| Disease | OMIM/Classification | Inheritance | Mechanism | Key Features | References |
|---|---|---|---|---|---|
| Transient neonatal hyperphenylalaninemia and primapterinuria / pterin-4α-carbinolamine dehydratase deficiency | OMIM #264070; BH4 recycling disorder | Autosomal recessive | Loss of PCBD1 dehydratase activity impairs conversion of BH4-4a-carbinolamine to quinonoid dihydrobiopterin, reducing BH4 recycling in phenylalanine hydroxylation | Mild/transient or benign neonatal hyperphenylalaninemia, elevated urinary 7-biopterin (primapterinuria); excellent prognosis in many cases; ~30 patients and 32 variants documented as of 2023 | (pqac-00000022, pqac-00000035, pqac-00000020, pqac-00000041) |
| Hypomagnesemia with renal magnesium wasting | Renal tubulopathy associated with PCBD1 deficiency | Autosomal recessive | Impaired nuclear co-activation of HNF1B by PCBD1 reduces transcription of FXYD2 in the distal convoluted tubule, disrupting renal Mg2+ reabsorption | Hypomagnesemia, inappropriate renal Mg2+ loss/wasting, distal convoluted tubule involvement; may emerge later than neonatal HPA phenotype | (pqac-00000019, pqac-00000020, pqac-00000021, pqac-00000034) |
| MODY-like diabetes / early-onset non-autoimmune diabetes | MODY-like phenotype with HNF1A/HNF1B-like features | Usually associated with biallelic PCBD1 loss-of-function in reported families | Impaired PCBD1 cofactor function destabilizes or weakens HNF1A/HNF1B transcriptional activity, affecting pancreatic development and/or β-cell function | Early-onset non-autoimmune diabetes, clinical overlap with MODY3/MODY5; may coexist with hypomagnesemia; some reviews note possible response to sulphonylureas or glinides | (pqac-00000019, pqac-00000036, pqac-00000037, pqac-00000038, pqac-00000040) |
| Type 2 diabetes mellitus association | OpenTargets disease association; also discussed in recent MODY/diabetes reviews | Not established as a Mendelian PCBD1 disorder in this context | Likely reflects PCBD1’s role in HNF1-related transcriptional regulation and/or low-penetrance contribution to diabetes susceptibility rather than classic BH4 deficiency alone | OpenTargets target-disease association score ~0.46 for type 2 diabetes mellitus; heterozygous variants have been proposed as possible contributors in some contexts | (pqac-00000000, pqac-00000037, pqac-00000038) |
| Atherosclerosis / abdominal aortic aneurysm transcriptomic association | Exploratory biomarker/transcriptomic association, not an established monogenic PCBD1 disease | Not established | 2024 transcriptomic analysis identified reduced PCBD1 expression among fatty-acid-metabolism-related signature genes shared between atherosclerosis and abdominal aortic aneurysm | Proposed diagnostic biomarker context only; evidence is associative and does not establish causality for PCBD1 | (pqac-00000000) |


*Table: This table summarizes the main disease phenotypes and emerging disease associations linked to human PCBD1/DCoH, separating well-established Mendelian disorders from more preliminary association-based findings. It is useful for connecting PCBD1’s dual enzymatic and transcriptional cofactor functions to clinical outcomes.*