CP

Summary

CP (ceruloplasmin, HGNC:2295) is a protein-coding gene on chromosome 3q24-q25.1, encoding Ceruloplasmin (P00450). Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein.

The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene.

Source: NCBI Gene 1356 — RefSeq curated summary.

At a glance

• Gene–disease (curated): aceruloplasminemia (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,175 total — 90 pathogenic, 55 likely-pathogenic (top 2% of genes corpus-wide)
• GTEx eGene: eQTL in 27 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 48
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.62 (unconstrained)
• MANE Select transcript: NM_000096
• Interaction hub: 1,850 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2295
Approved symbol	CP
Name	ceruloplasmin
Location	3q24-q25.1
Locus type	gene with protein product
Status	Approved
Aliases	AB073614
Ensembl gene	ENSG00000047457
Ensembl biotype	protein_coding
OMIM	117700
Entrez	1356

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 16 protein_coding, 9 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000264613

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 6, TSL 3: 2, TSL 5: 2

ENST00000264613, ENST00000455472, ENST00000460674, ENST00000462336, ENST00000463556, ENST00000471356, ENST00000473296, ENST00000474204, ENST00000479771, ENST00000481169, ENST00000489736, ENST00000490639, ENST00000494544, ENST00000497797, ENST00000497902, ENST00000870686, ENST00000870687, ENST00000870688, ENST00000870689, ENST00000870690, ENST00000979708, ENST00000979709, ENST00000979710, ENST00000979711, ENST00000979712, ENST00001008834, ENST00001108957, ENST00001108958, ENST00001108959, ENST00001116686, ENST00001144862

RefSeq mRNA: 1 — MANE Select: NM_000096 NM_000096

CCDS: CCDS3141

Canonical transcript exons

ENST00000264613 — 19 exons

Exon	Start	End
ENSE00001008197	149221647	149221829
ENSE00001245656	149176250	149176412
ENSE00003463270	149177840	149177979
ENSE00003463548	149179556	149179662
ENSE00003467839	149202102	149202241
ENSE00003470933	149198367	149198578
ENSE00003486135	149172497	149173730
ENSE00003508771	149212451	149212698
ENSE00003530045	149182005	149182133
ENSE00003567271	149210167	149210379
ENSE00003573642	149209211	149209384
ENSE00003585505	149199712	149199864
ENSE00003594625	149186520	149186732
ENSE00003635687	149188052	149188202
ENSE00003639931	149206168	149206339
ENSE00003646391	149207363	149207617
ENSE00003657393	149178415	149178631
ENSE00003667758	149185239	149185446
ENSE00003692951	149183466	149183605

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.68.

FANTOM5 (CAGE): breadth broad, TPM avg 8.0396 / max 2023.4974, expressed in 333 samples.

Highest expression (Bgee): lobe of liver, liver, palpebral conjunctiva, nasal cavity epithelium, olfactory segment of nasal mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 27 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	7.6e-34	-0.94	3:149220559:T:C
Artery Tibial	sqtl	2.4e-11	-1.02	3:149184279:C:G
Cells Cultured fibroblasts	eqtl	8.5e-11	+0.25	3:149222074:T:C
Brain Nucleus accumbens basal ganglia	eqtl	3.9e-09	-0.45	3:149223729:T:C
Nerve Tibial	eqtl	7.5e-09	-0.55	3:149244048:T:C
Artery Tibial	eqtl	1.0e-08	-0.51	3:149211725:A:G
Liver	sqtl	4.2e-07	-0.87	3:149183074:A:C
Esophagus Muscularis	eqtl	1.2e-06	-0.30	3:149222074:T:C
Artery Aorta	sqtl	3.0e-05	-0.93	3:149184279:C:G
Esophagus Mucosa	eqtl	5.3e-05	-0.38	3:149211725:A:G
Colon Sigmoid	eqtl	2.2e-04	-0.27	3:149222074:T:C
Thyroid	eqtl	3.6e-04	-0.34	3:149227648:T:C
Brain Putamen basal ganglia	eqtl	3.9e-04	-0.38	3:149223729:T:C
Heart Atrial Appendage	eqtl	5.7e-04	-0.31	3:149207631:G:A
Nerve Tibial	sqtl	5.9e-04	-0.83	3:149182489:A:G
Brain Anterior cingulate cortex BA24	eqtl	7.2e-04	-0.39	3:149245115:G:A
Brain Cortex	eqtl	1.1e-03	-0.35	3:149223729:T:C
Brain Spinal cord cervical c-1	eqtl	1.3e-03	-0.46	3:149245115:G:A
Thyroid	sqtl	1.3e-03	-0.73	3:149184279:C:G
Colon Transverse	eqtl	1.5e-03	-0.35	3:149222355:A:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
45003	7.0473	285
45005	0.5511	97
45004	0.3220	103
44999	0.0778	23
45006	0.0331	14
45001	0.0083	6

