CCS

copper chaperone for superoxide dismutase

Basic information

Region (hg38): 11:66593153-66606019

Links

ENSG00000173992 ∙ NCBI:9973 ∙ OMIM:603864 ∙ HGNC:1613 ∙ Uniprot:O14618 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCS gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			19			19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding						0
Total	0	0	20	1	1

Variants in CCS

This is a list of pathogenic ClinVar variants found in the CCS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-66593691-G-A		not specified	Uncertain significance (Dec 08, 2023)
11-66593709-T-G		not specified	Uncertain significance (May 24, 2024)
11-66599209-C-T		not specified	Uncertain significance (Sep 26, 2023)
11-66599214-C-T		not specified	Uncertain significance (Jan 10, 2022)
11-66599487-G-T		CCS-related disorder	Likely benign (Mar 02, 2020)
11-66599515-G-C		not specified	Uncertain significance (Dec 07, 2022)
11-66599557-G-A		not specified	Uncertain significance (Jun 24, 2022)
11-66599618-T-C		not specified	Uncertain significance (Feb 15, 2023)
11-66600509-C-T		not specified	Uncertain significance (Apr 22, 2022)
11-66600547-C-T		Neurodegeneration	Uncertain significance (Aug 01, 2012)
11-66600548-G-T		not specified	Uncertain significance (Sep 20, 2023)
11-66605384-G-A		not specified	Uncertain significance (Aug 09, 2021)
11-66605406-A-G		not specified	Uncertain significance (Dec 22, 2023)
11-66605417-G-C			Uncertain significance (Dec 03, 2020)
11-66605547-G-A		not specified	Uncertain significance (May 23, 2023)
11-66605563-A-C		not specified	Uncertain significance (Aug 22, 2023)
11-66605713-G-C		not specified	Uncertain significance (Mar 28, 2023)
11-66605730-G-A		not specified	Uncertain significance (Dec 19, 2023)
11-66605746-A-G		not specified	Uncertain significance (Aug 21, 2023)
11-66605805-A-G		not specified	Uncertain significance (Apr 18, 2024)
11-66605808-G-A		not specified	Uncertain significance (Oct 29, 2021)
11-66605808-G-T		not specified	Uncertain significance (Sep 14, 2023)
11-66605818-G-C		not specified	Uncertain significance (Jul 14, 2021)
11-66605834-G-A		CCS-related disorder	Benign (Nov 12, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCS	protein_coding	protein_coding	ENST00000533244	8	13199

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.63e-8	0.305	125668	0	80	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.400	156	171	0.914	0.0000107	1756
Missense in Polyphen		54	58.298	0.92628		563
Synonymous	1.16	56	68.2	0.821	0.00000442	557
Loss of Function	0.528	12	14.1	0.848	7.67e-7	149

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000528	0.000526
Ashkenazi Jewish	0.000235	0.000198
East Asian	0.000329	0.000326
Finnish	0.0000953	0.0000924
European (Non-Finnish)	0.000417	0.000413
Middle Eastern	0.000329	0.000326
South Asian	0.000218	0.000196
Other	0.000666	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Delivers copper to copper zinc superoxide dismutase (SOD1).
• Pathway: Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS);Copper homeostasis;Detoxification of Reactive Oxygen Species;Cellular responses to stress;Cellular responses to external stimuli (Consensus)

Recessive Scores

• pRec: 0.326

Intolerance Scores

• loftool: 0.339
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.32

Haploinsufficiency Scores

• pHI: 0.0676
• hipred: N
• hipred_score: 0.368
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.847

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ccs
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; reproductive system phenotype

Gene ontology

• Biological process: superoxide metabolic process;protein maturation by copper ion transfer;removal of superoxide radicals;metal ion transport;cellular response to oxidative stress;positive regulation of oxidoreductase activity;oxidation-reduction process
• Cellular component: extracellular space;nucleus;cytoplasm;cytosol
• Molecular function: superoxide dismutase activity;copper ion binding;protein binding;zinc ion binding;protein disulfide oxidoreductase activity;superoxide dismutase copper chaperone activity;cadherin binding