CPOX

coproporphyrinogen oxidase

Basic information

Region (hg38): 3:98579445-98593648

Previous symbols: [ "CPO" ]

Links

ENSG00000080819 ∙ NCBI:1371 ∙ OMIM:612732 ∙ HGNC:2321 ∙ Uniprot:P36551 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary coproporphyria (Strong), mode of inheritance: AD
• hereditary coproporphyria (Strong), mode of inheritance: AR
• hereditary coproporphyria (Strong), mode of inheritance: AD
• harderoporphyria (Strong), mode of inheritance: AR
• hereditary coproporphyria (Strong), mode of inheritance: AR
• hereditary coproporphyria (Supportive), mode of inheritance: AD
• CPOX-related hereditary coproporphyria (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Coproporphyria; Harderoporphyria	AD/AR	Hematologic; Pharmacogenomic	In Coprophyria, attacks may be precipitated by a variety of agents (eg, fasting, as well as specific pharmaceutical agents, including oral contraceptives), which should be avoided; IV therapy (with heme arginate) has been described as effective; In heterozygotes, specific considerations are important in surgery (eg, use of IV glucose perioperatively) and related to agent selection for anesthesia induction; Liver transplanation has been described; In Harderoporphyria, individuals may suffer from neonatal hemolytic anemia, which may necessitate RBC transfusions	Gastrointestinal; Hematologic; Neurologic	14378650; 5838412; 4163920; 4393048; 74745; 6886003; 6502649; 6143037; 8012360; 8286403; 7757079; 11309681; 12227458; 12181641; 16151909; 16159891; 21103937; 23236641

ClinVar

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

• not provided (161 variants)
• Hereditary coproporphyria (85 variants)
• Inborn genetic diseases (17 variants)
• CPOX-related condition (6 variants)
• not specified (2 variants)
• Coproporphyria (2 variants)
• Harderoporphyria (2 variants)
• Harderoporphyria;Hereditary coproporphyria (2 variants)
• Hereditary coproporphyria;Harderoporphyria (1 variants)
• Acute intermittent porphyria (1 variants)
• CPOX-related disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPOX 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			5	25	6	36
missense		2	84	4	8	98
nonsense	3	1				4
start loss						0
frameshift	9	1				10
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			4	3		7
non coding			24	7	31	62
Total	13	6	116	36	45

Highest pathogenic variant AF is 0.0000132

Variants in CPOX

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

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

Position	Type	Phenotype	Significance	ClinVar
3-98579509-C-T		Hereditary coproporphyria	Uncertain significance (Jan 13, 2018)
3-98579530-C-G		Hereditary coproporphyria	Uncertain significance (Jan 12, 2018)
3-98579578-T-C		Hereditary coproporphyria	Benign (Jan 13, 2018)
3-98579607-C-T		Hereditary coproporphyria	Uncertain significance (Jan 12, 2018)
3-98579611-G-A		Hereditary coproporphyria	Benign (Jan 13, 2018)
3-98579637-T-C		Hereditary coproporphyria	Uncertain significance (Jan 13, 2018)
3-98579744-T-C		Hereditary coproporphyria	Uncertain significance (Jan 13, 2018)
3-98579756-C-T		Hereditary coproporphyria	Benign (Jan 13, 2018)
3-98579938-T-C		Hereditary coproporphyria	Uncertain significance (Jan 13, 2018)
3-98579971-A-G		Hereditary coproporphyria	Uncertain significance (Jan 12, 2018)
3-98580004-C-T		Hereditary coproporphyria	Benign (Jan 12, 2018)
3-98580050-T-G		Hereditary coproporphyria	Uncertain significance (Jan 12, 2018)
3-98580088-G-T		Hereditary coproporphyria	Benign (Jan 13, 2018)
3-98580104-T-TTAAGAA		Hereditary coproporphyria	Benign (Jun 14, 2016)
3-98580167-T-G		Hereditary coproporphyria	Uncertain significance (Jan 12, 2018)
3-98580177-G-A		Hereditary coproporphyria	Uncertain significance (Jan 13, 2018)
3-98580184-A-ATG		Hereditary coproporphyria	Uncertain significance (Jun 14, 2016)
3-98580208-A-T		Hereditary coproporphyria	Benign (Jan 12, 2018)
3-98580302-G-A		Hereditary coproporphyria	Benign (Jan 12, 2018)
3-98580332-T-C		Hereditary coproporphyria	Uncertain significance (Apr 27, 2017)
3-98580343-T-C		Hereditary coproporphyria	Uncertain significance (Jan 12, 2018)
3-98580354-C-G		Hereditary coproporphyria	Benign (Jan 13, 2018)
3-98580456-C-T		Hereditary coproporphyria	Benign (Jan 13, 2018)
3-98580488-A-G		Hereditary coproporphyria	Benign (Jan 13, 2018)
3-98580489-C-A		Hereditary coproporphyria	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPOX	protein_coding	protein_coding	ENST00000264193	7	72592

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.172	0.828	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	173	231	0.750	0.0000119	2901
Missense in Polyphen		61	109.86	0.55527		1292
Synonymous	-0.582	95	88.0	1.08	0.00000437	913
Loss of Function	3.03	5	19.4	0.258	9.11e-7	233

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the heme biosynthesis. Catalyzes the aerobic oxidative decarboxylation of propionate groups of rings A and B of coproporphyrinogen-III to yield the vinyl groups in protoporphyrinogen-IX.
• Disease: DISEASE: Hereditary coproporphyria (HCP) [MIM:121300]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Hereditary coproporphyria is an acute hepatic porphyria characterized by skin photosensitivity, attacks of abdominal pain, neurological disturbances, and psychiatric symptoms. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. Hereditary coproporphyria is biochemically characterized by overexcretion of coproporphyrin III in the urine and in the feces. {ECO:0000269|PubMed:12181641, ECO:0000269|PubMed:15896662, ECO:0000269|PubMed:16398658, ECO:0000269|PubMed:7757079, ECO:0000269|PubMed:7849704, ECO:0000269|PubMed:8012360, ECO:0000269|PubMed:8990017, ECO:0000269|PubMed:9048920, ECO:0000269|PubMed:9298818, ECO:0000269|PubMed:9888388}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Porphyrin and chlorophyll metabolism - Homo sapiens (human);Hereditary Coproporphyria (HCP);Porphyria Variegata (PV);Congenital Erythropoietic Porphyria (CEP) or Gunther Disease;Acute Intermittent Porphyria;Porphyrin Metabolism;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Heme Biosynthesis;hemoglobins chaperone;Heme biosynthesis;Metabolism of porphyrins;Metabolism;Porphyrin metabolism;Porphyrin metabolism;heme biosynthesis from uroporphyrinogen-III I;heme biosynthesis (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.146
• rvis_EVS: 0.42
• rvis_percentile_EVS: 76.96

Haploinsufficiency Scores

• pHI: 0.543
• hipred: N
• hipred_score: 0.475
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.138

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cpox
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; vision/eye 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); limbs/digits/tail phenotype; immune system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; craniofacial phenotype

Gene ontology

• Biological process: heme biosynthetic process;protoporphyrinogen IX biosynthetic process from glutamate;oxidation-reduction process
• Cellular component: cytoplasm;mitochondrion;mitochondrial intermembrane space;cytosol
• Molecular function: coproporphyrinogen oxidase activity;protein homodimerization activity