CUBN

Summary

CUBN (cubilin, HGNC:2548) is a protein-coding gene on chromosome 10p13, encoding Cubilin (O60494). Endocytic receptor which plays a role in lipoprotein, vitamin and iron metabolism by facilitating their uptake.

Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubulin is located within the epithelium of intestine and kidney. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia.

Source: NCBI Gene 8029 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Imerslund-Grasbeck syndrome type 1 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 50
• Clinical variants (ClinVar): 2,582 total — 63 pathogenic, 110 likely-pathogenic
• Phenotypes (HPO): 40
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001081

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2548
Approved symbol	CUBN
Name	cubilin
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	IFCR, gp280
Ensembl gene	ENSG00000107611
Ensembl biotype	protein_coding
OMIM	602997
Entrez	8029

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding_CDS_not_defined, 2 retained_intron, 2 protein_coding

ENST00000377823, ENST00000377833, ENST00000433666, ENST00000438254, ENST00000648092, ENST00000649135, ENST00000649933

RefSeq mRNA: 1 — MANE Select: NM_001081 NM_001081

CCDS: CCDS7113

Canonical transcript exons

ENST00000377833 — 67 exons

Exon	Start	End
ENSE00000503895	16888417	16888566
ENSE00000614424	16876897	16877097
ENSE00000614425	16874374	16874503
ENSE00000614426	16869636	16869853
ENSE00000692563	16890371	16890527
ENSE00000692707	17088164	17088345
ENSE00000692708	17100005	17100239
ENSE00000692710	17103125	17103237
ENSE00000692716	17109640	17109735
ENSE00000692719	17114027	17114189
ENSE00000692724	17123588	17123689
ENSE00000692728	17129121	17129250
ENSE00000815979	17041033	17041220
ENSE00000815992	17127829	17127924
ENSE00000925926	16831252	16831417
ENSE00000925927	16835014	16835195
ENSE00000925929	16840330	16840535
ENSE00000925931	16898996	16899183
ENSE00000925932	16900625	16900850
ENSE00000925933	16901338	16901459
ENSE00000925934	16903966	16904115
ENSE00000925944	17104419	17104605
ENSE00000925947	17105457	17105575
ENSE00000925951	17110919	17111050
ENSE00000925957	17115471	17115597
ENSE00000925961	17122795	17122898
ENSE00000985435	17126761	17126799
ENSE00000985437	17084271	17084461
ENSE00000985438	17071827	17071971
ENSE00000985439	17071426	17071604
ENSE00000985440	17068605	17068770
ENSE00000985441	17068064	17068280
ENSE00000985442	17065508	17065638
ENSE00000985443	17047414	17047603
ENSE00000985444	17045934	17046094
ENSE00000985445	17045007	17045188
ENSE00000985447	17019833	17019983
ENSE00000985448	16990334	16990515
ENSE00000985449	16984105	16984279
ENSE00000985450	16982484	16982653
ENSE00000985451	16954389	16954548
ENSE00000985452	16952276	16952389
ENSE00000985453	16950001	16950111
ENSE00000985454	16948478	16948606
ENSE00000985456	16940032	16940237
ENSE00000985457	16938963	16939147
ENSE00000985458	16937592	16937784
ENSE00000985459	16933087	16933284
ENSE00000985460	16928157	16928303
ENSE00000985463	16851235	16851443
ENSE00001098716	16925584	16925774
ENSE00001164027	16836235	16836382
ENSE00001164296	17085597	17085759
ENSE00001192896	16947235	16947367
ENSE00001283594	17043827	17043983
ENSE00001475273	16823966	16825082
ENSE00001475420	17129644	17129811
ENSE00001635703	16915821	16916030
ENSE00001651724	16913811	16913992
ENSE00001715158	16915032	16915172
ENSE00001725876	16918622	16918800
ENSE00001738727	16840885	16841047
ENSE00001745825	16919963	16920137
ENSE00001795343	16907508	16907679
ENSE00001796817	16906203	16906409
ENSE00001799112	16925241	16925424
ENSE00001800480	16828805	16829040

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 95.36.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0096 / max 255.2028, expressed in 221 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108481	0.5189	63
108472	0.2231	121
108471	0.0803	24
108482	0.0750	25
205736	0.0401	16
108484	0.0399	22
108485	0.0172	7
108483	0.0151	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult organism	UBERON:0007023	95.36	gold quality
nephron tubule	UBERON:0001231	94.27	gold quality
kidney epithelium	UBERON:0004819	92.57	gold quality
adult mammalian kidney	UBERON:0000082	91.78	gold quality
kidney	UBERON:0002113	90.84	gold quality
renal glomerulus	UBERON:0000074	89.24	gold quality
renal medulla	UBERON:0000362	89.11	gold quality
metanephric glomerulus	UBERON:0004736	88.59	gold quality
cortex of kidney	UBERON:0001225	86.35	gold quality
sperm	CL:0000019	83.05	gold quality
oocyte	CL:0000023	82.17	gold quality
male germ cell	CL:0000015	82.15	gold quality
metanephros	UBERON:0000081	81.82	gold quality
right uterine tube	UBERON:0001302	81.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.24	gold quality
secondary oocyte	CL:0000655	77.68	silver quality
tibial nerve	UBERON:0001323	76.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.79	gold quality
sural nerve	UBERON:0015488	74.46	gold quality
left lobe of thyroid gland	UBERON:0001120	73.86	gold quality
thyroid gland	UBERON:0002046	73.69	gold quality
metanephros cortex	UBERON:0010533	73.55	gold quality
right lobe of thyroid gland	UBERON:0001119	73.41	gold quality
right testis	UBERON:0004534	73.30	gold quality
calcaneal tendon	UBERON:0003701	73.13	gold quality
small intestine	UBERON:0002108	72.21	gold quality
left testis	UBERON:0004533	71.54	gold quality
olfactory bulb	UBERON:0002264	71.36	gold quality
type B pancreatic cell	CL:0000169	71.17	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	5820.43
E-CURD-119	yes	5451.71
E-HCAD-10	yes	40.25
E-MTAB-7008	yes	32.56
E-ANND-3	yes	7.21
E-CURD-135	no	2266.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, YBX3