Top tissues by expression

showing 100 of 284 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.68	gold quality
liver	UBERON:0002107	99.34	gold quality
palpebral conjunctiva	UBERON:0001812	99.12	gold quality
nasal cavity epithelium	UBERON:0005384	98.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.59	gold quality
bronchial epithelial cell	CL:0002328	98.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.68	gold quality
nasal cavity mucosa	UBERON:0001826	97.59	gold quality
epithelium of bronchus	UBERON:0002031	97.35	gold quality
bronchus	UBERON:0002185	97.15	gold quality
choroid plexus epithelium	UBERON:0003911	96.24	gold quality
ascending aorta	UBERON:0001496	95.06	gold quality
right coronary artery	UBERON:0001625	95.00	gold quality
thoracic aorta	UBERON:0001515	94.79	gold quality
aorta	UBERON:0000947	94.21	gold quality
tibial artery	UBERON:0007610	94.03	gold quality
popliteal artery	UBERON:0002250	94.01	gold quality
minor salivary gland	UBERON:0001830	93.86	gold quality
calcaneal tendon	UBERON:0003701	93.14	gold quality
colonic epithelium	UBERON:0000397	93.07	gold quality
descending thoracic aorta	UBERON:0002345	92.54	gold quality
rectum	UBERON:0001052	91.12	gold quality
right atrium auricular region	UBERON:0006631	91.00	gold quality
spleen	UBERON:0002106	90.26	gold quality
tendon	UBERON:0000043	90.13	gold quality
epithelium of nasopharynx	UBERON:0001951	89.98	gold quality
mouth mucosa	UBERON:0003729	89.58	gold quality
lymph node	UBERON:0000029	89.16	gold quality
trachea	UBERON:0003126	89.16	gold quality
left coronary artery	UBERON:0001626	88.92	gold quality
cardiac atrium	UBERON:0002081	88.80	gold quality
coronary artery	UBERON:0001621	88.38	gold quality
layer of synovial tissue	UBERON:0007616	88.25	gold quality
mucosa of stomach	UBERON:0001199	88.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.95	gold quality
saliva-secreting gland	UBERON:0001044	87.82	gold quality
skin of leg	UBERON:0001511	87.08	gold quality
left lobe of thyroid gland	UBERON:0001120	86.97	gold quality
tibial nerve	UBERON:0001323	86.96	gold quality
endometrium	UBERON:0001295	86.94	gold quality
buccal mucosa cell	CL:0002336	86.83	gold quality
right lobe of thyroid gland	UBERON:0001119	86.64	gold quality
adenohypophysis	UBERON:0002196	86.58	gold quality
synovial joint	UBERON:0002217	86.52	gold quality
spinal cord	UBERON:0002240	86.04	gold quality
medial globus pallidus	UBERON:0002477	85.99	gold quality
tendon of biceps brachii	UBERON:0008188	85.95	gold quality
small intestine	UBERON:0002108	85.48	gold quality
thyroid gland	UBERON:0002046	85.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.72	gold quality
trabecular bone tissue	UBERON:0002483	83.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.24	gold quality
zone of skin	UBERON:0000014	82.97	gold quality
urethra	UBERON:0000057	82.82	gold quality
transverse colon	UBERON:0001157	82.43	gold quality
decidua	UBERON:0002450	82.22	gold quality
globus pallidus	UBERON:0001875	81.72	gold quality
skin of abdomen	UBERON:0001416	81.49	gold quality
intestine	UBERON:0000160	81.12	gold quality
peritoneum	UBERON:0002358	81.01	gold quality
omental fat pad	UBERON:0010414	81.00	gold quality
islet of Langerhans	UBERON:0000006	80.76	gold quality
pericardium	UBERON:0002407	80.50	gold quality
tonsil	UBERON:0002372	80.45	gold quality
hypothalamus	UBERON:0001898	80.42	gold quality
pituitary gland	UBERON:0000007	80.32	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.08	gold quality
caudate nucleus	UBERON:0001873	80.01	gold quality
substantia nigra	UBERON:0002038	79.95	gold quality
corpus callosum	UBERON:0002336	79.95	gold quality
large intestine	UBERON:0000059	79.87	gold quality
colon	UBERON:0001155	79.86	gold quality
superficial temporal artery	UBERON:0001614	79.83	silver quality
sigmoid colon	UBERON:0001159	79.58	gold quality
right lung	UBERON:0002167	79.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	79.48	gold quality
endocervix	UBERON:0000458	79.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.08	gold quality
duodenum	UBERON:0002114	78.71	gold quality
mammary duct	UBERON:0001765	78.10	gold quality
amygdala	UBERON:0001876	78.00	gold quality
adipose tissue	UBERON:0001013	77.92	gold quality
midbrain	UBERON:0001891	77.88	gold quality
connective tissue	UBERON:0002384	77.88	gold quality
heart	UBERON:0000948	77.70	gold quality
Ammon’s horn	UBERON:0001954	77.61	gold quality
prostate gland	UBERON:0002367	77.61	gold quality
mucosa of sigmoid colon	UBERON:0004993	77.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.15	gold quality
lower esophagus	UBERON:0013473	77.10	gold quality
caput epididymis	UBERON:0004358	77.05	gold quality
putamen	UBERON:0001874	76.83	gold quality
mucosa of transverse colon	UBERON:0004991	76.79	gold quality
skin of hip	UBERON:0001554	76.70	gold quality
metanephros cortex	UBERON:0010533	76.57	gold quality
esophagus	UBERON:0001043	76.55	gold quality
superior surface of tongue	UBERON:0007371	76.49	gold quality
epithelium of mammary gland	UBERON:0003244	76.41	gold quality
right adrenal gland cortex	UBERON:0035827	76.41	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	4924.01
E-GEOD-98556	yes	4573.19
E-GEOD-130148	yes	3779.17
E-HCAD-23	yes	3713.30
E-MTAB-7316	yes	2137.74
E-MTAB-11121	yes	2108.84
E-GEOD-137537	yes	1761.27
E-HCAD-24	yes	1382.54
E-MTAB-10553	yes	738.12
E-MTAB-8142	yes	97.69
E-HCAD-9	yes	54.74
E-CURD-114	yes	50.14
E-MTAB-10287	yes	43.48
E-HCAD-4	yes	23.63
E-MTAB-7249	yes	11.30

