts as a molecular chaperone. (PMID:25429517)
• Human cytoplasmic copper chaperones Atox1 and CCS exchange copper ions in vitro (PMID:25673218)
• In addition to Atox1, the human cytoplasm also contains Cu chaperones for loading of superoxide dismutase 1 (i.e. CCS) and cytochrome c oxidase in mitochondria (i.e. Cox17). [review] (PMID:26745464)
• CCS-D2 forms a stable complex with zinc-bound SOD1 in human cells, that has a twofold stabilizing effect: it both prevents the accumulation of unstructured mutant SOD1 and promotes zinc binding. CCS-D2 interacts with apo-SOD1 in vitro, suggesting that in cells CCS stabilizes mutant apo-SOD1 prior to zinc binding. (PMID:29234142)
• Molecular recognition and maturation of SOD1 by its evolutionarily destabilized cognate chaperone CCS has been reported. (PMID:30735496)
• Here, we show that DCAC50, a recently developed small-molecule inhibitor of the intracellular copper chaperones, ATOX1 and CCS, reduces cell proliferation and elevates oxidative stress, triggering apoptosis in a panel of triple-negative breast cancer (TNBC) cells. (PMID:30824611)
• Mutations in Superoxide Dismutase 1 (Sod1) Linked to Familial Amyotrophic Lateral Sclerosis Can Disrupt High-Affinity Zinc-Binding Promoted by the Copper Chaperone for Sod1 (Ccs). (PMID:32121118)
• The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation. (PMID:34715128)
• CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress. (PMID:37924725)
• The E3 ligase TRIM22 functions as a tumor suppressor in breast cancer by targeting CCS for proteasomal degradation to inhibit STAT3 signaling. (PMID:39127340)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccs	ENSDARG00000092003
danio_rerio	CCS	ENSDARG00000116246
mus_musculus	Ccs	ENSMUSG00000034108
rattus_norvegicus	Ccs	ENSRNOG00000047816
drosophila_melanogaster	Ccs	FBGN0010531

Paralogs (2): SOD3 (ENSG00000109610), SOD1 (ENSG00000142168)

Protein

Protein identifiers

Copper chaperone for superoxide dismutase — O14618 (reviewed: O14618)

Alternative names: Superoxide dismutase copper chaperone

All UniProt accessions (4): O14618, E9PK03, E9PP76, J3KNF4

UniProt curated annotations — full annotation on UniProt →

Function. Delivers copper to copper zinc superoxide dismutase (SOD1).

Subunit / interactions. Homodimer, and heterodimer with SOD1. Interacts with COMMD1. Interacts with XIAP/BIRC4. Interacts with SLC31A1(via C-terminal domain); this interaction is Cu(1+)-mediated. The heterodimer CCS:SOD1 interacts with SLC31A1; this heterotrimer is Cu(1+)-mediated and its maintenance is regulated through SOD1 activation.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous.

Post-translational modifications. Ubiquitinion by XIAP/BIRC4 leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. XIAP/BIRC4 preferentially ubiquitinates at Lys-241.

Cofactor. Binds 2 copper ions per subunit. Binds 1 zinc ion per subunit.

Similarity. In the C-terminal section; belongs to the Cu-Zn superoxide dismutase family.

RefSeq proteins (1): NP_005116* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001424	SOD_Cu_Zn_dom	Domain
IPR006121	HMA_dom	Domain
IPR018152	SOD_Cu/Zn_BS	Binding_site
IPR024134	SOD_Cu/Zn_/chaperone	Family
IPR036163	HMA_dom_sf	Homologous_superfamily
IPR036423	SOD-like_Cu/Zn_dom_sf	Homologous_superfamily

Pfam: PF00080, PF00403

UniProt features (46 total): strand 17, binding site 8, cross-link 4, mutagenesis site 4, helix 4, turn 2, chain 1, domain 1, modified residue 1, disulfide bond 1, sequence variant 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6FN8	X-RAY DIFFRACTION	1.55
6FOL	X-RAY DIFFRACTION	2.55
1DO5	X-RAY DIFFRACTION	2.75
6FP6	X-RAY DIFFRACTION	3
6FON	X-RAY DIFFRACTION	3.05
2CRL	SOLUTION NMR
2RSQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14618-F1	87.54	0.74

Functional residue map

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

Ligand- & substrate-binding residues (8): 246; 22; 25; 147; 155; 164; 167; 244

Post-translational modifications (5): 267, 76, 189, 216, 241

Disulfide bonds (1): 141–227

Mutagenesis-validated functional residues (4):

Position	Phenotype
22	reduces copper binding by half; when associated with s-25. negligible effect on zinc binding.
25	reduces copper binding by half; when associated with s-22. negligible effect on zinc binding.
244	reduces copper binding by half; when associated with s-246. negligible effect on zinc binding.
246	reduces copper binding by half; when associated with s-244. negligible effect on zinc binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-3299685	Detoxification of Reactive Oxygen Species
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress

