PPCS

Summary

PPCS (phosphopantothenoylcysteine synthetase, HGNC:25686) is a protein-coding gene on chromosome 1p34.2, encoding Phosphopantothenate–cysteine ligase (Q9HAB8). Catalyzes the second step in the biosynthesis of coenzyme A from vitamin B5, where cysteine is conjugated to 4’-phosphopantothenate to form 4-phosphopantothenoylcysteine. It is a selective cancer dependency (DepMap: 16.6% of cell lines).

Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. PPCS (EC 6.3.2.5), one of the last enzymes in this pathway, converts phosphopantothenate to phosphopantothenoylcysteine (Daugherty et al., 2002 [PubMed 11923312]).

Source: NCBI Gene 79717 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiomyopathy, dilated, 2c (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 18 total
• GTEx eGene: eQTL in 9 tissues, sQTL in 10 (q < 0.05)
• Phenotypes (HPO): 23
• Cancer dependency (DepMap): dependent in 16.6% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.06 (unconstrained)
• MANE Select transcript: NM_024664

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25686
Approved symbol	PPCS
Name	phosphopantothenoylcysteine synthetase
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11838
Ensembl gene	ENSG00000127125
Ensembl biotype	protein_coding
OMIM	609853
Entrez	79717

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000372561

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

ENST00000372561, ENST00000372556, ENST00000372560, ENST00000372562, ENST00000469615, ENST00000471420, ENST00000472013, ENST00000482168, ENST00000933676, ENST00000983779, ENST00000983780, ENST00000983781, ENST00000983782, ENST00000983783, ENST00000983785, ENST00000983786, ENST00001053122, ENST00001053123, ENST00001061187, ENST00001099786, ENST00001099787, ENST00001143277

RefSeq mRNA: 7 — MANE Select: NM_024664 NM_001077447, NM_001287506, NM_001287508, NM_001287509, NM_001287510, NM_001287511, NM_024664

CCDS: CCDS41311, CCDS41312

Canonical transcript exons

ENST00000372561 — 3 exons

Exon	Start	End
ENSE00001901576	42456543	42457073
ENSE00003519305	42459603	42461236
ENSE00003645615	42457247	42457350

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 97.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.4210 / max 287.8256, expressed in 1824 samples.

Highest expression (Bgee): adrenal gland cortex, body of pancreas, adrenal gland, calcaneal tendon, rectum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PPCS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.5e-04	+0.36	1:42565254:T:C
Skin Not Sun Exposed Suprapubic	sqtl	1.6e-04	+0.36	1:42627521:A:G
Whole Blood	sqtl	2.2e-04	-0.24	1:42531033:T:C
Artery Aorta	eqtl	1.4e-03	+0.11	1:42556139:C:T
Stomach	eqtl	2.4e-03	+0.11	1:42446634:A:C
Artery Tibial	eqtl	3.1e-03	+0.10	1:42444953:A:G
Esophagus Mucosa	sqtl	5.8e-03	-0.28	1:42500879:G:A
Cells EBV-transformed lymphocytes	sqtl	8.1e-03	-0.58	1:42517787:G:A
Thyroid	sqtl	8.9e-03	-0.25	1:42450056:C:G
Skin Sun Exposed Lower leg	eqtl	1.2e-02	+0.08	1:41770333:T:C
Skin Not Sun Exposed Suprapubic	eqtl	1.7e-02	-0.33	1:42957310:A:C
Skin Sun Exposed Lower leg	sqtl	1.9e-02	+0.26	1:42446480:C:T
Muscle Skeletal	sqtl	2.3e-02	-0.22	1:42420514:A:G
Brain Spinal cord cervical c-1	eqtl	2.4e-02	+0.23	1:42440989:A:G
Adipose Subcutaneous	sqtl	3.0e-02	+1.11	1:42736457:A:C
Testis	eqtl	3.0e-02	-0.08	1:41592058:G:A
Heart Left Ventricle	sqtl	3.1e-02	+1.13	1:41993916:C:T
Whole Blood	eqtl	3.2e-02	+0.23	1:42855530:C:T
Uterus	sqtl	4.7e-02	-0.74	1:42330430:G:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
2457	38.4210	1824