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	1750.2	not detected
Retina	tissue	228.4
Choroid plexus	tissue	227.9
Corpus callosum	tissue	91.1
Cervix	tissue	66.0	not detected
Medulla oblongata	tissue	53.9
Spinal cord	tissue	53.6
Midbrain	tissue	47.4
Substantia nigra	tissue	43.5
Periaqueductal gray	tissue	42.2
Thalamus	tissue	35.3
Superior colliculi	tissue	33.2
Pons	tissue	31.0
Pituitary gland	tissue	30.5
Putamen	tissue	26.8
Urinary bladder	tissue	22.3	not detected
Ventral forebrain	tissue	21.2
Spleen	tissue	20.9	not detected
Septum	tissue	20.7
Breast	tissue	19.5	not detected
Tonsil	tissue	18.8	not detected
Hippocampal formation	tissue	18.4
Hypothalamus	tissue	18.3
Lymph node	tissue	17.8	not detected
Rectum	tissue	15.4	not detected
Endometrium 1	tissue	13.9	not detected
Lung	tissue	12.7	not detected
Colon	tissue	12.2	not detected
Olfactory bulb	tissue	12.1
Amygdala	tissue	11.9
Basal ganglia	tissue	10.5	not detected
Cerebral cortex	tissue	10.3	not detected
Retrosplenial cortex	tissue	10.3
Duodenum	tissue	9.2	not detected
Caudate putamen	tissue	8.8
Occipital cortex	tissue	8.7
Somatosensory cortex	tissue	8.4
Insular cortex	tissue	8.3
Frontal cortex	tissue	8.0
Retrosplenial and cingulate cortex	tissue	7.8
Fallopian tube	tissue	7.8	not detected
Tongue	tissue	7.7
Motor cortex	tissue	7.6
Prefrontal cortex	tissue	7.4
Prostate	tissue	7.4	not detected
Temporal cortex	tissue	7.1
Cerebellum	tissue	7.0	not detected
Entorhinal cortex	tissue	6.9
Hippocampus	tissue	6.5	not detected
Small intestine	tissue	5.6	not detected
Adipose tissue	tissue	5.5	not detected
Locus coeruleus	tissue	5.5
Nucleus accumbens	tissue	5.1
Skin 1	tissue	5.0	not detected
Heart muscle	tissue	3.8	not detected
Parathyroid gland	tissue	3.7	not detected
Placenta	tissue	3.2	not detected
Kidney	tissue	3.1	not detected
Esophagus	tissue	3.0	not detected
Vagina	tissue	2.7	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (91.1), Blood vessel (62.0), Ventral spinal cord (53.6), Dorsal spinal cord (46.6), Supraoptic nucleus (44.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPZ, EGR1, FOXC2, FOXO1, GLI1, GLI3, HIF1A, JUN, MBD2, RNF2, SP1, SSRP1

miRNA regulators (miRDB)

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

showing 30 of 77 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4729	99.69	72.18	4233

Functional genomics

gnomAD constraint: pLI 5e-07, LOEUF 0.624, missense Z 1.61 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000264613 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
3:149,173,717–149,198,510	525 / 657.2	0.80	no
3:149,198,511–149,221,792	642 / 627.3	1.02	no
ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• CERULOPLASMIN haS a role in iron uptake rather than release in BT325 cells. (PMID:11681312)
• difference in the molecular structure between human and bovine ceruloplasmin using SDS-PAGE and MALDI-TOF mass spectrometry (PMID:11689010)
• gene coding and flanking regions were sequenced and examined for mutations that might modulate the iron burden of individuals harboring the common mutant hemochromatosis HFE genotype or cause hemochromatosis independent of mutations in the HFE gene (PMID:11783942)
• Studies of the ceruloplasmin-lactoferrin complex (PMID:11908641)
• results show that insulin functions as a bidirectional, condition-dependent regulator of hepatic cell Cp expression; the unique regulation of Cp may reflect its dual roles in inflammation and iron homeostasis (PMID:12029093)
• Carnosine, homocarnosine and anserine significantly inhibited the aggregation of CP induced by peroxyl radicals. (PMID:12132593)
• Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), ceruloplasmin (Cp), and transferrin (Tf) in rheumatoid arthritis. Serum Tf levels were significantly diminished and serum levels of sICAM-1 and Cp were significantly increased. (PMID:12175089)
• the three-copper cluster at the N-terminal-C-terminal interface plays a crucial role in the structural stability of human ceruloplasmin (PMID:12177070)
• elucidation of mechanisms of copper incorporation (PMID:12351628)
• Determination of specific antioxidants like ceruloplasmin in serum may be of value in the early diagnosis of prostate and colon cancer. (PMID:12708132)
• data show that ceruloplasmin stimulates iron release from macrophages under hypoxic conditions by a ferroxidase-dependent mechanism (PMID:12952974)
• Haptoglobin polymorphism was correlated with ceruloplasmin ferroxidase activity in a sample population of unrelated black Jordanians and activity is both haptoglobin type and concentration dependent. (PMID:15103512)
• Urinary levels are increaed in normoalbuminuric type 2 diabetic patients. (PMID:15111541)
• 5 new missense (I63T, P477L, T551I, R793H, T841R) & 3 new silent variations (g:9230/C->A, g:42221/C->T, g:4400/T->C) were found. Cp colocalized with Fe in Lewy bodies, suggesting a role in pathogenesis of Parkinson disease. (PMID:15557511)
• REVIEW: mechanism for the involvement of ceruloplasmin in cardiovascular disease (PMID:15668644)
• hypoxia-inducible factor (HIF)-1 has a role in ceruloplasmin regulation (PMID:15741220)
• Cp polypeptides with molecular weight of nearly 30 kDa were found in mitochondria of HuTu 80 cells (PMID:15752613)
• altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in Parkinson’s disease (PMID:16150804)
• Increased levels in urine predicts development of microalbuminuria in type 2 diabetes. (PMID:16373913)
• results showed that exposure of CP to methylglyoxal led to protein aggregation and that aggregation of CP induced the inactivation of feroxidase and the release of copper ions (PMID:16756764)
• Results describe the biochemical features of wild-type and mutant GPI-anchored ceruloplasmin. (PMID:16775387)
• A biochemical analysis of the patients’ serum and a biogenesis study of G969S mutant ceruloplasmin using mammalian cell culture system resulted in the synthesis and secretion of only apoceruloplasmin without any ferroxidase activity. (PMID:16831606)
• In a Chinese woman who had diabetes mellitus, undetectable ceruloplasmin, hand tremor, neck dystonia, and cognitive disturbances, genetic analyses revealed a novel homozygous mutation (848G > C or W283S) in exon 5 in the ceruloplasmin gene. (PMID:17013908)
• ceruloplasmin gene is regulated by activator protein-1 site in the gene by redox active copper. (PMID:17032174)
• CP levels wefre determined in children with Henoch-Schonlein purpura. (PMID:17404760)
• describe a study of the conformation of the human lactoferrin/ceruloplasmin complex in solution using small angle X-ray scattering (PMID:17597152)
• The truncated mutant containing Cys-881 was able to pass through the ER and was secreted, while the truncated mutant protein without Cys-881 appeared to accumulate in the ER thus leading to ER stress and eventually resulting in cell death. (PMID:17637479)
• In vitro equilibrium unfolding of CP involves intermediates and the copper ions are removed in stages. (PMID:17661447)
• With regard to septic liver dysfunction, signs of cholestasis were mostly reflected in greater increases in Cp (PMID:17688883)
• In contrast, apo-CP unfolds rapidly: the denatured state is reached in <2 days at 37 degrees C. (PMID:17965133)
• The involvement of lymphocyte-derived CP on host defense processes via its anti/prooxidant properties is proposed, giving further support for a close functional interaction between the immune system and the Fe metabolism. (PMID:17991445)
• stable complex between these Cp and Hp and Tf does not occur under the experimental conditions used (PMID:18022819)
• In the cerebrospinal fluid of Alzheimer’s disease patients the decrease of active CP, associated with the increase in the pool of copper not sequestered by this protein, may play a role in the neurodegenerative process (PMID:18060472)
• Measurement of Cp separated by the present method could be useful for the diagnosis of ITP in the presence of thrombocytopenia and a non- or low-inflammatory state (PMID:18187043)
• We report two siblings with markedly different phenotypes carrying a novel mutation: a homozygous deletion of two nucleotides (1257-1258 TT del) causing the premature stop of the Cp protein translation (Y401X). (PMID:18200628)
• Multiple motor system dysfunction associated with a heterozygous ceruloplasmin gene mutation. (PMID:18293024)
• Results describe the activity of ferroxidase, SOD1, and cofactors in CSF of patients with Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, or amyotrophic lateral sclerosis. (PMID:18307039)
• Investigated of brain iron levels in two asymptomatic young adult carriers with heterozygous mutations of Cp gene by using T2*-weighted MR images. (PMID:18311828)
• Ceruloplasmin is a better predictor of the long-term prognosis compared with fibrinogen, CRP, and IL-6 in patients with severe unstable angina. (PMID:18388036)
• there is an increase in ceruloplasmin levels in placental tissue in preeclampsia compared to preterm and normal controls (PMID:18679377)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cp	ENSDARG00000010312
mus_musculus	Cp	ENSMUSG00000003617
rattus_norvegicus	Cp	ENSRNOG00000011913

