PPCDC

Summary

PPCDC (phosphopantothenoylcysteine decarboxylase, HGNC:28107) is a protein-coding gene on chromosome 15q24.2, encoding Phosphopantothenoylcysteine decarboxylase (Q96CD2). Catalyzes the decarboxylation of the cysteine moiety of 4-phosphopantothenoylcysteine to form 4’-phosphopantotheine and this reaction forms part of the biosynthesis of coenzyme A. It is a selective cancer dependency (DepMap: 15.0% of cell lines).

Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. PPCDC (EC 4.1.1.36), one of the last enzymes in this pathway, converts phosphopantothenoylcysteine to 4-prime-phosphopantetheine (Daugherty et al., 2002 [PubMed 11923312]).

Source: NCBI Gene 60490 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Limited, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 43 total
• GTEx eGene: eQTL in 48 tissues, sQTL in 13 (q < 0.05)
• Cancer dependency (DepMap): dependent in 15.0% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.32 (unconstrained)
• MANE Select transcript: NM_021823

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28107
Approved symbol	PPCDC
Name	phosphopantothenoylcysteine decarboxylase
Location	15q24.2
Locus type	gene with protein product
Status	Approved
Aliases	MDS018, FLJ14585
Ensembl gene	ENSG00000138621
Ensembl biotype	protein_coding
OMIM	609854
Entrez	60490

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 16 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000342932

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 1, TSL 4: 1, TSL 5: 4

ENST00000342932, ENST00000562095, ENST00000562192, ENST00000563298, ENST00000563393, ENST00000564923, ENST00000564953, ENST00000567336, ENST00000568207, ENST00000568649, ENST00000569562, ENST00000889947, ENST00000889948, ENST00000928390, ENST00000928391, ENST00000928392, ENST00000928393, ENST00000943486, ENST00000978640, ENST00001121635, ENST00001134348

RefSeq mRNA: 6 — MANE Select: NM_021823 NM_001301101, NM_001301102, NM_001301103, NM_001301104, NM_001301105, NM_021823

CCDS: CCDS10275, CCDS73759, CCDS73760, CCDS73761, CCDS76781

Canonical transcript exons

ENST00000342932 — 6 exons

Exon	Start	End
ENSE00001381226	75049150	75050726
ENSE00002598893	75023590	75023626
ENSE00003519225	75028247	75028453
ENSE00003599224	75048553	75048721
ENSE00003603188	75043441	75043536
ENSE00003645653	75044386	75044514

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 89.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0146 / max 907.1011, expressed in 1632 samples.

Highest expression (Bgee): blood, granulocyte, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, lower esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PPCDC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 48 tissues and its splicing (sQTL) in 13 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 61 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	7.5e-39	+0.81	15:75023634:G:A
Thyroid	eqtl	5.1e-34	+0.71	15:75023634:G:A
Skin Sun Exposed Lower leg	eqtl	6.2e-34	+0.66	15:75037754:G:T
Nerve Tibial	eqtl	4.9e-33	+0.57	15:75023634:G:A
Cells Cultured fibroblasts	eqtl	3.8e-31	+0.49	15:75023634:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.2e-29	+0.69	15:75012413:C:T
Colon Sigmoid	eqtl	1.1e-25	+0.72	15:75012413:C:T
Adipose Visceral Omentum	eqtl	1.4e-25	+0.76	15:75012413:C:T
Testis	eqtl	2.8e-25	+0.64	15:75012413:C:T
Muscle Skeletal	eqtl	3.4e-24	+0.53	15:75037754:G:T
Artery Tibial	eqtl	1.5e-23	+0.48	15:75023634:G:A
Breast Mammary Tissue	eqtl	1.1e-22	+0.66	15:74998371:C:T
Heart Atrial Appendage	eqtl	5.0e-22	+0.70	15:75029569:C:T
Stomach	eqtl	1.7e-21	+0.65	15:75023634:G:A
Colon Transverse	eqtl	3.7e-21	+0.54	15:75012413:C:T
Esophagus Muscularis	eqtl	7.5e-19	+0.60	15:75012413:C:T
Artery Aorta	eqtl	7.8e-14	+0.55	15:75037754:G:T
Heart Left Ventricle	eqtl	1.5e-13	+0.67	15:75037754:G:T
Liver	eqtl	1.8e-12	+0.71	15:75012413:C:T
Pituitary	eqtl	3.4e-12	+0.68	15:75012413:C:T