Top tissues by expression

showing 100 of 286 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	97.05	gold quality
body of pancreas	UBERON:0001150	97.04	gold quality
right adrenal gland	UBERON:0001233	96.91	gold quality
calcaneal tendon	UBERON:0003701	96.88	gold quality
rectum	UBERON:0001052	96.82	gold quality
mucosa of transverse colon	UBERON:0004991	96.70	gold quality
monocyte	CL:0000576	96.61	gold quality
mononuclear cell	CL:0000842	96.49	gold quality
leukocyte	CL:0000738	96.44	gold quality
left adrenal gland	UBERON:0001234	96.38	gold quality
left adrenal gland cortex	UBERON:0035825	96.16	gold quality
adrenal tissue	UBERON:0018303	96.04	gold quality
body of stomach	UBERON:0001161	96.02	gold quality
metanephros cortex	UBERON:0010533	96.02	gold quality
gall bladder	UBERON:0002110	95.98	gold quality
tendon	UBERON:0000043	95.79	gold quality
transverse colon	UBERON:0001157	95.79	gold quality
minor salivary gland	UBERON:0001830	95.72	gold quality
right coronary artery	UBERON:0001625	95.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.41	gold quality
pancreas	UBERON:0001264	95.39	gold quality
granulocyte	CL:0000094	95.35	gold quality
adrenal cortex	UBERON:0001235	95.35	gold quality
adrenal gland	UBERON:0002369	95.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.30	gold quality
saliva-secreting gland	UBERON:0001044	95.25	gold quality
skin of abdomen	UBERON:0001416	95.04	gold quality
adult mammalian kidney	UBERON:0000082	95.00	gold quality
left coronary artery	UBERON:0001626	94.96	gold quality
esophagus mucosa	UBERON:0002469	94.90	gold quality
right lobe of thyroid gland	UBERON:0001119	94.84	gold quality
duodenum	UBERON:0002114	94.80	gold quality
left lobe of thyroid gland	UBERON:0001120	94.79	gold quality
colon	UBERON:0001155	94.79	gold quality
large intestine	UBERON:0000059	94.74	gold quality
endocervix	UBERON:0000458	94.73	gold quality
stomach	UBERON:0000945	94.72	gold quality
lower esophagus	UBERON:0013473	94.72	gold quality
esophagus	UBERON:0001043	94.71	gold quality
skin of leg	UBERON:0001511	94.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.71	gold quality
intestine	UBERON:0000160	94.69	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.65	gold quality
prostate gland	UBERON:0002367	94.61	gold quality
mouth mucosa	UBERON:0003729	94.57	gold quality
tibial artery	UBERON:0007610	94.57	gold quality
small intestine	UBERON:0002108	94.55	gold quality
popliteal artery	UBERON:0002250	94.55	gold quality
right lobe of liver	UBERON:0001114	94.51	gold quality
descending thoracic aorta	UBERON:0002345	94.49	gold quality
thyroid gland	UBERON:0002046	94.44	gold quality
ectocervix	UBERON:0012249	94.39	gold quality
aorta	UBERON:0000947	94.38	gold quality
mucosa of stomach	UBERON:0001199	94.36	gold quality
thoracic aorta	UBERON:0001515	94.35	gold quality
adipose tissue	UBERON:0001013	94.34	gold quality
ascending aorta	UBERON:0001496	94.29	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.26	gold quality
omental fat pad	UBERON:0010414	94.24	gold quality
spleen	UBERON:0002106	94.22	gold quality
coronary artery	UBERON:0001621	94.21	gold quality
peritoneum	UBERON:0002358	94.21	gold quality
islet of Langerhans	UBERON:0000006	94.19	gold quality
connective tissue	UBERON:0002384	94.12	gold quality
tendon of biceps brachii	UBERON:0008188	94.10	gold quality
zone of skin	UBERON:0000014	94.08	gold quality