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88476) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 40 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased liver iron level	5
decreased circulating iron level	4
abnormal lipid homeostasis	2
abnormal brain iron level	2
abnormal hepatocyte morphology	1
abnormal fourth ventricle morphology	1
abnormal Purkinje cell morphology	1
abnormal cerebellar granule layer morphology	1
demyelination	1
decreased motor neuron number	1
abnormal locomotor behavior	1
impaired coordination	1
abnormal gait	1
abnormal iron level	1
abnormal sensory capabilities/reflexes/nociception	1
abnormal astrocyte morphology	1
decreased mean corpuscular volume	1
microcytic anemia	1
increased heart weight	1
decreased hemoglobin content	1
abnormal neuron morphology	1
hypoalgesia	1
abnormal liver copper level	1
neuron degeneration	1
abnormal locomotor activation	1

+15 more (showing top 25).

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
Oxyuranus microlepidotus	Q58L90	97.7%	Diamond
Oxyuranus scutellatus	Q58L91	97.7%	Diamond
Pseudonaja textilis	Q7SZN0	96.9%	Diamond
Ovis aries	Q9XT27	84.9%	Diamond
Bos taurus	Q28107	79.6%	Diamond
Sus scrofa	Q9GLP1	79.6%	Diamond
Canis lupus familiaris	O18806	77.1%	Diamond
Acropora millepora	B3EWZ9	50.4%	Diamond
Mycobacterium tuberculosis H37Rv	I6WZK7	47.7%	Diamond
Pestalotiopsis fici W106-1	W3X7K0	43.8%	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
GYG1	protein-coding	2992
HLTF	protein-coding	6596
HPS3	protein-coding	84343
HLTF-AS1	ncRNA	100873945
TM4SF18	protein-coding	116441
TM4SF18-AS1	ncRNA	128193290

Protein

Protein identifiers

Ceruloplasmin — P00450 (reviewed: P00450)

Alternative names: Cuproxidase ceruloplasmin, Ferroxidase ceruloplasmin, Glutathione peroxidase ceruloplasmin, Glutathione-dependent peroxiredoxin ceruloplasmin

All UniProt accessions (5): D6RE86, E9PFZ2, H7C5N5, H7C5R1, P00450

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Copper ions provide a large number of enzymatic activites. Oxidizes highly toxic ferrous ions to the ferric state for further incorporation onto apo-transferrins, catalyzes Cu(+) oxidation and promotes the oxidation of biogenic amines such as norepinephrin and serotonin. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. Has glutathione peroxidase-like activity, can remove both hydrogen peroxide and lipid hydroperoxide in the presence of thiols. Acts as an inhibitor of the peroxidase activity of MPO. Also shows NO-oxidase and NO2 synthase activities that determine endocrine NO homeostasis.

Subunit / interactions. Found in a complex with MPO and LTF; interacts directly with MPO and LTF, which allows Fe(3+) incorporation into LTF, activation of CP ferroxidase activity and protection of CP antioxidant properties by MPO.

Subcellular location. Secreted.

Tissue specificity. Expressed by the liver and secreted in plasma.

Disease relevance. Aceruloplasminemia (ACEP) [MIM:604290] An autosomal recessive disorder of iron metabolism characterized by iron accumulation in the brain as well as visceral organs. Clinical features consist of the triad of retinal degeneration, diabetes mellitus and neurological disturbances. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 6 Cu(2+) cations per monomer.

Similarity. Belongs to the multicopper oxidase family.