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
147758	3.1351	1538
147761	1.9965	169
147760	1.7178	213
147757	0.5294	263
147763	0.5038	70
147762	0.1320	26

Top tissues by expression

showing 100 of 276 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	89.76	gold quality
granulocyte	CL:0000094	89.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.46	gold quality
lower esophagus mucosa	UBERON:0035834	87.52	gold quality
monocyte	CL:0000576	87.48	gold quality
mucosa of transverse colon	UBERON:0004991	87.38	gold quality
right adrenal gland	UBERON:0001233	87.36	gold quality
leukocyte	CL:0000738	87.14	gold quality
mononuclear cell	CL:0000842	87.14	gold quality
left adrenal gland	UBERON:0001234	86.80	gold quality
right adrenal gland cortex	UBERON:0035827	86.68	gold quality
left adrenal gland cortex	UBERON:0035825	86.49	gold quality
body of pancreas	UBERON:0001150	86.16	gold quality
esophagus mucosa	UBERON:0002469	85.50	gold quality
adrenal cortex	UBERON:0001235	85.05	gold quality
adrenal gland	UBERON:0002369	85.00	gold quality
spleen	UBERON:0002106	84.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.88	gold quality
pancreas	UBERON:0001264	82.95	gold quality
esophagus	UBERON:0001043	82.86	gold quality
tibial nerve	UBERON:0001323	82.85	gold quality
left coronary artery	UBERON:0001626	82.68	gold quality
body of stomach	UBERON:0001161	82.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.62	gold quality
right lobe of liver	UBERON:0001114	82.59	gold quality
minor salivary gland	UBERON:0001830	82.44	gold quality
popliteal artery	UBERON:0002250	82.37	gold quality
tibial artery	UBERON:0007610	82.35	gold quality
right lobe of thyroid gland	UBERON:0001119	82.27	gold quality
sural nerve	UBERON:0015488	82.25	gold quality
ascending aorta	UBERON:0001496	82.14	gold quality
aorta	UBERON:0000947	82.11	gold quality
thoracic aorta	UBERON:0001515	82.08	gold quality
upper lobe of left lung	UBERON:0008952	82.04	gold quality
left lobe of thyroid gland	UBERON:0001120	81.90	gold quality
transverse colon	UBERON:0001157	81.82	gold quality
gastrocnemius	UBERON:0001388	81.76	gold quality
lymph node	UBERON:0000029	81.70	gold quality
amniotic fluid	UBERON:0000173	81.59	gold quality
apex of heart	UBERON:0002098	81.45	gold quality
coronary artery	UBERON:0001621	81.44	gold quality
rectum	UBERON:0001052	81.42	gold quality
muscle of leg	UBERON:0001383	81.27	gold quality
gall bladder	UBERON:0002110	81.24	gold quality
spinal cord	UBERON:0002240	81.13	gold quality
metanephros cortex	UBERON:0010533	81.01	gold quality
descending thoracic aorta	UBERON:0002345	80.92	gold quality
thyroid gland	UBERON:0002046	80.91	gold quality
ectocervix	UBERON:0012249	80.91	gold quality
omental fat pad	UBERON:0010414	80.90	gold quality
peritoneum	UBERON:0002358	80.84	gold quality
saliva-secreting gland	UBERON:0001044	80.60	gold quality
stomach	UBERON:0000945	80.56	gold quality
mouth mucosa	UBERON:0003729	80.49	gold quality
upper lobe of lung	UBERON:0008948	80.39	gold quality
body of uterus	UBERON:0009853	80.37	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.37	gold quality
right lung	UBERON:0002167	80.28	gold quality
lower esophagus	UBERON:0013473	80.25	gold quality
endocervix	UBERON:0000458	80.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.23	gold quality
islet of Langerhans	UBERON:0000006	80.21	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.20	gold quality
left ovary	UBERON:0002119	80.16	gold quality
adenohypophysis	UBERON:0002196	79.80	gold quality
bone marrow cell	CL:0002092	79.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.79	gold quality
right uterine tube	UBERON:0001302	79.71	gold quality
right ovary	UBERON:0002118	79.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.40	gold quality
vermiform appendix	UBERON:0001154	79.39	gold quality
right coronary artery	UBERON:0001625	79.28	gold quality
prostate gland	UBERON:0002367	79.07	gold quality
colonic epithelium	UBERON:0000397	78.98	gold quality
ventricular zone	UBERON:0003053	78.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.89	gold quality
skin of leg	UBERON:0001511	78.78	gold quality
right atrium auricular region	UBERON:0006631	78.76	gold quality
tonsil	UBERON:0002372	78.72	gold quality
skin of abdomen	UBERON:0001416	78.63	gold quality
vagina	UBERON:0000996	78.54	gold quality
small intestine	UBERON:0002108	78.32	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.04	gold quality
heart left ventricle	UBERON:0002084	78.03	gold quality
adrenal tissue	UBERON:0018303	77.98	gold quality
prefrontal cortex	UBERON:0000451	77.87	gold quality
left uterine tube	UBERON:0001303	77.84	gold quality
periodontal ligament	UBERON:0008266	77.84	gold quality
colon	UBERON:0001155	77.83	gold quality
pituitary gland	UBERON:0000007	77.81	gold quality
esophagus squamous epithelium	UBERON:0006920	77.63	gold quality
ovary	UBERON:0000992	77.62	gold quality
ganglionic eminence	UBERON:0004023	77.34	gold quality
intestine	UBERON:0000160	77.27	gold quality
cardiac ventricle	UBERON:0002082	77.21	gold quality
large intestine	UBERON:0000059	77.17	gold quality
mucosa of stomach	UBERON:0001199	77.02	gold quality
stromal cell of endometrium	CL:0002255	77.01	gold quality
anterior cingulate cortex	UBERON:0009835	76.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.06