MSigDB gene sets: 153 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_SUPEROXIDE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr11q13, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, GOBP_PROTEIN_MATURATION, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_DETOXIFICATION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_RADICAL, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE

GO Biological Process (4): removal of superoxide radicals (GO:0019430), cellular response to oxidative stress (GO:0034599), protein maturation (GO:0051604), superoxide metabolic process (GO:0006801)

GO Molecular Function (6): copper ion binding (GO:0005507), protein-disulfide reductase activity (GO:0015035), superoxide dismutase copper chaperone activity (GO:0016532), cadherin binding (GO:0045296), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular response to chemical stress	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
superoxide metabolic process	1
cellular response to superoxide	1
cellular oxidant detoxification	1
response to oxidative stress	1
cellular response to chemical stress	1
gene expression	1
protein metabolic process	1
reactive oxygen species metabolic process	1
transition metal ion binding	1
disulfide oxidoreductase activity	1
catalytic activity, acting on a protein	1
copper chaperone activity	1
cell adhesion molecule binding	1
binding	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCS	ATOX1	O00244	950
CCS	COX17	Q14061	811
CCS	SLC31A1	O15431	732
CCS	SLC31A2	O15432	714
CCS	ATP7A	Q04656	713
CCS	ATP7B	P35670	690
CCS	COX11	Q9Y6N1	649
CCS	SCO1	O75880	643
CCS	SOD1	P00441	630
CCS	CP	P00450	611
CCS	SCO2	O43819	591
CCS	CZIB	Q9NWV4	574
CCS	PRDX3	P30048	571
CCS	PRDX2	P31945	565
CCS	BACE1	P56817	559

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CCS	SOD1	psi-mi:“MI:0915”(physical association)	0.830
SOD1	CCS	psi-mi:“MI:0914”(association)	0.830
CCS	SOD1	psi-mi:“MI:0914”(association)	0.830
SOD1	CCS	psi-mi:“MI:0915”(physical association)	0.830
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
CCS	XIAP	psi-mi:“MI:0915”(physical association)	0.500
APBA2	CCS	psi-mi:“MI:0407”(direct interaction)	0.440
CZIB	CCS	psi-mi:“MI:0915”(physical association)	0.370
FCN1	CCS	psi-mi:“MI:0915”(physical association)	0.370
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.350
SCRN2	CCS	psi-mi:“MI:0914”(association)	0.350
DNAL4	WDR91	psi-mi:“MI:0914”(association)	0.350
APBA1	KIF2A	psi-mi:“MI:0914”(association)	0.350
ZFHX3	CCS	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (68): CCS (Affinity Capture-MS), CCS (Affinity Capture-MS), ATOX1 (Co-fractionation), CCS (Co-fractionation), CCS (Co-fractionation), CCS (Co-fractionation), CCS (Co-fractionation), PPIL3 (Co-fractionation), RAE1 (Co-fractionation), CCS (Affinity Capture-MS), CCS (Affinity Capture-MS), CCS (Affinity Capture-MS), CCS (Proximity Label-MS), CCS (Affinity Capture-MS), CCS (Affinity Capture-MS)

ESM2 similar proteins: A0JNU3, A5WVX1, A8XCP3, D3ZBP4, D3ZX08, F1MH07, J9VLJ9, O12933, O14618, O49044, O55137, O55171, O88202, O88267, P09958, P10688, P10895, P11418, P23188, P23377, P24706, P51178, P51687, P81926, P82205, Q05B89, Q14CH7, Q4V7D6, Q5JTZ9, Q60HD0, Q641W2, Q6NTR1, Q6PWT7, Q86U10, Q8MIR4, Q8R086, Q8R123, Q8R3B1, Q8VDP3, Q8WNN6

Diamond homologs: A0A1D1VU85, A2XGP6, C0HK70, H6BDU4, J9VLJ9, O04996, O04997, O12933, O14618, O22668, O46412, O49044, O49073, O65174, O65175, O65198, O65199, O65768, O73872, O78310, P00441, P00442, P00443, P04178, P07505, P07632, P08228, P09212, P09670, P09678, P10791, P10792, P11418, P11428, P11964, P13926, P14830, P14831, P15107, P22233