RefSeq proteins (1): NP_000087* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001117	Cu-oxidase_2nd	Domain
IPR002355	Cu_oxidase_Cu_BS	Binding_site
IPR008972	Cupredoxin	Homologous_superfamily
IPR011706	Cu-oxidase_C	Domain
IPR011707	Cu-oxidase-like_N	Domain
IPR033138	Cu_oxidase_CS	Conserved_site
IPR045087	Cu-oxidase_fam	Family
IPR048236	Ceruloplasmin-like_CuRO_5	Domain

Pfam: PF00394, PF07731, PF07732

Enzyme classification (BRENDA)

• EC 1.16.3.1 — ferroxidase (BRENDA: 52 organisms, 108 substrates, 62 inhibitors, 161 Km, 41 kcat entries)
• EC 1.16.3.4 — cuproxidase (BRENDA: 8 organisms, 18 substrates, 2 inhibitors, 20 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

60 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FE2+	0.0006–14.1	29
HYDROQUINONE	0.018–30.5	22
P-PHENYLENEDIAMINE	0.005–1.19	18
FE(II)	0.0006–3.994	14
O2	0.0011–0.0632	10
CU+	—	8
O-DIANISIDINE	0.12–0.76	5
CU2+	0.163–82	5
NADH	0.14–0.23	4
FE2+	0.0526–0.129	4
N,N’-DIMETHYL-P-PHENYLENEDIAMINE	0.06–0.164	3
[CU(I)(MECN4)]PF6+	0.0344–0.427	3
L-EPINEPHRINE	0.0026–5.8	2
O-PHENYLENEDIAMINE	0.0029–4.15	2
2-CHLORO-P-PHENYLENEDIAMINE	0.241	1

Catalyzed reactions (Rhea)

• 4 Fe(2+) + O2 + 4 H(+) = 4 Fe(3+) + 2 H2O (RHEA:11148)
• 2 glutathione + H2O2 = glutathione disulfide + 2 H2O (RHEA:16833)
• 4 Cu(+) + O2 + 4 H(+) = 4 Cu(2+) + 2 H2O (RHEA:30083)
• a hydroperoxide + 2 glutathione = an alcohol + glutathione disulfide + H2O (RHEA:62632)
• 4 nitric oxide + O2 + 2 H2O = 4 nitrite + 4 H(+) (RHEA:78539)

UniProt features (176 total): strand 68, binding site 40, helix 33, sequence variant 7, turn 6, domain 6, glycosylation site 6, disulfide bond 5, signal peptide 1, chain 1, modified residue 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
4ENZ	Structure of human ceruloplasmin at 2.6 A resolution	X-RAY DIFFRACTION	2.6
2J5W	Ceruloplasmin revisited: structural and functional roles of various metal cation binding …	X-RAY DIFFRACTION	2.8
1KCW	X-RAY CRYSTAL STRUCTURE OF HUMAN CERULOPLASMIN AT 3.0 ANGSTROMS	X-RAY DIFFRACTION	3
4EJX	Structure of ceruloplasmin-myeloperoxidase complex	X-RAY DIFFRACTION	4.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00450-F1	93.79	0.90

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Transporters, Accessory Factors Involved in Transport, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, Candidate cardiovascular disease genes, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

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
699	nucleophile; for glutathione peroxidase activity

Ligand- & substrate-binding residues (40)

Position	Role
64	Na(+)
67	Na(+)
120	Cu(2+)
120	O2
122	Cu(2+)
128	Ca(2+)
143	Ca(2+)
146	Ca(2+)
147	Ca(2+)
180	Cu(2+)
180	O2
182	Cu(2+)
256	Na(+)
295	Cu(2+)
338	Cu(2+)
343	Cu(2+)
408	Na(+)
417	Na(+)
420	Na(+)
617	Na(+)
656	Cu(2+)
699	Cu(2+)
704	Cu(2+)
709	Cu(2+)
767	Na(+)
776	Na(+)
779	Na(+)
955	Na(+)
994	Cu(2+)
997	Cu(2+)
997	O2
999	Cu(2+)
999	O2
1039	Cu(2+)
1040	Cu(2+)
1041	Cu(2+)
1041	O2
1045	Cu(2+)
1050	Cu(2+)
55	Na(+)

Post-translational modifications (1)

Type	Positions
Phosphoserine	722

Disulfide bonds (5)

Type	Positions
Disulfide bond	174–200, 276–357, 534–560, 637–718, 874–900

Glycosylation sites (6)

Type	Positions
N-linked (glcnac…) (complex) asparagine	138, 358, 397, 762
N-linked (glcnac…) asparagine	588, 926

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 14; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

14 pathways:

ID	Pathway	Evidence
R-HSA-5619060	Defective CP causes aceruloplasminemia (ACERULOP) ⚕	curated
R-HSA-5619049	Defective SLC40A1 causes hemochromatosis 4 (HFE4) (macrophages) ⚕	curated
R-HSA-917937	Iron uptake and transport	curated
R-HSA-425410	Metal ion SLC transporters	curated
R-HSA-8957275	Post-translational protein phosphorylation	curated
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5619115	Disorders of transmembrane transporters ⚕	—
R-HSA-5619102	SLC transporter disorders ⚕	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-425366		—
R-HSA-425407	SLC-mediated transmembrane transport	—
R-HSA-382551	Transport of small molecules	—

MSigDB gene sets: 372 (showing top): MODULE_93, HNF3ALPHA_Q6, HARRIS_HYPOXIA, GOCC_VACUOLAR_MEMBRANE, MODULE_418, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN

GO Biological Process (4): intracellular copper ion homeostasis (GO:0006878), intracellular iron ion homeostasis (GO:0006879), negative regulation of translation (GO:0017148), cellular oxidant detoxification (GO:0098869)

GO Molecular Function (10): ferroxidase activity (GO:0004322), glutathione peroxidase activity (GO:0004602), copper ion binding (GO:0005507), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on metal ions, oxygen as acceptor (GO:0016724), peroxidase inhibitor activity (GO:0036479), phospholipid-hydroperoxide glutathione peroxidase activity (GO:0047066), protein-folding chaperone binding (GO:0051087), oxidoreductase activity, acting on metal ions (GO:0016722), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), lysosomal membrane (GO:0005765), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), blood microparticle (GO:0072562)