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Parathyroid gland	tissue	20.0	medium
Bone marrow	tissue	18.6	low
Lymph node	tissue	15.3	medium
Frontal cortex	tissue	14.4
Choroid plexus	tissue	13.7
Salivary gland	tissue	13.1	medium
Adrenal gland	tissue	12.7	high
Caudate putamen	tissue	12.2
Esophagus	tissue	11.6	low
Tonsil	tissue	11.5	high
Spleen	tissue	11.4	high
Thymus	tissue	11.2
Locus coeruleus	tissue	11.1
Colon	tissue	10.7	high
Stomach 1	tissue	10.6	high
Urinary bladder	tissue	10.5	medium
Adipose tissue	tissue	10.4	not detected
Fallopian tube	tissue	10.2	medium
Appendix	tissue	10.2	high
Vagina	tissue	9.6	medium
Pancreas	tissue	9.3	medium
Small intestine	tissue	9.3	high
Epididymis	tissue	9.2	high
Duodenum	tissue	9.1	high
Pituitary gland	tissue	8.8
Rectum	tissue	8.8	medium
Placenta	tissue	8.7	medium
Breast	tissue	8.6	medium
Lung	tissue	8.6	high
Ovary	tissue	8.5	low
Thyroid gland	tissue	8.3	medium
Prostate	tissue	8.3	high
Nucleus accumbens	tissue	8.2
Skeletal muscle	tissue	7.9	high
Gallbladder	tissue	7.9	medium
Skin 1	tissue	7.8	low
Liver	tissue	7.8	medium
Hippocampus	tissue	7.8	medium
Kidney	tissue	7.4	high
Endometrium 1	tissue	7.3	medium
Retina	tissue	7.1
Seminal vesicle	tissue	7.1	medium
Cervix	tissue	6.9	medium
Testis	tissue	6.8	medium
Corpus callosum	tissue	6.6
Heart muscle	tissue	6.5	medium
Cerebral cortex	tissue	6.4	medium
Hippocampal formation	tissue	6.4
Entorhinal cortex	tissue	6.4
Somatosensory cortex	tissue	6.4
Occipital cortex	tissue	6.4
Insular cortex	tissue	6.3
Pons	tissue	6.1
Motor cortex	tissue	6.1
Substantia nigra	tissue	6.1
Prefrontal cortex	tissue	6.0
Medulla oblongata	tissue	6.0
Temporal cortex	tissue	6.0
Midbrain	tissue	5.9
Retrosplenial cortex	tissue	5.9

