PCBD2

Summary

PCBD2 (pterin-4 alpha-carbinolamine dehydratase 2, HGNC:24474) is a protein-coding gene on chromosome 5q31.1, encoding Pterin-4-alpha-carbinolamine dehydratase 2 (Q9H0N5). Involved in tetrahydrobiopterin biosynthesis.

Predicted to enable 4-alpha-hydroxytetrahydrobiopterin dehydratase activity. Involved in positive regulation of DNA-templated transcription. Located in mitochondrion.

Source: NCBI Gene 84105 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_032151

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24474
Approved symbol	PCBD2
Name	pterin-4 alpha-carbinolamine dehydratase 2
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	DCOHM, DCOH2
Ensembl gene	ENSG00000132570
Ensembl biotype	protein_coding
OMIM	609836
Entrez	84105

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000254908, ENST00000504352, ENST00000510013, ENST00000512783, ENST00000938208, ENST00000938209, ENST00000938210

RefSeq mRNA: 1 — MANE Select: NM_032151 NM_032151

CCDS: CCDS43364

Canonical transcript exons

ENST00000254908 — 4 exons

Exon	Start	End
ENSE00000815295	134959040	134959120
ENSE00002071494	134905131	134905223
ENSE00002087401	134960586	134962644
ENSE00003547394	134910335	134910466

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 91.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5863 / max 97.8856, expressed in 1791 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58621	6.8522	1759
58622	3.2377	1474
58620	0.4963	272

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	91.57	silver quality
deltoid	UBERON:0001476	91.08	gold quality
vastus lateralis	UBERON:0001379	90.61	gold quality
quadriceps femoris	UBERON:0001377	90.58	gold quality
muscle of leg	UBERON:0001383	90.03	gold quality
gastrocnemius	UBERON:0001388	89.96	gold quality
skeletal muscle tissue	UBERON:0001134	89.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.26	gold quality
biceps brachii	UBERON:0001507	89.05	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.73	gold quality
muscle tissue	UBERON:0002385	88.49	gold quality
endothelial cell	CL:0000115	86.89	silver quality
epithelial cell of pancreas	CL:0000083	85.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.08	gold quality
heart left ventricle	UBERON:0002084	84.64	gold quality
cardiac ventricle	UBERON:0002082	84.40	gold quality
myocardium	UBERON:0002349	84.33	gold quality
body of pancreas	UBERON:0001150	83.79	gold quality
right lobe of liver	UBERON:0001114	83.22	gold quality
ventricular zone	UBERON:0003053	83.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.19	gold quality
right uterine tube	UBERON:0001302	83.11	gold quality
adrenal tissue	UBERON:0018303	82.85	gold quality
pancreatic ductal cell	CL:0002079	82.82	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.55	gold quality
heart	UBERON:0000948	82.38	gold quality
apex of heart	UBERON:0002098	82.01	gold quality
minor salivary gland	UBERON:0001830	81.92	gold quality
monocyte	CL:0000576	81.90	gold quality
ileal mucosa	UBERON:0000331	81.82	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, MYC

miRNA regulators (miRDB)

94 targeting PCBD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-1283	99.69	72.42	3009

Literature-anchored findings (GeneRIF, showing 2)

• PMID: 12646162 concludes Alu repeats interfere with splicing of DCOHM and CAVL such that transcripts containing exons of both genes exist. (PMID:12646162)
• MiR-3174 functions as an oncogene in rectal cancer by targeting PCBD2. (PMID:30964167)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pcbd2	ENSMUSG00000021496
rattus_norvegicus		ENSRNOG00000084656
drosophila_melanogaster	Pcd	FBGN0024841
caenorhabditis_elegans	pcbd-1	WBGENE00020397

Paralogs (1): PCBD1 (ENSG00000166228)

Protein

Protein identifiers

Pterin-4-alpha-carbinolamine dehydratase 2 — Q9H0N5 (reviewed: Q9H0N5)

Alternative names: 4-alpha-hydroxy-tetrahydropterin dehydratase 2, DcoH-like protein DCoHm, Dimerization cofactor of hepatocyte nuclear factor 1 from muscle, HNF-1-alpha dimerization cofactor

All UniProt accessions (2): Q9H0N5, H0YA52

UniProt curated annotations — full annotation on UniProt →

Function. Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Regulates the dimerization of homeodomain protein HNF-1-alpha and enhances its transcriptional activity.