Reactome top-level categories

7 top-level categories:

Category	Pathways
Metabolism of proteins	2
SLC transporter disorders	2
Transport of small molecules	2
SLC-mediated transmembrane transport	1
Post-translational protein modification	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

26 GO namespaces:

Category	Terms
peroxidase activity	3
intracellular monoatomic cation homeostasis	2
cellular anatomical structure	2
copper ion homeostasis	1
inorganic ion homeostasis	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
cellular detoxification	1
oxidoreductase activity, acting on metal ions, oxygen as acceptor	1
transition metal ion binding	1
catalytic activity	1
oxidoreductase activity, acting on metal ions	1
enzyme inhibitor activity	1
protein binding	1
oxidoreductase activity	1
cation binding	1
lysosome	1
lytic vacuole membrane	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
extracellular vesicle	1
extracellular region	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
intracellular copper ion homeostasis	BP	direct assay
intracellular iron ion homeostasis	BP	direct assay
blood microparticle	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay
lysosomal membrane	CC	high-throughput assay
ferroxidase activity	MF	direct assay
glutathione peroxidase activity	MF	direct assay
oxidoreductase activity, acting on metal ions, oxygen as acceptor	MF	direct assay
phospholipid-hydroperoxide glutathione peroxidase activity	MF	direct assay
protein-folding chaperone binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,850 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CP	ATP7B	P35670	961
CP	ATP7A	Q04656	902
CP	MRPL13	Q9BYD1	873
CP	HP	P00737	869
CP	ORM2	P19652	845
CP	ORM1	P02763	842
CP	SERPINA1	P01009	795
CP	H3BSS0	H3BSS0	774
CP	ALB	P02768	740
CP	RPL13A	P40429	739
CP	HFE	Q30201	731
CP	A2M	P01023	730
CP	ATOX1	O00244	722
CP	ADAM8	P78325	711
CP	HPX	P02790	706

IntAct

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

4 partners by confidence:

Partner	Interaction type	MIscore	Records
SLC40A1	physical association	0.400	1
BTRC	physical association	0.370	1
GDPD1	association	0.350	2
DDHD2	association	0.350	1

BioGRID (69 interactions; top human partners by supporting records): GDPD1 (Affinity Capture-MS; 3 records), DDX31 (Affinity Capture-MS; 2 records), SNX27 (Affinity Capture-MS; 2 records), ACBD3 (Co-fractionation), AGPAT1 (Affinity Capture-MS), AGR2 (Proximity Label-MS), APOA1 (Affinity Capture-MS), BTRC (Two-hybrid), C6 (Cross-Linking-MS (XL-MS)), CCR1 (Affinity Capture-MS), CIR1 (Affinity Capture-MS), CLU (Affinity Capture-MS), DDHD2 (Affinity Capture-MS), DNMT1 (Affinity Capture-MS), DYNLT1 (Proximity Label-MS)

SIGNOR signaling

showing 2 of 5 signaling interactions:

A	Effect	B	Mechanism
SHH	down-regulates	CP	binding
CP	down-regulates	SMO	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
CP-LTF-MPO complex	3	LTF, MPO, CP
CP-LTF complex	2	CP, LTF
CP-MPO complex	2	CP, MPO

Disease & clinical

Genetic variants

Variant evidence for CP: 1,175 ClinVar records (145 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

1,175 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	90
Likely pathogenic	55
Uncertain significance	450
Likely benign	354
Benign	99

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 145 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
930923	NM_032383.5(HPS3):c.2464C>T (p.Arg822Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
42124	NM_000096.4(CP):c.2701C>T (p.Arg901Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
488150	NM_000096.4(CP):c.1208+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	3
627049	NM_032383.5(HPS3):c.2814dup (p.Leu939fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
871317	NM_000096.4(CP):c.2527_2528del (p.Ser843fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
987426	NM_032383.5(HPS3):c.2736del (p.Glu913fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2630109	NM_000096.4(CP):c.1991_1992del (p.Thr664fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3588688	NM_032383.5(HPS3):c.2805G>A (p.Trp935Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3629557	NM_000096.4(CP):c.2122G>A (p.Gly708Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
521552	NM_000096.4(CP):c.583G>A (p.Gly195Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	6
128844	NM_000096.4(CP):c.656T>A (p.Val219Glu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
431112	NM_000096.4(CP):c.2879-1G>T	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2676079	NM_032383.5(HPS3):c.2808G>A (p.Trp936Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2676090	NM_032383.5(HPS3):c.2440C>T (p.Gln814Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
17559	NM_000096.4(CP):c.3019-1G>A	Pathogenic	criteria provided, single submitter	3

Per-variant reference — Sugi Variant

Explore CP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 37 predictions of 1,611):

Position(s)	Effect	Δscore	Sites
3:149177838–149177839	donor_loss	1.0000	5
3:149177980–149177981	acceptor_loss	1.0000	5
3:149182003–149182004	donor_loss	1.0000	3
3:149183607	acceptor_gain	1.0000
3:149188047	donor_loss	1.0000
3:149188050–149188051	donor_loss	1.0000	5
3:149202100–149202101	donor_loss	1.0000	5
3:149206166–149206167	donor_loss	1.0000	5
3:149206170	donor_gain	1.0000
3:149206340–149206341	acceptor_loss	1.0000	6

AlphaMissense

1,850 missense substitutions predicted likely pathogenic (of 7,090 scored), across 489 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
M1050	9	0.893	0.966
M709	9	0.841	0.947
N111	8	0.942	0.991
D888	8	0.936	0.981
H999	8	0.934	0.971
H1041	8	0.927	0.966
H1039	8	0.926	0.960
D188	8	0.925	0.993
H1045	8	0.923	0.967
N826	8	0.919	0.984
H997	8	0.912	0.971
H180	8	0.910	0.977
H994	8	0.909	0.979
H120	8	0.908	0.987
H182	8	0.906	0.954
H122	8	0.901	0.967
D1014	8	0.888	0.956
H295	8	0.886	0.975
D992	8	0.876	0.945
H704	8	0.873	0.945