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Parieto-temporal junction (white matter) (16.2), Temporal white matter (16.1), Piriform cortex (14.9), Corpus callosum, genu (white matter) (14.6), Nucleus gracilis (14.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PPCDC by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 38 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-135A-2-3P	98.40	66.74	442
HSA-MIR-135B-3P	98.40	67.35	426
HSA-MIR-6776-3P	98.38	66.34	655
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299

Functional genomics

gnomAD constraint: pLI 1.03e-06, LOEUF 1.32, missense Z 0.747 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000342932 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
15:75,028,319–75,048,707	225 / 222.6	1.01	no
15:75,048,708–75,049,232	21 / 41.2	0.51	no
DepMap (CRISPR cell-line fitness): dependent in 15.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): NOZ (-1.996), PF-382 (-1.888), TANOUE (-1.813), WSU-NHL (-1.782), KCL-22 (-1.752), OCI-LY18 (-1.632), BC-1 (-1.541), SU-DHL-4 (-1.46), SNU-601 (-1.425), KMM-1 (-1.424), BLUE-1 (-1.423), NAMALWA (-1.408), AGS (-1.381), COLO-800 (-1.379), U-2946 (-1.357).

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppcdc	ENSDARG00000033020
mus_musculus	Ppcdc	ENSMUSG00000063849
rattus_norvegicus	Ppcdc	ENSRNOG00000053404
rattus_norvegicus	Ppcdc	ENSRNOG00000084814
drosophila_melanogaster	Ppcdc	FBGN0050290
caenorhabditis_elegans		WBGENE00009138

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Escherichia coli K-12	P0ABQ0	100.0%	Diamond
Escherichia coli CFT073	P0ABQ1	100.0%	Diamond
Mycobacterium tuberculosis variant bovis AF2122/97	P67734	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WNZ0	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WNZ1	100.0%	Diamond
Vibrio vulnificus YJ016	Q7MPS9	99.5%	Diamond
Vibrio vulnificus CMCP6	Q8DDX8	99.5%	Diamond
Glycine max	C6SZ50	95.7%	Diamond
Arabidopsis thaliana	P94063	86.5%	Diamond
Mycolicibacterium smegmatis MC2 155	A0QWT2	86.2%	Diamond
Vibrio parahaemolyticus RIMD 2210633	Q87T89	85.2%	Diamond
Malus domestica	A0A498JQK2	81.0%	Diamond
Oryza sativa Japonica Group	Q69K55	81.0%	Diamond
Vibrio cholerae O1 biovar El Tor str. N16961	Q9KVD1	78.9%	Diamond
Aliivibrio fischeri ES114	Q5E8M6	76.5%	Diamond
Candida tropicalis	Q12600	56.3%	Diamond
Saccharomyces cerevisiae S288C	P36024	54.6%	Diamond
unidentified prokaryotic organism	A0A2I9	53.5%	Diamond
Streptococcus mutans UA159	Q54433	52.1%	Diamond
Bacillus subtilis subsp. subtilis str. 168	O35033	47.5%	Diamond
Synechocystis sp. PCC 6803 substr. Kazusa	P73881	46.2%	Diamond
Dictyostelium discoideum	Q54Y51	45.0%	Diamond
Borreliella burgdorferi B31	O51752	43.4%	Diamond
Staphylococcus epidermidis	P30197	39.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SCAMP5	protein-coding	192683
RPP25	protein-coding	54913
MPI	protein-coding	4351
FAM219B	protein-coding	57184
COX5A	protein-coding	9377

Protein

Protein identifiers

Phosphopantothenoylcysteine decarboxylase — Q96CD2 (reviewed: Q96CD2)

Alternative names: CoaC

All UniProt accessions (7): Q96CD2, H3BPW5, H3BQB0, H3BRQ0, H3BSE3, H3BU34, H3BU63

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the decarboxylation of the cysteine moiety of 4-phosphopantothenoylcysteine to form 4’-phosphopantotheine and this reaction forms part of the biosynthesis of coenzyme A.

Subunit / interactions. Homotrimer.

Cofactor. Binds 1 FMN per subunit.

Pathway. Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-pantothenate: step 3/5.

Miscellaneous. The Met-1 codon is associated with a polymorphism (dbSNP:rs2304899) that replaces the initiation ATG codon by an ATA codon.