right lung	UBERON:0002167	94.07	gold quality
right uterine tube	UBERON:0001302	94.02	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.00	gold quality
left uterine tube	UBERON:0001303	93.96	gold quality
parotid gland	UBERON:0001831	93.95	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	93.83	gold quality
vagina	UBERON:0000996	93.82	gold quality
right atrium auricular region	UBERON:0006631	93.68	gold quality
body of uterus	UBERON:0009853	93.57	gold quality
tibial nerve	UBERON:0001323	93.56	gold quality
vermiform appendix	UBERON:0001154	93.55	gold quality
colonic epithelium	UBERON:0000397	93.41	gold quality
nasal cavity mucosa	UBERON:0001826	93.41	gold quality
kidney	UBERON:0002113	93.26	gold quality
right ovary	UBERON:0002118	93.21	gold quality
colonic mucosa	UBERON:0000317	93.19	gold quality
cortex of kidney	UBERON:0001225	93.09	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.04	gold quality
left ovary	UBERON:0002119	93.03	gold quality
upper lobe of left lung	UBERON:0008952	92.89	gold quality
skin of hip	UBERON:0001554	92.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.84	gold quality
cardiac atrium	UBERON:0002081	92.84	gold quality
adenohypophysis	UBERON:0002196	92.81	gold quality
palpebral conjunctiva	UBERON:0001812	92.80	gold quality
metanephros	UBERON:0000081	92.76	gold quality
nasal cavity epithelium	UBERON:0005384	92.75	silver quality
heart left ventricle	UBERON:0002084	92.69	gold quality
muscle of leg	UBERON:0001383	92.65	gold quality
liver	UBERON:0002107	92.64	gold quality
heart	UBERON:0000948	92.62	gold quality
fundus of stomach	UBERON:0001160	92.59	gold quality
gastrocnemius	UBERON:0001388	92.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	496.16
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	93.1	low
Kidney	tissue	82.1	medium
Epididymis	tissue	67.1	low
Pancreas	tissue	63.0	medium
Stomach 1	tissue	61.1	medium
Breast	tissue	61.0	low
Thyroid gland	tissue	60.7	medium
Colon	tissue	59.5	medium
Parathyroid gland	tissue	56.2	low
Salivary gland	tissue	56.0	medium
Rectum	tissue	54.6	medium
Duodenum	tissue	54.6	medium
Small intestine	tissue	53.0	medium
Prostate	tissue	49.1	low
Adipose tissue	tissue	47.6	low
Adrenal gland	tissue	47.4	medium
Vagina	tissue	43.4	medium
Skeletal muscle	tissue	42.6	medium
Seminal vesicle	tissue	41.7	medium
Cervix	tissue	41.5	low
Esophagus	tissue	41.2	medium
Lymph node	tissue	40.7	low
Gallbladder	tissue	40.4	medium
Heart muscle	tissue	39.8	medium
Skin 1	tissue	38.7	medium
Choroid plexus	tissue	38.4
Urinary bladder	tissue	38.3	medium
Tongue	tissue	37.7
Lung	tissue	37.6	medium
Tonsil	tissue	35.8	low
Placenta	tissue	35.7	medium
Ovary	tissue	35.2	medium
Spleen	tissue	32.9	low
Appendix	tissue	32.6	medium
Pituitary gland	tissue	29.4
Endometrium 1	tissue	29.4	low
Fallopian tube	tissue	28.2	medium
Smooth muscle	tissue	27.1	medium
Thymus	tissue	25.9
Bone marrow	tissue	25.9	medium
Locus coeruleus	tissue	21.7
Retina	tissue	21.0
Nucleus accumbens	tissue	19.1
Hippocampus	tissue	18.1	low
Postcentral gyrus	tissue	16.0
Testis	tissue	14.1	low
Frontal cortex	tissue	9.0
Spinal cord	tissue	8.8
Thalamus	tissue	8.0
Pons	tissue	7.9
Substantia nigra	tissue	7.9
Superior colliculi	tissue	7.8
Medulla oblongata	tissue	7.5
Hypothalamus	tissue	7.5
Caudate putamen	tissue	7.5
Midbrain	tissue	7.4
Hippocampal formation	tissue	7.4
Septum	tissue	7.4
Cerebral cortex	tissue	7.2	low
Temporal cortex	tissue	7.2