Subunit / interactions. Homotetramer. Interacts with DYRK1B.

Similarity. Belongs to the pterin-4-alpha-carbinolamine dehydratase family.

RefSeq proteins (1): NP_115527* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001533	Pterin_deHydtase	Family
IPR036428	PCD_sf	Homologous_superfamily

Pfam: PF01329

Enzyme classification (BRENDA):

• EC 4.2.1.96 — 4a-hydroxytetrahydrobiopterin dehydratase (BRENDA: 10 organisms, 27 substrates, 4 inhibitors, 31 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
6(S)-METHYL-7,8-DIHYDROPTERIN-4A-CARBINOLAMINE	0.007–2.2	14
(6R)-6-(L-ERYTHRO-1,2-DIHYDROXYPROPYL)-5,6,7,8-T	0.004–0.0053	4
4A(R)-HYDROXY-6(S)-METHYLTETRAHYDROPTERIN	0.006–390	3
4A(S)-HYDROXY-6(R)-METHYLTETRAHYDROPTERIN	0.0015–0.03	3
4A-HYDROXY-6(S)-METHYLTETRAHYDROPTERIN	0.0025–0.003	2
4A-HYDROXYTETRAHYDROBIOPTERIN	0.0047–0.0052	2
4A(R)-HYDROXY-6(S)-PROPYLTETRAHYDROPTERIN	0.0015	1
4A-HYDROXY-6(S)-PROPYLTETRAHYDROPTERIN	0.0013	1

Catalyzed reactions (Rhea), 1 shown:

• (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin = (6R)-L-erythro-6,7-dihydrobiopterin + H2O (RHEA:11920)

UniProt features (16 total): modified residue 6, strand 4, helix 3, chain 1, turn 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4C45	X-RAY DIFFRACTION	1.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0N5-F1	87.92	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 114, 114, 118, 118, 125, 125

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_PTERIDINE_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_PTERIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_DIOL_METABOLIC_PROCESS, GOMF_HYDRO_LYASE_ACTIVITY, DANG_BOUND_BY_MYC, GOBP_ALCOHOL_BIOSYNTHETIC_PROCESS, GOBP_POLYOL_BIOSYNTHETIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS, chr5q31, CASTELLANO_NRAS_TARGETS_UP, COLINA_TARGETS_OF_4EBP1_AND_4EBP2, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C

GO Biological Process (2): tetrahydrobiopterin biosynthetic process (GO:0006729), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (3): 4-alpha-hydroxytetrahydrobiopterin dehydratase activity (GO:0008124), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
diol biosynthetic process	1
pteridine-containing compound biosynthetic process	1
tetrahydrobiopterin metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
hydro-lyase activity	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCBD2	CATSPER3	Q86XQ3	935
PCBD2	DYRK1B	Q9Y463	854
PCBD2	HNF1A	P20823	757
PCBD2	CACNA1I	Q9P0X4	639
PCBD2	DYRK1A	Q13627	494
PCBD2	IFT22	Q9H7X7	445
PCBD2	MAP2K3	P46734	441
PCBD2	SLCO6A1	Q86UG4	436
PCBD2	QDPR	P09417	431
PCBD2	TXNDC15	Q96J42	418
PCBD2	GCH1	P30793	410
PCBD2	MTF2	Q9Y483	408
PCBD2	ZFHX4	Q86UP3	408
PCBD2	RCHY1	Q96PM5	394
PCBD2	RASSF5	Q8WWW0	394

IntAct

73 interactions, top by confidence:

A	B	Type	Score
HNF1A	PCBD2	psi-mi:“MI:0914”(association)	0.760
PCBD2	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
MAGEA11	PCBD2	psi-mi:“MI:0915”(physical association)	0.560
MAGEA6	PCBD2	psi-mi:“MI:0915”(physical association)	0.560
LGALS14	PCBD2	psi-mi:“MI:0915”(physical association)	0.560
KLC3	PCBD2	psi-mi:“MI:0915”(physical association)	0.560
PCBD2	SPG21	psi-mi:“MI:0915”(physical association)	0.560
GUCD1	PCBD2	psi-mi:“MI:0915”(physical association)	0.560
BCAS2	PCBD2	psi-mi:“MI:0915”(physical association)	0.560
PCBD2	MRFAP1	psi-mi:“MI:0915”(physical association)	0.560
CERS3	PCBD2	psi-mi:“MI:0915”(physical association)	0.560
PCBD1	PCBD2	psi-mi:“MI:0915”(physical association)	0.550
DYRK1B	PCBD2	psi-mi:“MI:0915”(physical association)	0.530
DYRK1B	PCBD2	psi-mi:“MI:0407”(direct interaction)	0.530
HNF1A	HSPA4L	psi-mi:“MI:0914”(association)	0.420
PCBD2	METAP2	psi-mi:“MI:0915”(physical association)	0.400
CHAF1A	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
SSX3	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
C1D	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
SNW1	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
ZZZ3	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
IRF2BP1	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
AATF	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
MED4	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
GTF2E1	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
BRF1	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
KCNIP3	PCBD2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (55): PCBD2 (Two-hybrid), PCBD2 (Reconstituted Complex), PCBD2 (Affinity Capture-MS), PCBD2 (Biochemical Activity), PCBD2 (Two-hybrid), PCBD2 (Two-hybrid), PCBD2 (Two-hybrid), PCBD2 (Two-hybrid), GUCD1 (Two-hybrid), CERS3 (Two-hybrid), MRFAP1 (Two-hybrid), MAGEA11 (Two-hybrid), MAGEA6 (Two-hybrid), PCBD2 (Affinity Capture-MS), METAP2 (Affinity Capture-MS)

ESM2 similar proteins: A1L1P7, A6ZSH0, B3LPE4, B3MRT7, B3NYF7, B4H303, B4IMF6, B4JWR9, B4M375, B4NE93, B4PZ52, B4R3T1, B5DKJ8, B5VQB0, B5YM03, B7FRE8, C5DGG6, D3ZYW7, I7HD01, O14561, O35943, O76454, O94255, P42797, P42844, P52505, P54150, P54151, Q05B87, Q07540, Q0IH40, Q0MQC2, Q0MQC3, Q16595, Q18680, Q38853, Q6QJ72, Q756Q4, Q84WZ8, Q8HXX9

Diamond homologs: A0K2V4, A0M1H4, A1SSU3, A2BVF3, A2C7K4, A4JA07, A4YJY8, A5E8P9, A5FWK8, A5GMR6, A5V667, A5VN26, A6UE17, A6VSD2, A6WV21, A7HSX5, A8LKP0, A9AJD5, A9M6T4, B0CIJ4, B0T207, B1K1I7, B1YQ64, B1ZY08, B2S7X9, B2T7M8, B2UGY6, B3Q9E4, B4E566, B4RBN1, B4RXT2, B5ZTF5, B6JAT9, B8GYB5, B9JCJ2, B9JUA0, C0RGE2, C3MAI8, O42658, O73930

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription initiation by RNA polymerase II	6	34.0×	9e-06
somatic stem cell population maintenance	5	25.8×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