Similarity. Belongs to the HFCD (homooligomeric flavin containing Cys decarboxylase) superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96CD2-1	1	yes
Q96CD2-2	2

RefSeq proteins (6): NP_001288030, NP_001288031, NP_001288032, NP_001288033, NP_001288034, NP_068595* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003382	Flavoprotein	Domain
IPR036551	Flavin_trans-like	Homologous_superfamily

Pfam: PF02441

Enzyme classification (BRENDA)

• EC 4.1.1.36 — phosphopantothenoylcysteine decarboxylase (BRENDA: 20 organisms, 16 substrates, 18 inhibitors, 4 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-PHOSPHOPANTOTHENOYL-L-CYS	0.9–1.43	2
(R)-4’-PHOSPHO-N-PANTOTHENOYLCYSTEINE	0.118	1

Catalyzed reactions (Rhea)

• N-[(R)-4-phosphopantothenoyl]-L-cysteine + H(+) = (R)-4’-phosphopantetheine + CO2 (RHEA:16793)

UniProt features (24 total): helix 11, strand 4, binding site 3, chain 1, active site 1, splice variant 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
1QZU	crystal structure of human phosphopantothenoylcysteine decarboxylase	X-RAY DIFFRACTION	2.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CD2-F1	90.82	0.79

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Lyases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
173	proton donor

Ligand- & substrate-binding residues (3)

Position	Role
59	FMN
104–107	FMN
140	substrate

Mutagenesis-validated functional residues (1)

Position	Phenotype
173	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-196783	Coenzyme A biosynthesis	curated
R-HSA-1430728	Metabolism	—
R-HSA-196854	Metabolism of vitamins and cofactors	—
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors	—
R-HSA-199220	Vitamin B5 (pantothenate) metabolism	—

MSigDB gene sets: 182 (showing top): GOBP_COENZYME_A_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, MARTINEZ_RB1_TARGETS_DN, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, GOBP_COENZYME_A_BIOSYNTHETIC_PROCESS, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ACTWSNACTNY_UNKNOWN, GOMF_CARBOXY_LYASE_ACTIVITY

GO Biological Process (1): coenzyme A biosynthetic process (GO:0015937)

GO Molecular Function (7): phosphopantothenoylcysteine decarboxylase activity (GO:0004633), FMN binding (GO:0010181), identical protein binding (GO:0042802), catalytic activity (GO:0003824), protein binding (GO:0005515), lyase activity (GO:0016829), carboxy-lyase activity (GO:0016831)

GO Cellular Component (2): cytosol (GO:0005829), phosphopantothenoylcysteine decarboxylase complex (GO:0071513)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Vitamin B5 (pantothenate) metabolism	1
Metabolism of vitamins and cofactors	1
Metabolism	1
Metabolism of water-soluble vitamins and cofactors	1

GO top-level categories

15 GO namespaces:

Category	Terms
cytoplasm	2
coenzyme A metabolic process	1
sulfur compound biosynthetic process	1
purine-containing compound biosynthetic process	1
nucleoside phosphate biosynthetic process	1
carboxy-lyase activity	1
ribonucleotide binding	1
anion binding	1
protein binding	1
molecular_function	1
binding	1
catalytic activity	1
carbon-carbon lyase activity	1
cellular anatomical structure	1
catalytic complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
coenzyme A biosynthetic process	BP	direct assay
FMN binding	MF	direct assay
identical protein binding	MF	direct assay
phosphopantothenoylcysteine decarboxylase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 382 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPCDC	COASY	Q13057	969
PPCDC	PANK1	Q8TE04	639
PPCDC	PANK3	Q9H999	565
PPCDC	PANK2	Q9BZ23	523
PPCDC	PPCS	Q9HAB8	493
PPCDC	DUS1L	Q6P1R4	459
PPCDC	COQ6	Q9Y2Z9	440
PPCDC	RFK	Q969G6	425
PPCDC	HACL1	Q9UJ83	349
PPCDC	UPB1	Q9UBR1	330
PPCDC	PANK4	Q9NVE7	292
PPCDC	DPYS	Q14117	273
PPCDC	FPGS	Q05932	270
PPCDC	PPOX	P50336	269
PPCDC	GADL1	Q6ZQY3	260

