PCBD1

pterin-4 alpha-carbinolamine dehydratase 1

Basic information

Region (hg38): 10:70882279-70888565

Previous symbols: [ "DCOH", "PCBD" ]

Links

ENSG00000166228 ∙ NCBI:5092 ∙ OMIM:126090 ∙ HGNC:8646 ∙ Uniprot:P61457 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pterin-4 alpha-carbinolamine dehydratase 1 deficiency (Definitive), mode of inheritance: AR
• pterin-4 alpha-carbinolamine dehydratase 1 deficiency (Strong), mode of inheritance: AR
• pterin-4 alpha-carbinolamine dehydratase 1 deficiency (Moderate), mode of inheritance: AR
• pterin-4 alpha-carbinolamine dehydratase 1 deficiency (Strong), mode of inheritance: AR
• pterin-4 alpha-carbinolamine dehydratase 1 deficiency (Supportive), mode of inheritance: AR
• pterin-4 alpha-carbinolamine dehydratase 1 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperphenylalaninemia, BH4-deficient, D	AR	Renal	In addition to other findings, patients may develop hypomagnesemia with renal magnesium loss, and awareness may allow medical management (magnesium supplementation), which has been reported as clinically beneficial	Biochemical; Endocrine; Renal	8352282; 9585615; 9760199; 24204001; 24848070
Individuals have been treated with phenylalanine restriction and BH4 supplementation, but such interventions may not be indicated

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCBD1 gene.

• Pterin-4 alpha-carbinolamine dehydratase 1 deficiency (63 variants)
• not provided (16 variants)
• Inborn genetic diseases (2 variants)
• BH4-Deficient Hyperphenylalaninemia (1 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCBD1 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				15		15
missense		2	12	1		15
nonsense		2				2
start loss						0
frameshift	4	2				6
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3		3
non coding			7	17	9	33
Total	4	6	19	33	9

Highest pathogenic variant AF is 0.0000131

Variants in PCBD1

This is a list of pathogenic ClinVar variants found in the PCBD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-70883544-AAC-A		BH4-Deficient Hyperphenylalaninemia	Uncertain significance (Jun 14, 2016)
10-70883697-A-T		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Benign/Likely benign (Mar 29, 2019)
10-70883834-G-A		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Uncertain significance (Jan 12, 2018)
10-70883836-C-T		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Likely benign (Jan 13, 2018)
10-70883843-G-A		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Uncertain significance (Jan 12, 2018)
10-70883914-C-T		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Benign (Sep 05, 2021)
10-70883921-C-T		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Uncertain significance (Jan 13, 2018)
10-70883952-A-G		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Conflicting classifications of pathogenicity (Jul 05, 2022)
10-70883957-A-T		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Uncertain significance (Feb 19, 2022)
10-70883965-T-G		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Likely benign (Dec 22, 2023)
10-70883971-T-C		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Conflicting classifications of pathogenicity (Jan 19, 2024)
10-70883973-G-A		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Pathogenic/Likely pathogenic (Jan 18, 2024)
10-70883976-C-T		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Likely pathogenic (Dec 23, 2023)
10-70883977-G-A		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Likely benign (May 31, 2023)
10-70883979-T-C		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Uncertain significance (Oct 03, 2022)
10-70883984-C-A		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Uncertain significance (Sep 01, 2021)
10-70883992-GT-G		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Pathogenic (May 28, 2019)
10-70883995-T-G		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Likely benign (Jan 18, 2024)
10-70884001-C-G		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Likely benign (Dec 27, 2023)
10-70884002-C-T		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency • Inborn genetic diseases • PCBD1-related disorder	Likely benign (Jan 30, 2024)
10-70884003-G-A		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Uncertain significance (Jun 13, 2022)
10-70884003-G-T		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Likely benign (May 22, 2023)
10-70884006-C-A		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Pathogenic/Likely pathogenic (Jan 08, 2024)
10-70884011-AGG-CACCCATGGTGAGCAC			Likely pathogenic (Sep 01, 2022)
10-70884013-G-A		Pterin-4 alpha-carbinolamine dehydratase 1 deficiency	Likely benign (Jun 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCBD1	protein_coding	protein_coding	ENST00000299299	4	6505

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000332	0.383	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.716	42	57.2	0.734	0.00000338	693
Missense in Polyphen		16	22.696	0.70497		265
Synonymous	-0.486	27	24.0	1.13	0.00000150	189
Loss of Function	-0.107	5	4.75	1.05	2.07e-7	62

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity.
• Disease: DISEASE: Hyperphenylalaninemia, BH4-deficient, D (HPABH4D) [MIM:264070]: An autosomal recessive disease characterized by primapterinuria, a variant form of hyperphenylalaninemia defined by increased excretion of 7-substituted pterins in the urine. Patients with primapterinuria show an increased ratio of neopterin to biopterin in the urine, excretion of subnormal levels of biopterins, and normal levels of biogenic amines in cerebrospinal fluid. Neurologic signs are mild, present in the neonatal period only, and include hypotonia, delayed motor development and tremor. {ECO:0000269|PubMed:8352282, ECO:0000269|PubMed:9760199}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Folate biosynthesis - Homo sapiens (human);phenylalanine degradation/tyrosine biosynthesis;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Phenylalanine and tyrosine catabolism;Biopterin metabolism;Metabolism (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.574
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.300
• hipred: Y
• hipred_score: 0.553
• ghis: 0.569

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pcbd1
• Phenotype: renal/urinary system phenotype; vision/eye phenotype; pigmentation phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: L-phenylalanine catabolic process;tetrahydrobiopterin biosynthetic process;regulation of protein homodimerization activity;positive regulation of transcription, DNA-templated;protein homotetramerization;protein heterooligomerization;oxidation-reduction process
• Cellular component: nucleus;nucleoplasm;cytosol;extracellular exosome
• Molecular function: transcription coactivator activity;phenylalanine 4-monooxygenase activity;protein binding;4-alpha-hydroxytetrahydrobiopterin dehydratase activity;identical protein binding