26 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2400 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134959035:TGCA:T	acceptor_loss	1.0000
5:134959036:GCA:G	acceptor_loss	1.0000
5:134959037:CAGG:C	acceptor_loss	1.0000
5:134959038:A:G	acceptor_loss	1.0000
5:134959039:GGC:G	acceptor_gain	1.0000
5:134959117:CAAGG:C	donor_loss	1.0000
5:134959118:AAGG:A	donor_loss	1.0000
5:134959119:AGGT:A	donor_loss	1.0000
5:134959120:GGTAA:G	donor_loss	1.0000
5:134959121:GTA:G	donor_loss	1.0000
5:134959122:T:A	donor_loss	1.0000
5:134968086:T:G	donor_gain	1.0000
5:134968086:T:TG	donor_gain	1.0000
5:134968090:G:GG	donor_gain	1.0000
5:134996271:A:AG	acceptor_gain	1.0000
5:134996272:G:GG	acceptor_gain	1.0000
5:134905220:CATGG:C	donor_loss	0.9900
5:134905221:ATGGT:A	donor_loss	0.9900
5:134905223:GGT:G	donor_loss	0.9900
5:134905224:G:A	donor_loss	0.9900
5:134905224:G:GG	donor_gain	0.9900
5:134905225:T:A	donor_loss	0.9900
5:134905226:GAGT:G	donor_loss	0.9900
5:134910333:A:AG	acceptor_gain	0.9900
5:134910334:G:GA	acceptor_gain	0.9900
5:134910462:ATCAG:A	donor_loss	0.9900
5:134910463:TCAG:T	donor_loss	0.9900
5:134910464:CAG:C	donor_loss	0.9900
5:134910465:AGGTA:A	donor_loss	0.9900
5:134910466:GG:G	donor_loss	0.9900

AlphaMissense

843 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:134959073:G:C	A84P	0.994
5:134959100:T:A	W93R	0.993
5:134959100:T:C	W93R	0.993
5:134910458:T:C	F70L	0.992
5:134910460:T:A	F70L	0.992
5:134910460:T:G	F70L	0.992
5:134959049:T:C	F76L	0.990
5:134959051:T:A	F76L	0.990
5:134959051:T:G	F76L	0.990
5:134910404:T:A	W52R	0.989
5:134910404:T:C	W52R	0.989
5:134959043:T:C	F74L	0.989
5:134959045:T:A	F74L	0.989
5:134959045:T:G	F74L	0.989
5:134959062:T:A	V80D	0.988
5:134959065:C:A	A81D	0.988
5:134960593:T:A	I102K	0.988
5:134959050:T:C	F76S	0.986
5:134960647:C:A	A120D	0.985
5:134910406:G:C	W52C	0.984
5:134910406:G:T	W52C	0.984
5:134959091:C:G	H90D	0.983
5:134960593:T:G	I102R	0.983
5:134910439:A:C	K63N	0.982
5:134910439:A:T	K63N	0.982
5:134959102:G:C	W93C	0.981
5:134959102:G:T	W93C	0.981
5:134959108:T:A	N95K	0.981
5:134959108:T:G	N95K	0.981
5:134910449:T:C	F67L	0.980

dbSNP variants (sampled 300 via entrez): RS1000029015 (5:134905712 T>C), RS1000034304 (5:134909848 C>A,T), RS1000062864 (5:134952171 G>A,T), RS1000082659 (5:134951590 A>G), RS1000138151 (5:134953976 T>C), RS1000159868 (5:134961442 C>T), RS1000167554 (5:134928469 G>A,T), RS1000243045 (5:134935796 A>G), RS1000256219 (5:134907877 C>T), RS1000357766 (5:134921296 T>C), RS1000416110 (5:134914513 A>G), RS1000515250 (5:134946909 T>G), RS1000533773 (5:134913206 A>C), RS1000547279 (5:134956456 G>A), RS1000567737 (5:134906352 C>T)

Disease associations

OMIM: gene MIM:609836 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000175_35	Height	8.000000e-06
GCST001792_5	Colorectal cancer	4.000000e-10
GCST001792_7	Colorectal cancer	1.000000e-10
GCST001958_2	Bulimia nervosa	3.000000e-06
GCST002352_31	Type 2 diabetes	2.000000e-06
GCST008163_526	Height	9.000000e-11
GCST012490_104	Femur bone mineral density x serum urate levels interaction	9.000000e-09
GCST012490_438	Femur bone mineral density x serum urate levels interaction	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
bisphenol A	increases expression	1
trichostatin A	affects expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Dronabinol	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.