IntAct

Human interaction partners of PPCDC in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
FOXR1	physical association	0.780	10
NTAQ1	physical association	0.720	6
TXN2	physical association	0.720	6
ZNF232	physical association	0.720	6
DDIT4L	physical association	0.560	3
GCD7	physical association	0.560	3
NAA80	physical association	0.560	3
PLEKHF2	physical association	0.560	3
PPIG	physical association	0.560	3
RNF8	physical association	0.560	3
SREK1IP1	physical association	0.560	3
TAE1	physical association	0.560	3
TGM7	physical association	0.560	3
UBE2I	physical association	0.560	3
VHS3	physical association	0.560	3
PSMA1	physical association	0.370	1
CENPT	physical association	0.000	1
DBI	physical association	0.000	1

BioGRID (29 interactions; top human partners by supporting records): ZNF232 (Two-hybrid; 3 records), FOXR1 (Two-hybrid; 2 records), TXN2 (Two-hybrid; 2 records), WDYHV1 (Two-hybrid; 2 records), DCPS (Affinity Capture-MS), DDIT4L (Two-hybrid), EGFR (Negative Genetic), KRAS (Negative Genetic), MFSD12 (Positive Genetic), NAT6 (Two-hybrid), NUDT21 (Affinity Capture-RNA), PARP8 (Proximity Label-MS), PLEKHF2 (Two-hybrid), PPIG (Two-hybrid), PSMA1 (Two-hybrid)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	PPCDC	ubiquitination

Disease & clinical

Genetic variants

Variant evidence for PPCDC: 43 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 17 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	5
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 470):

Position(s)	Effect	Δscore	Sites
15:75044384–75044385	acceptor_loss	1.0000	5
15:75043432	acceptor_gain	0.9900
15:75044385	acceptor_loss	0.9900
15:75048550	acceptor_gain	0.9900
15:75048551–75048552	acceptor_loss	0.9900	6
15:75043420	acceptor_gain	0.9800
15:75044380	acceptor_gain	0.9800
15:75048722–75048723	donor_loss	0.9800	5
15:75023627–75023628	donor_loss	0.9700	5
15:75044482	donor_gain	0.9600

AlphaMissense

537 missense substitutions predicted likely pathogenic (of 1,339 scored), across 128 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M143	9	0.940	0.990
M139	9	0.898	0.987
H88	8	0.963	0.990
N140	8	0.963	0.992
D104	8	0.939	0.974
F59	8	0.935	0.991
D117	8	0.927	0.979
S27	8	0.888	0.989
D175	8	0.754	0.898
W127	7	0.969	0.994
W76	7	0.957	0.989
W79	7	0.943	0.981
W144	7	0.940	0.981
E75	7	0.928	0.961
C173	7	0.923	0.978
W94	7	0.914	0.975
M181	7	0.905	0.965
C136	7	0.894	0.991
C116	7	0.882	0.994
D72	7	0.870	0.932

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.02e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000278
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000888
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.0009

Disease associations

OMIM: gene MIM:609854 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
dilated cardiomyopathy	Limited	Autosomal recessive

Mondo (1): dilated cardiomyopathy (MONDO:0005021)

GWAS associations

17 associations:

Study	Trait	p-value
GCST002040_2	Blood trace element (Zn levels)	2e-18
GCST010108_24	Coffee consumption (cups per day)	2e-17
GCST90002402_262	Platelet count	4e-17
GCST90002391_196	Mean corpuscular hemoglobin concentration	1e-15
GCST003155_16	Systemic lupus erythematosus	6e-15
GCST90002396_362	Mean reticulocyte volume	5e-13
GCST006979_1061	Heel bone mineral density	1e-12
GCST90002398_302	Neutrophil count	1e-12
GCST90002407_613	White blood cell count	5e-12
GCST90002406_12	Reticulocyte fraction of red cells	4e-11
GCST010108_23	Coffee consumption (cups per day)	1e-10
GCST90002388_340	Lymphocyte count	2e-9
GCST009153_1	Adverse response to chemotherapy (amenorrhea) in breast cancer	6e-9
GCST010241_285	Apolipoprotein A1 levels	6e-9
GCST012332_86	Multisite chronic pain	2e-8
GCST012332_87	Multisite chronic pain	2e-8
GCST001032_1	Caffeine consumption	6e-7

EFO canonical traits (from GWAS)

10 canonical traits:

EFO ID	Trait name
EFO:0004330	coffee consumption
EFO:0009270	heel bone mineral density
EFO:0006782	cups of coffee per day measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0010100	multisite chronic pain
EFO:0004587	lymphocyte count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0004309	platelet count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs147451859	Toxicity	3	docetaxel;FEC100;gemcitabine;trastuzumab;zoledronate	Amenorrhea