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Liver Hepatocellular Carcinoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (validation)	unfavorable	0.000617

Disease associations

OMIM: gene MIM:117700 | disease phenotypes: MIM:614072, MIM:203300, MIM:604290, MIM:234200

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
aceruloplasminemia	Definitive	Autosomal recessive	4
disorder of iron metabolism and transport	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
aceruloplasminemia	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (16 panels, 16 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

16 panels:

Panel	Rating
Adult-onset neurological disorders	green
Ataxia and cerebellar anomalies - childhood onset	green
Dystonia, chorea or related movement disorder, adult onset	green
Early onset dystonia	green
Hereditary ataxia	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hereditary ataxia, adult onset	green
Hypotonic infant	green
Iron metabolism disorders - NOT common HFE mutations	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Neurodegenerative disorders, adult onset	green
Paediatric disorders	green
Structural basal ganglia disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (5): Hermansky-Pudlak syndrome 3 (MONDO:0013555), Hermansky-Pudlak syndrome (MONDO:0019312), aceruloplasminemia (MONDO:0011426), neurodegeneration with brain iron accumulation (MONDO:0018307), disorder of iron metabolism and transport (MONDO:0017763)

Orphanet (4): Hermansky-Pudlak syndrome due to BLOC-2 deficiency (Orphanet:231512), Hermansky-Pudlak syndrome (Orphanet:79430), Aceruloplasminemia (Orphanet:48818), Neurodegeneration with brain iron accumulation (Orphanet:385)

HPO phenotypes

48 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000273	Facial grimacing
HP:0000473	Torticollis
HP:0000546	Retinal degeneration
HP:0000608	Macular degeneration
HP:0000639	Nystagmus
HP:0000643	Blepharospasm
HP:0000707	Abnormality of the nervous system
HP:0000726	Dementia
HP:0000741	Apathy
HP:0000819	Diabetes mellitus
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001635	Congestive heart failure
HP:0001903	Anemia
HP:0002063	Rigidity
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002072	Chorea
HP:0002168	Scanning speech
HP:0002304	Akinesia
HP:0002354	Memory impairment
HP:0002396	Cogwheel rigidity
HP:0003281	Increased circulating ferritin concentration
HP:0003581	Adult onset
HP:0004305	Involuntary movements
HP:0004840	Hypochromic microcytic anemia
HP:0005505	Refractory anemia
HP:0007703	Abnormal retinal pigmentation
HP:0010837	Decreased circulating ceruloplasmin concentration
HP:0010994	Abnormal corpus striatum morphology
HP:0011967	Decreased circulating copper concentration
HP:0012090	Abnormal pancreas morphology
HP:0012179	Craniofacial dystonia
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0012465	Elevated hepatic iron concentration
HP:0012675	Iron accumulation in brain
HP:0012696	Abnormal thalamic MRI signal intensity
HP:0025498	Aceruloplasminemia
HP:0040303	Decreased circulating iron concentration
HP:0100321	Abnormal dentate nucleus morphology
HP:0100543	Cognitive impairment

GWAS associations

1 associations:

Study	Trait	p-value
GCST001521_29	Subcutaneous adipose tissue	1e-6

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D022861	Hermanski-Pudlak Syndrome	C11.270.040.545.400; C15.378.100.100.515; C15.378.100.685.400; C15.378.140.735.400; C15.378.463.735.400; C16.320.099.515; C16.320.290.040.100.400; C16.320.565.100.102.100.400; C16.320.850.080.100.400; C17.800.621.440.102.100.400; C17.800.827.080.100.400; C18.452.648.100.102.100.400
C538421	Neurodegeneration with brain iron accumulation (NBIA) *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

104 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Copper	affects binding, decreases activity, decreases expression, increases activity, increases expression (+1 more)	9
Iron	affects reaction, increases activity, decreases export, affects binding, increases oxidation (+1 more)	5
Lead	increases expression, affects binding, affects expression, decreases activity	4
Oxygen	affects reaction, increases activity, increases expression	4
Benzo(a)pyrene	increases methylation, affects cotreatment, affects expression, increases expression	3
Calcitriol	increases expression	3
Tretinoin	increases expression	3
bisphenol A	affects expression, decreases expression, increases methylation	2
sodium arsenite	decreases expression, increases expression	2
Zoledronic Acid	increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	increases abundance, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Hydrogen Peroxide	decreases expression, decreases secretion, increases degradation	2
Smoke	decreases nitrosation, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	decreases expression	2
Copper Sulfate	affects cotreatment, increases expression, decreases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
dicrotophos	decreases expression	1
bathocuproine	affects binding, decreases reaction, increases reaction	1
chloroacetaldehyde	decreases expression	1
propionaldehyde	decreases expression	1
chlortoluron	decreases expression	1
fluoranthene	affects cotreatment, affects expression	1
potassium persulfate	increases expression	1
zinc chloride	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C1XX	IBMS-iPSC-077-01	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

54 trials:

NCT	Phase	Status	Title
NCT00202397	Phase 2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT02540655	Phase 2	COMPLETED	Efficacy and Safety Study of Stemchymal® in Polyglutamine Spinocerebellar Ataxia
NCT04193592	Phase 2	UNKNOWN	Efficacy and Safety of Pirfenidone Treatment in HPS-ILD
NCT05157802	Phase 1	UNKNOWN	Promoting Physical Activity Engagement for People With Early-stage Cerebellar Ataxia
NCT01104649	Phase 2/3	COMPLETED	Efficacy of Riluzole in Hereditary Cerebellar Ataxia
NCT01649687	Phase 1/2	COMPLETED	Treatment of Cerebellar Ataxia With Mesenchymal Stem Cells
NCT01958177	Phase 1/2	UNKNOWN	Clinical Study to Evaluate the Safety and Efficacy BMMNC in Cerebellar Ataxia
NCT04184453	Early Phase 1	UNKNOWN	Clinical Curative Effect Evaluation Study of Treatment of Oral Deferiprone Tablets in Aceruloplasminaemia Patients
NCT00006492	Not specified	COMPLETED	Gluten-Free Diet in Patients With Gluten Sensitivity and Cerebellar Ataxia
NCT01307176	Not specified	COMPLETED	Exercise Training Program for Cerebellar Ataxia
NCT02887703	Not specified	COMPLETED	Augmenting Balance in Individuals With Cerebellar Ataxias
NCT02900508	Not specified	COMPLETED	Virtual Reality-based Training in Cerebellar Ataxia
NCT02903290	Not specified	COMPLETED	Longitudinal Monitoring of Energy Expenditure, Dynamic Stability and Fatigue During Gait in Patients With Cerebellar Ataxia Gene
NCT03120013	Not specified	COMPLETED	Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia
NCT03213106	Not specified	UNKNOWN	Cerebellar Non-invasive Stimulation in Ataxias
NCT03269201	Not specified	UNKNOWN	Brain Network Activation in Patients With Movement Disorders
NCT03341416	Not specified	UNKNOWN	Effects of Deep Brain Stimulation of the Dentate Nucleus on Cerebellar Ataxia
NCT03879018	Not specified	RECRUITING	Retraining Reaching in Cerebellar Ataxia
NCT03972202	Not specified	ACTIVE_NOT_RECRUITING	The Role of Cerebellum in Speech
NCT04010214	Not specified	RECRUITING	A Registered Cohort Study on Cerebellar Ataxia in the Organization in South-East China for Cerebellar Ataxia Research (OSCCAR)
NCT04039048	Not specified	UNKNOWN	Effect of ctDCS During Balance Training on Cerebellar Ataxia
NCT04054726	Not specified	UNKNOWN	A Study on Cerebello-Spinal tPCS in Ataxia
NCT04529252	Not specified	ACTIVE_NOT_RECRUITING	Investigating the Genetic and Phenotypic Presentation of Ataxia and Nucleotide Repeat Diseases
NCT04648501	Not specified	COMPLETED	Dual Task Training for Cerebellar Ataxia
NCT04703595	Not specified	COMPLETED	Chronic Cough and CANVAS (Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome)
NCT04750850	Not specified	COMPLETED	Core Stability Exercises and Hereditary Ataxia
NCT04790981	Not specified	COMPLETED	Effect of Motor Imagery Training on Ataxic Children After Medulloblastoma Resection
NCT05002218	Not specified	COMPLETED	Training in Ataxia - Individuals With Degenerative Cerebellar Diseases
NCT05024240	Not specified	UNKNOWN	Interaction of the Cognitive and Sensory-cognitive Tasks With Postural Stability in Individuals With Stability Disorders
NCT05095870	Not specified	COMPLETED	Evaluation of the Peripheral Nerve Ultrasound as a Diagnostic Tool in CANVAS Neuropathies
NCT05132647	Not specified	UNKNOWN	Circular Timed Up and Go (cTUG) for Ataxia: Development and Validation
NCT05278091	Not specified	COMPLETED	Evaluation of the Diagnostic Value of Video-oculography in CANVAS Neuronopathies
NCT05351255	Not specified	ACTIVE_NOT_RECRUITING	Motor Learning After Cerebellar Damage: The Role of the Primary Motor Cortex
NCT05436262	Not specified	COMPLETED	Using Real-time fMRI Neurofeedback and Motor Imagery to Enhance Motor Timing and Precision in Cerebellar Ataxia
NCT05443906	Not specified	RECRUITING	Home Exercise for Individuals With Neurodegenerative Disease
NCT05522374	Not specified	RECRUITING	TIRCON International NBIA Registry
NCT05625620	Not specified	UNKNOWN	Cerebellar-spinal Transcranial Pulsed Current Stimulation (tPCS) for Treatment of Neurodegenerative Ataxia
NCT05992207	Not specified	COMPLETED	Utilization of Motor Imagery Training for Improvement of Balance of Ataxic Children After Medulloblastoma Resection
NCT06152133	Not specified	COMPLETED	Telerehabilitation, Core Stability Exercises and Hereditary Ataxia (TRCore-ataxia)
NCT06450457	Not specified	COMPLETED	Effects of High Intensity Stepping Training on Gait in Patients With Ataxia
NCT06573866	Not specified	ACTIVE_NOT_RECRUITING	Enhancement of Quality of Work And Life
NCT06817707	Not specified	RECRUITING	Evaluation of Urinary Dysfunction in CANVAS Patients
NCT07211490	Not specified	NOT_YET_RECRUITING	rTMS for Cerebellar Ataxia in Children
NCT07352085	Not specified	COMPLETED	Exoskeleton-assisted Neurorehabilitation
NCT07642856	Not specified	RECRUITING	Individualized Neuro-Modulation Paired With Cerebellar Therapy
NCT00467831	Phase 1/2	TERMINATED	Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT00001456	Not specified	RECRUITING	Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
NCT00084305	Not specified	ACTIVE_NOT_RECRUITING	Analysis of Specimens From Individuals With Pulmonary Fibrosis
NCT01417520	Not specified	COMPLETED	Clinical and Pathophysiological Investigations Into Erdheim Chester Disease
NCT02368340	Not specified	COMPLETED	A Longitudinal Study of Hermansky-Pudlak Syndrome Pulmonary Fibrosis
NCT02587858	Not specified	UNKNOWN	NBIAready: Online Collection of Natural History Patient-reported Outcome Measures
NCT05615571	Not specified	COMPLETED	Testing of NBIA Genes: Analysis of Genetic Heterogeneity and Validation of Mitochondrial Markers for Assessing Causality of Sequence Variants.
NCT05696912	Not specified	UNKNOWN	Functional Tests to Resolve Unsolved Rare Diseases. Rares.
NCT06596746	Not specified	RECRUITING	Neurodegenerative Diseases Progression Markers (MARKERS-NDD)