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1150 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66599184:G:GT	donor_gain	1.0000
11:66599249:GTTGC:G	donor_gain	1.0000
11:66599252:GC:G	donor_gain	1.0000
11:66600487:A:AG	acceptor_gain	1.0000
11:66600488:G:GG	acceptor_gain	1.0000
11:66600488:GCT:G	acceptor_gain	1.0000
11:66600488:GCTGT:G	acceptor_gain	1.0000
11:66600546:CCGGG:C	donor_loss	1.0000
11:66600547:CGGG:C	donor_loss	1.0000
11:66600548:GG:G	donor_gain	1.0000
11:66600548:GGGT:G	donor_loss	1.0000
11:66600549:GG:G	donor_gain	1.0000
11:66600549:GGT:G	donor_loss	1.0000
11:66600550:GTAAG:G	donor_loss	1.0000
11:66600551:T:TC	donor_loss	1.0000
11:66593373:G:GT	donor_gain	0.9900
11:66593373:G:T	donor_gain	0.9900
11:66599202:G:GT	donor_gain	0.9900
11:66599207:C:T	donor_gain	0.9900
11:66599220:G:GT	donor_gain	0.9900
11:66599232:GGCA:G	donor_gain	0.9900
11:66599250:T:G	donor_gain	0.9900
11:66599254:G:GG	donor_gain	0.9900
11:66599457:A:AG	acceptor_gain	0.9900
11:66599458:G:GG	acceptor_gain	0.9900
11:66599637:G:GA	donor_loss	0.9900
11:66599638:T:A	donor_loss	0.9900
11:66600483:TCTTA:T	acceptor_loss	0.9900
11:66600484:CTTAG:C	acceptor_loss	0.9900
11:66600485:TTAG:T	acceptor_loss	0.9900

AlphaMissense

1781 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66605508:G:C	R196P	0.995
11:66599600:T:A	V131D	0.994
11:66605510:A:C	S197R	0.993
11:66605512:C:A	S197R	0.993
11:66605512:C:G	S197R	0.993
11:66605786:G:C	W252C	0.993
11:66605786:G:T	W252C	0.993
11:66605719:T:A	I230N	0.992
11:66605753:G:C	K241N	0.991
11:66605753:G:T	K241N	0.991
11:66593648:T:C	F16L	0.990
11:66593650:C:A	F16L	0.990
11:66593650:C:G	F16L	0.990
11:66593649:T:C	F16S	0.989
11:66605505:G:A	G195D	0.987
11:66599155:T:A	V51D	0.986
11:66605767:G:A	C246Y	0.985
11:66599474:C:A	A89E	0.984
11:66605507:C:A	R196S	0.984
11:66605514:T:C	L198P	0.984
11:66599522:T:C	F105S	0.983
11:66599557:G:A	G117R	0.983
11:66599557:G:C	G117R	0.983
11:66599612:G:A	G135E	0.983
11:66599509:G:T	G101W	0.982
11:66605534:G:C	D205H	0.982
11:66605722:C:A	A231E	0.982
11:66605721:G:C	A231P	0.981
11:66605761:G:A	C244Y	0.981
11:66599479:G:C	A91P	0.980

dbSNP variants (sampled 300 via entrez): RS1000310726 (11:66596825 G>A,C), RS1000727023 (11:66594179 A>G), RS1001785724 (11:66601782 C>T), RS1001857744 (11:66603630 A>G), RS1001942552 (11:66594791 A>C,T), RS1002360571 (11:66597681 G>A), RS1002417971 (11:66604794 G>C), RS1002857887 (11:66592715 C>A,G,T), RS1002961501 (11:66599639 G>T), RS1003140973 (11:66592929 C>A), RS1003191553 (11:66593926 T>C), RS1003214037 (11:66596160 C>T), RS1003458577 (11:66603401 C>T), RS1003473448 (11:66594225 G>C), RS1004086211 (11:66600281 C>T)

Disease associations

OMIM: gene MIM:603864 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
disorder of copper metabolism	No Known Disease Relationship	UD

Mondo (1): neurodegenerative disease (MONDO:0005559)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001241_12	Bipolar disorder	2.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D019636	Neurodegenerative Diseases	C10.574