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (49.8), Lateral funiculus (white matter) (30.3), Supraoptic nucleus (28.9), Cervical spinal cord, ventral horn (27.9), Dorsal funiculus (white matter) (27.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

showing 30 of 69 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-7856-5P	99.75	69.99	2901

Functional genomics

gnomAD constraint: pLI 6.35e-05, LOEUF 1.06, missense Z 0.82 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000372561 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
1:42,456,566–42,457,253	244 / 234.7	1.04	no
1:42,457,254–42,459,923	116 / 168.1	0.69	no
DepMap (CRISPR cell-line fitness): dependent in 16.6% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SU-DHL-10 (-1.936), SU-DHL-8 (-1.753), TUHR10TKB (-1.346), BC-1 (-1.333), 697 (-1.3), OCI-LY-19 (-1.237), ST486 (-1.216), BLUE-1 (-1.209), NAMALWA (-1.192), BC-3 (-1.138), SLR 24 (-1.078), SU-DHL-5 (-1.078), MOLM-14 (-1.062), ARH-77 (-1.057), COLO 205 (-1.045).

Literature-anchored findings (GeneRIF, showing 2)

• Oxygen transfer studies found that 18O from [carboxyl-18O] phosphopantothenate is incorporated into AMP or CMP produced during PPCS catalysis, consistent with the formation of a phosphopantothenoyl cytidylate or phosphopantothenoyl adenylate intermediate (PMID:19683078)
• Exome sequencing in five individuals from two unrelated families presenting with dilated cardiomyopathy revealed biallelic mutations in PPCS. (PMID:29754768)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppcs	ENSDARG00000061889
mus_musculus	Ppcs	ENSMUSG00000028636
rattus_norvegicus	Ppcs	ENSRNOG00000008572
drosophila_melanogaster	Ppcs	FBGN0261285
caenorhabditis_elegans		WBGENE00022171

Paralogs (4): CNIH1 (ENSG00000100528), CNIH4 (ENSG00000143771), CNIH3 (ENSG00000143786), CNIH2 (ENSG00000174871)

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
Arabidopsis thaliana	Q8GXR5	87.0%	Diamond
Oryza sativa Japonica Group	Q0J7N5	67.1%	Diamond
Schizosaccharomyces pombe 972h-	Q9USK7	46.4%	Diamond
Saccharomyces cerevisiae S288C	P40506	45.9%	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
CCDC30	protein-coding	728621
ZMYND12	protein-coding	84217
FOXJ3	protein-coding	22887
RIMKLA	protein-coding	284716
GUCA2A	protein-coding	2980
PPIH	protein-coding	10465
YBX1	protein-coding	4904

Protein

Protein identifiers

Phosphopantothenate–cysteine ligase — Q9HAB8 (reviewed: Q9HAB8)

Alternative names: Phosphopantothenoylcysteine synthetase

All UniProt accessions (3): Q9HAB8, Q5VVM2, Q5VVM3

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the second step in the biosynthesis of coenzyme A from vitamin B5, where cysteine is conjugated to 4’-phosphopantothenate to form 4-phosphopantothenoylcysteine. Has a preference for ATP over CTP as a cosubstrate.

Subunit / interactions. Homodimer.

Disease relevance. Cardiomyopathy, dilated, 2C (CMD2C) [MIM:618189] A form of dilated cardiomyopathy, a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD2C is an autosomal recessive form with variable severity and age of onset ranging from 2 to 20 years. Death in infancy or early childhood may occur in severely affected children. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-pantothenate: step 2/5.

Similarity. Belongs to the PPC synthetase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HAB8-1	1	yes
Q9HAB8-2	2

RefSeq proteins (7): NP_001070915, NP_001274435, NP_001274437, NP_001274438, NP_001274439, NP_001274440, NP_078940* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007085	DNA/pantothenate-metab_flavo_C	Domain
IPR035929	CoaB-like_sf	Homologous_superfamily

Pfam: PF04127

Enzyme classification (BRENDA)

• EC 6.3.2.51 — phosphopantothenate-cysteine ligase (ATP) (BRENDA: 9 organisms, 9 substrates, 8 inhibitors, 9 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
(R)-4’-PHOSPHOPANTOTHENATE	0.013–0.057	3
L-CYSTEINE	0.014–0.086	3
CTP	0.156–0.265	2
ATP	0.269	1

Catalyzed reactions (Rhea)

• (R)-4’-phosphopantothenate + L-cysteine + CTP = N-[(R)-4-phosphopantothenoyl]-L-cysteine + CMP + diphosphate + H(+) (RHEA:19397)
• (R)-4’-phosphopantothenate + L-cysteine + ATP = N-[(R)-4-phosphopantothenoyl]-L-cysteine + AMP + diphosphate + H(+) (RHEA:25156)

UniProt features (40 total): helix 17, strand 14, sequence variant 3, turn 2, initiator methionine 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7EDZ	Crystal Structure of human PPCS in complex with P-HoPan and AMPPNP	X-RAY DIFFRACTION	1.95
1P9O	Crystal Structure of Phosphopantothenoylcysteine Synthetase	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAB8-F1	93.94	0.85

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Ligase, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

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.

Post-translational modifications (1)

Type	Positions
N-acetylalanine	2

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: 179 (showing top): FXR_IR1_Q6, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_COENZYME_A_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ACETYL_COA_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, USF_01, chr1p34

GO Biological Process (3): heart process (GO:0003015), acetyl-CoA biosynthetic process (GO:0006085), coenzyme A biosynthetic process (GO:0015937)

GO Molecular Function (7): phosphopantothenate–cysteine ligase activity (GO:0004632), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), ligase activity (GO:0016874)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

