CP

ceruloplasmin

Basic information

Region (hg38): 3:149162409-149221829

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

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 (421 variants)
• not provided (162 variants)
• Inborn genetic diseases (40 variants)
• not specified (36 variants)
• Hermansky-Pudlak syndrome 3 (16 variants)
• Hermansky-Pudlak syndrome (5 variants)
• CP-related condition (3 variants)
• Neurodegeneration with brain iron accumulation (2 variants)
• Hypoceruloplasminemia (2 variants)
• Hemosiderosis, systemic, due to aceruloplasminemia (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.

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			4	78	4	86
missense		5	208	14	3	230
nonsense	10	1				11
start loss			1			1
frameshift	8	4				12
inframe indel			4			4
splice donor/acceptor (+/-2bp)	4	2	1			7
splice region			12	13	3	28
non coding			14	57	72	143
Total	22	12	232	149	79

Highest pathogenic variant AF is 0.0000329

Variants in CP

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

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

Position	Type	Phenotype	Significance	ClinVar
3-149162442-CAG-C			Benign (Jul 09, 2018)
3-149162672-C-T			Likely benign (Jul 12, 2023)
3-149162679-C-T			Likely benign (Jun 14, 2023)
3-149162681-G-C			Likely benign (Jul 13, 2023)
3-149162681-GTTTTTAAGGTGC-G			Likely pathogenic (Oct 20, 2022)
3-149162689-G-A			Likely pathogenic (Sep 08, 2021)
3-149162710-A-G			Likely benign (May 23, 2021)
3-149162712-A-G		Inborn genetic diseases	Uncertain significance (Dec 30, 2023)
3-149162713-T-C			Likely benign (Dec 01, 2018)
3-149162714-AC-A			Pathogenic (Apr 11, 2023)
3-149162719-T-A			Likely benign (Dec 18, 2023)
3-149162730-T-C		Inborn genetic diseases	Uncertain significance (Apr 09, 2022)
3-149162734-A-G			Likely benign (Jun 16, 2023)
3-149162737-CTT-C		Hermansky-Pudlak syndrome 3	Pathogenic/Likely pathogenic (Jan 18, 2024)
3-149162739-T-C			Uncertain significance (Mar 26, 2021)
3-149162752-G-A			Likely benign (Jan 22, 2024)
3-149162758-G-A			Likely benign (Sep 10, 2021)
3-149162761-A-G		Hermansky-Pudlak syndrome	Likely benign (Jan 22, 2024)
3-149162767-C-G		Hermansky-Pudlak syndrome	Likely benign (Sep 05, 2023)
3-149162775-T-C		Hermansky-Pudlak syndrome 3 • Hermansky-Pudlak syndrome • HPS3-related disorder	Conflicting classifications of pathogenicity (Jan 28, 2024)
3-149162775-TG-T		Hermansky-Pudlak syndrome 3	Likely pathogenic (Mar 30, 2022)
3-149162776-G-T			Likely benign (Jun 20, 2020)
3-149162784-A-G			Uncertain significance (Oct 21, 2020)
3-149162788-A-G			Likely benign (Oct 13, 2023)
3-149162791-C-G			Likely benign (Jun 05, 2023)

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