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Copper	affects localization, affects transport, affects binding, increases activity, increases reaction (+1 more)	8
Copper Sulfate	affects cotreatment, increases expression, decreases reaction, decreases expression	3
Valproic Acid	decreases methylation, affects expression	2
Cadmium Chloride	increases abundance, increases expression	2
testosterone enanthate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
hesperetin	affects binding	1
beta-lapachone	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	affects reaction, increases expression	1
tetrathiomolybdate	decreases expression	1
2,3,2-tetramine	increases expression, decreases reaction	1
cerous chloride	affects cotreatment, affects expression, decreases expression	1
lanthanum chloride	affects cotreatment, affects expression	1
cupric chloride	decreases expression, increases degradation	1
tetraethylenepentamine	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
cuprous sulfide	decreases expression	1
2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole	increases expression	1
obeticholic acid	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 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	increases expression	1
Oxaliplatin	affects response to substance, increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1LY	Abcam K-562 CCS KO	Cancer cell line	Female
CVCL_D2II	Abcam Raji CCS KO	Cancer cell line	Male
CVCL_UQ30	Abcam Jurkat CCS KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT05357612	PHASE4	RECRUITING	Characterization of the Serotonin 2A Receptor Selective PET Tracer [18F]MH.MZ in Patients With Neurodegenerative Diseases
NCT05508789	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Donanemab (LY3002813) in Participants With Early Symptomatic Alzheimer’s Disease (TRAILBLAZER-ALZ 5)
NCT05738486	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Different Donanemab (LY3002813) Dosing Regimens in Adults With Early Alzheimer’s Disease (TRAILBLAZER-ALZ 6)
NCT06111014	PHASE3	TERMINATED	Continuation Study for Latozinemab
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT00001365	PHASE2	COMPLETED	Dextromethorphan for the Treatment of Parkinson’s Disease and Similar Conditions of the Nervous System
NCT00406029	PHASE2	COMPLETED	Dyskinesia in Parkinson’s Disease (Study P04501)
NCT00537017	PHASE2	COMPLETED	Follow Up Safety Study of SCH 420814 in Subjects With Parkinson’s Disease (P05175)
NCT00907283	PHASE2	UNKNOWN	Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA)
NCT01518374	PHASE2	COMPLETED	Clinical Evaluation of Florbetapir F 18 (18F-AV-45)
NCT02656498	PHASE2	COMPLETED	[18F]THK-5351 Positron Emission Computed Tomography Study of Normal, Mild Cognitive Impairment, Alzheimer’s Disease and Other Neurodegenerative Disease
NCT03127514	PHASE2	COMPLETED	AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT03538522	PHASE2	COMPLETED	A Double-Blind, Placebo-Controlled Safety and Efficacy Study of NA-831
NCT04838301	PHASE2	RECRUITING	Allopregnanolone Regenerative Therapeutic for Mild Alzheimer’s Disease
NCT04937452	PHASE2	COMPLETED	Dopaminergic Therapy for Frontotemporal Dementia Patients
NCT05318976	PHASE2	COMPLETED	A Study of XPro1595 in Patients With Early Alzheimer’s Disease With Biomarkers of Inflammation
NCT05321498	PHASE2	WITHDRAWN	Study to Assess the Efficacy of XPro1595 in Patients With Mild Cognitive Impairment With Biomarkers of Inflammation
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT05522387	PHASE2	TERMINATED	An Open-Label Extension of XPro1595 in Patients With Alzheimer’s Disease
NCT00316797	PHASE1	COMPLETED	Biodistribution and Safety of a Radiopharmaceutical in Healthy Subjects
NCT01758510	PHASE1	COMPLETED	Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis
NCT02267434	PHASE1	COMPLETED	Study Assessing Tolerability and Safety of AFFITOPE® PD03A in Patients With Early Parkinson’s Disease
NCT02270489	PHASE1	COMPLETED	Study Assessing Safety and Therapeutic Activity of AFFITOPE® PD01A and PD03A in Patients With Early MSA
NCT03065192	PHASE1	COMPLETED	Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson’s Disease
NCT04578028	PHASE1	COMPLETED	A First in Human Study to Assess the Safety, Tolerability and Pharmacokinetics of ONO-2808-01 in Healthy Participants
NCT05143463	PHASE1	COMPLETED	A FIH Study to Assess the Safety and Tolerability of NS Intravenous NS101 Infusion
NCT05490576	PHASE1	UNKNOWN	Tau And Connectomics In TES Study
NCT05792163	PHASE1	COMPLETED	A First Time in Human Study of SNP318 as a Treatment for Neurodegenerative Diseases Including Alzheimer’s Disease
NCT07232147	PHASE1	NOT_YET_RECRUITING	Clinical Research on Stem Cell Therapy for Parkinson’s Disease
NCT03143374	PHASE2/PHASE3	RECRUITING	PET Tau - Neurodegenerative Disease Imaging
NCT06122662	PHASE2/PHASE3	COMPLETED	AMX0035 and Progressive Supranuclear Palsy
NCT03295786	PHASE1/PHASE2	COMPLETED	Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson’s Disease
NCT05853471	PHASE1/PHASE2	UNKNOWN	[18F]MC225-PET in Neurodegenerative Disease
NCT06447194	PHASE1/PHASE2	WITHDRAWN	Effect of RECK in Posterior Spinal Fusion
NCT06934720	PHASE1/PHASE2	NOT_YET_RECRUITING	VR-based Physical Activity and Reminiscence Therapy
NCT02452216	EARLY_PHASE1	COMPLETED	Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS
NCT04575727	EARLY_PHASE1	COMPLETED	Exploratory Evaluation of [11C]MPC6827
NCT06181513	EARLY_PHASE1	RECRUITING	Probiotics in Mild Alzheimer’s Disease