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

22 GO namespaces:

Category	Terms
cellular anatomical structure	2
circulatory system process	1
acetyl-CoA metabolic process	1
acyl-CoA biosynthetic process	1
coenzyme A metabolic process	1
sulfur compound biosynthetic process	1
purine-containing compound biosynthetic process	1
nucleoside phosphate biosynthetic process	1
acid-amino acid ligase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
acetyl-CoA biosynthetic process	BP	mutant phenotype
coenzyme A biosynthetic process	BP	direct assay
heart process	BP	mutant phenotype
identical protein binding	MF	physical interaction
phosphopantothenate–cysteine ligase activity	MF	direct assay
protein homodimerization activity	MF	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 750 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPCS	COASY	Q13057	985
PPCS	PANK1	Q8TE04	775
PPCS	PANK2	Q9BZ23	726
PPCS	PANK3	Q9H999	700
PPCS	NUDT8	Q8WV74	659
PPCS	PANK4	Q9NVE7	622
PPCS	DCAKD	Q8WVC6	613
PPCS	SLC25A42	Q86VD7	524
PPCS	NT5C1B	Q96P26	495
PPCS	PPCDC	Q96CD2	493
PPCS	SLC25A16	P16260	435
PPCS	NUDT7	P0C024	434
PPCS	SLC5A6	Q9Y289	419
PPCS	NUDT19	A8MXV4	395
PPCS	SLC25A17	O43808	379

IntAct

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

3 partners by confidence:

Partner	Interaction type	MIscore	Records
CLOCK	physical association	0.400	1
TRMT44	physical association	0.400	1
SCGB2A1	association	0.350	1

BioGRID (69 interactions; top human partners by supporting records): EGFR (Negative Genetic; 2 records), AGO2 (Affinity Capture-RNA), ARL2 (Negative Genetic), BPIFB1 (Affinity Capture-MS), BST1 (Affinity Capture-MS), C5orf46 (Affinity Capture-MS), CCR1 (Affinity Capture-MS), CDC16 (Positive Genetic), CDK7 (Affinity Capture-MS), CKAP5 (Positive Genetic), COA3 (Positive Genetic), COPS2 (Positive Genetic), CTNNBL1 (Positive Genetic), DIS3 (Co-fractionation), DLG3 (Co-fractionation)

Disease & clinical

Genetic variants

Variant evidence for PPCS: 18 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	10
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 139):

Position(s)	Effect	Δscore	Sites
1:42457245–42457246	acceptor_loss	1.0000	2
1:42457070	donor_gain	0.9900
1:42457074–42457075	donor_loss	0.9900	5
1:42457245–42457246	acceptor_loss	0.9900	4
1:42459601–42459602	acceptor_loss	0.9800	6
1:42457351–42457352	donor_loss	0.9700	6
1:42457350	donor_loss	0.9600
1:42457350	donor_loss	0.9400
1:42459600	acceptor_loss	0.9300
1:42457350	donor_loss	0.9200

AlphaMissense

606 missense substitutions predicted likely pathogenic (of 1,986 scored), across 162 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
D183	8	0.978	0.993
F230	8	0.936	0.994
N59	8	0.934	0.996
S61	8	0.920	0.993
F73	8	0.886	0.971
D58	8	0.862	0.950
H303	8	0.849	0.963
F149	7	0.980	0.997
F184	7	0.959	0.993
F82	7	0.950	0.972
K195	7	0.924	0.991
E50	7	0.923	0.972
E233	7	0.902	0.946
F26	7	0.901	0.972
F56	7	0.898	0.988
F226	7	0.883	0.960
N258	7	0.879	0.975
F60	7	0.869	0.975
F90	7	0.806	0.943
W221	7	0.806	0.909

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
Glioblastoma Multiforme (validation)	unfavorable	3.55e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.22e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000115
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000291

Disease associations

OMIM: gene MIM:609853 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
cardiomyopathy, dilated, 2c	Strong	Autosomal recessive	3
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Paediatric or syndromic cardiomyopathy	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (2): cardiomyopathy, dilated, 2c (MONDO:0032592), (MONDO:0015470)

HPO phenotypes

23 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000969	Edema
HP:0001252	Hypotonia
HP:0001522	Death in infancy
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001727	Thromboembolic stroke
HP:0002092	Pulmonary arterial hypertension
HP:0002151	Increased circulating lactate concentration
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy
HP:0003457	EMG abnormality
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003819	Death in childhood
HP:0011463	Childhood onset
HP:0011675	Arrhythmia
HP:0012378	Fatigue
HP:0012664	Reduced left ventricular ejection fraction
HP:0012764	Orthopnea
HP:0025169	Left ventricular systolic dysfunction
HP:0100578	Lipoatrophy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Benzo(a)pyrene	affects methylation	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects methylation	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
T-2 Toxin	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0TH	MRIi028-A	Induced pluripotent stem cell	Male
CVCL_C0HS	HMGUi003-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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