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs147451859	PPCDC	3	0.00	1	docetaxel;FEC100;gemcitabine;trastuzumab;zoledronate

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs147451859	docetaxel, FEC100, gemcitabine, trastuzumab, zoledronate	Toxicity	Allele G is associated with decreased likelihood of Amenorrhea when treated with docetaxel, FEC100, gemcitabine, trastuzumab and zoledronate in women with Breast Neoplasms as compared to allele C.	PMID:31371054

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	increases expression	1
Coumestrol	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases abundance, affects expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Zinc	affects abundance	1
Cyclosporine	increases expression	1
Copper Sulfate	affects expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 159 trials:

NCT	Phase	Status	Title
NCT00374465	Phase 4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	Phase 4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	Phase 4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	Phase 4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	Phase 4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	Phase 4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	Phase 3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	Phase 3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	Phase 3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	Phase 3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	Phase 3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	Phase 3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	Phase 3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	Phase 3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	Phase 3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	Phase 3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	Phase 2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	Phase 2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	Phase 2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	Phase 2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	Phase 2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	Phase 2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	Phase 2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	Phase 2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	Phase 2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	Phase 2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	Phase 2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	Phase 2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	Phase 2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	Phase 2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	Phase 1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	Phase 1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	Phase 1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	Phase 1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	Phase 1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	Phase 1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	Phase 1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT07137338	Phase 1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	Phase 1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy
NCT07516288	Phase 1	RECRUITING	Safety and Efficacy of Second Infusion of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT00743639	Phase 2/3	COMPLETED	Autologous Transplantation of Bone Marrow Mononuclear Stem-Cells for Dilated Cardiomyopathy
NCT01311791	Phase 2/3	COMPLETED	A Randomized, Controlled Study to Evaluate Algisyl-LVR™ as a Method of Left Ventricular Augmentation for Heart Failure
NCT02248532	Phase 2/3	COMPLETED	Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy (REMEDIUM)
NCT02652728	Phase 2/3	UNKNOWN	Orodispersible Minitablets of Enalapril in Children With Heart Failure Due to Dilated Cardiomyopathy
NCT02654678	Phase 2/3	UNKNOWN	Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril
NCT00454818	Phase 1/2	COMPLETED	Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure
NCT00615394	Phase 1/2	COMPLETED	Autologous Transplantation of Bone Marrow Mononuclear Stem-Cells by Mini-Thoracotomy
NCT01219452	Phase 1/2	UNKNOWN	Intramuscular Injection of Mesenchymal Stem Cell for Treatment of Children With Idiopathic Dilated Cardiomyopathy
NCT01290822	Phase 1/2	TERMINATED	Optimized Biventricular Pacing Allograft Recipients
NCT01739777	Phase 1/2	COMPLETED	Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy
NCT03447990	Phase 1/2	COMPLETED	v4 Study Evaluating the Safety, Tolerability and Preliminary Pharmacokinetics and Pharmacodynamics of MYK-491
NCT06902896	Phase 1/2	RECRUITING	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07347197	Phase 1/2	NOT_YET_RECRUITING	Endocardial Delivery for Myocardial Regeneration Using Allogeneic iPSC-derived Cardiomyocyte Spheroids for HF With Systolic Dysfunction (EMERALD Study)
NCT07426419	Phase 1/2	RECRUITING	An AAV Gene Therapy Trial of AFTX-201 in Adults With BAG3-Associated Dilated Cardiomyopathy (DCM)
NCT05837143	Early Phase 1	UNKNOWN	Myocardial Telomere Recapping Study for Dilated Cardiomyopathy
NCT00001313	Not specified	COMPLETED	Evaluation of Patients With Known or Suspected Heart Disease
NCT00180323	Not specified	COMPLETED	ACC - Atrial Contribution to CRT
NCT00208806	Not specified	COMPLETED	Resynchronization Therapy in Young Patients With and Without CHD
NCT00282789	Not specified	COMPLETED	BiPAP for Cardiomyopathy With Central Sleep Apnea
NCT00466713	Not specified	TERMINATED	Defining the Role of Insulin Resistance in ‘Idiopathic’ Dilated Cardiomyopathy