CP

ceruloplasmin

Basic information

Region (hg38): 3:149162410-149221829

Links

ENSG00000047457

∙ NCBI:1356 ∙ OMIM:117700 ∙ HGNC:2295 ∙ Uniprot:P00450 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

aceruloplasminemia (Strong), mode of inheritance: AR
aceruloplasminemia (Definitive), mode of inheritance: AR
aceruloplasminemia (Supportive), mode of inheritance: AR
aceruloplasminemia (Strong), mode of inheritance: AR
disorder of iron metabolism and transport (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aceruloplasminemia	AR	Biochemical	In Aceruloplasminemia, medical management can be beneficial (eg, with iron chelating agents to decrease serum ferritin, brain and liver iron stores, and prevent progression of neurologic signs/symptoms; Combined IV desferrioxamine and fresh-frozen plasma can decrease liver iron content; repetitive FFP treatment can improve neurologic manifestations; antioxidants and oral zinc and deferasirox may prevent tissue damage to the liver and pancreas	Biochemical; Endocrine; Gastrointestinal; Neurologic; Ophthalmologic	3574673; 1458725; 7820540; 7539672; 9066364; 20301666

ClinVar

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

Deficiency_of_ferroxidase (476 variants)
not_provided (139 variants)
Inborn_genetic_diseases (130 variants)
not_specified (32 variants)
CP-related_disorder (31 variants)
Neurodegeneration_with_brain_iron_accumulation (7 variants)
Hypoceruloplasminemia (1 variants)
Hermansky-Pudlak_syndrome (1 variants)
. (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000096.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	111 clinvar	4 clinvar	123
missense	9 clinvar	10 clinvar	279 clinvar	28 clinvar	1 clinvar	327
nonsense	16 clinvar	5 clinvar				21
start loss		1	1			2
frameshift	26 clinvar	7 clinvar	1 clinvar			34
splice donor/acceptor (+/-2bp)	14 clinvar	6 clinvar	1 clinvar			21
Total	65	29	290	139	5

Highest pathogenic variant AF is 0.00009665248

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CP	protein_coding	protein_coding	ENST00000264613	19	59646

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.20e-10	1.00	114812	0	10936	125748	0.0445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.223	550	565	0.974	0.0000281	7076
Missense in Polyphen		152	195.24	0.77853		2418
Synonymous	-1.09	221	201	1.10	0.0000109	1926
Loss of Function	3.66	25	54.1	0.462	0.00000262	689

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0682	0.0685
Ashkenazi Jewish	0.0373	0.0368
East Asian	0.0349	0.0351
Finnish	0.0397	0.0395
European (Non-Finnish)	0.0553	0.0556
Middle Eastern	0.0349	0.0351
South Asian	0.0326	0.0325
Other	0.0490	0.0493

dbNSFP

Source: dbNSFP

Function: FUNCTION: Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. May also play a role in fetal lung development or pulmonary antioxidant defense (By similarity). {ECO:0000250}.;
Disease: DISEASE: Note=Ceruloplasmin levels are decreased in Wilson disease, in which copper cannot be incorporated into ceruloplasmin in liver because of defects in the copper-transporting ATPase 2.;
Pathway: Porphyrin and chlorophyll metabolism - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Methionine and cysteine metabolism;Metal ion SLC transporters;Iron uptake and transport;HIF-1-alpha transcription factor network (Consensus)

Recessive Scores

pRec: 0.673

Intolerance Scores

loftool: 0.0942
rvis_EVS: 0.25
rvis_percentile_EVS: 69.7

Haploinsufficiency Scores

pHI: 0.433
hipred: Y
hipred_score: 0.652
ghis: 0.407

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cp
Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: cp
Affected structure: otolith
Phenotype tag: abnormal
Phenotype quality: morphology

Gene ontology

Biological process: copper ion transport;iron ion transport;cellular iron ion homeostasis;post-translational protein modification;cellular protein metabolic process;iron ion homeostasis;oxidation-reduction process
Cellular component: extracellular region;extracellular space;lysosomal membrane;endoplasmic reticulum lumen;plasma membrane;extracellular exosome;blood microparticle
Molecular function: ferroxidase activity;copper ion binding;oxidoreductase activity;chaperone binding