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-8064	99.45	66.92	875
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-6755-3P	98.61	66.90	834
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-6742-3P	97.95	64.50	1490

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Comparative analysis of cobalamin binding kinetics (PMID:11788601)
• Megalin and cubilin: multifunctional endocytic receptors. A review. (PMID:11994745)
• proteinuria was due to the lack of cubilin function needed for tubular reabsorption of some, but not all, proteins of the primary urine. (PMID:12687456)
• cubilin and amnionless are subunits of a novel cubilin/amnionless (cubam) complex (PMID:14576052)
• the early cubilin expression and its function in protein and cholesterol uptake suggest an important role for cubilin in the development of the peri-implantation embryo (PMID:15616221)
• Formation of the cubilin recognition site on intrinsic factor (IF) is caused by assembly of two distant domains, which allows the saturated IF protein to be recognized by the receptor. (PMID:15736970)
• interactions of COBALAMIN BINDING proteins with a number of ligands (PMID:17487979)
• This review summarizes recent data on the biological function of cubilin and focuses on its implication in embryonic nutrition and central nervous system malformations. (PMID:17979745)
• light chain endocytosis is predominantly mediated by the megalin-cubilin tandem endocytic receptor and identify endocytosis as a key step in light chain cytotoxicity. (PMID:18448595)
• results show different expression patterns of megalin and cubulin in calculous gallbladders and acalculous gallbladders suggesting an association with gallstone formation and implying a putative role of the two proteins in cholesterol endocytosis (PMID:18791690)
• An association study of 45 folate-related genes in spina bifida: Involvement of cubilin (PMID:19161160)
• Aberrant shedding of megalin and cubilin may contribute to albuminuria in diabetes and to deficiency states of important vitamins and hormones. (PMID:19366958)
• crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB(5-8)) determined at 3.3 A resolution (PMID:20237569)
• cubilin gene polymorphisms have an influence on 25(OH)D3 and 1,25(OH)2D3 plasma levels in type 1 diabetes patients (PMID:20398757)
• There is a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes. (PMID:21355061)
• megalin and cubilin are involved in the metabolism of vitamin D by reabsorbing vitamin D binding protein; dysfunction of these receptors is likely to be associated with the development of vitamin D deficiency in patients with chronic kidney disease (PMID:21595846)
• amnionless is essential for the correct luminal expression of cubilin in humans. (PMID:21750092)
• These data suggest that CUBN is not involved in cleft lip or palate onset in the investigated Italian population (PMID:21781439)
• A novel 1-bp homozygous deletion of the cubilin was found to be the cause of proteinuria with nephrotic syndrome. (PMID:21903995)
• used immunocytochemistry and reverse transcription-polymerase chain reaction on laser-captured glomeruli to demonstrate synthesis and expression of cubilin in glomerular podocytes (PMID:22337902)
• Expression of megalin and cubilin is decreased during experimental endotoxemia, which may contribute to an increase in urine levels of albumin during acute renal failure. (PMID:22437417)
• CUBN rs7918972 as a novel risk variant for renal function loss (PMID:22574174)
• Single nucleotide polymorphisms in cubilin gene is associated with iron overload. (PMID:22761678)
• Our genetic screening of 154 families of patients with inherited cobalamin malabsorption revealed population-specific mutations, mutational hotspots, and functionally distinct regions in the three causal genes: CUBN, AMN, and GIF. (PMID:22929189)
• The p.I1e2984Val variant of cubulin is part of a larger haplotype in European populations that is almost absent in West Africans. (PMID:23114252)
• Data suggest that endodermal layer of yolk sac and syncytiotrophoblast/cytotrophoblast cells of placental villi express cubilin mRNA/protein; expression of cubilin mRNA/protein is up-regulated as gestation/placentation progresses. (PMID:23978537)
• MA is associated with CVD irrespective of the presence of the CUBN risk allele. These results challenge the concept that albuminuria in the setting of this mutation is benign. (PMID:24052458)
• LOS treatment decreased microalbuminuria induced by Cd apparently through a cubilin receptor-dependent mechanism but independent of megalin. (PMID:24093454)
• Cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apolipoprotein (apo)A-I, significantly increasing urinary loss of albumin and apoA-I. (PMID:24357674)
• The variant rs11254363 of the CUBN gene was associated with a decreased risk of developing congenital heart disease in Han Chinese populations (PMID:24533076)
• predisposition to multibacillary leprosy in Vietnam is associated with CUBN and NEBL common variants in the chromosome 10p13 linkage region (PMID:24563210)
• CUBN was associated with albuminuria in type 2 diabetes patients. (PMID:26631737)
• The CUBN haplotypes were associated with an altered gastric cancer risk. (PMID:26959381)
• CUBN SNP rs1801239 (I2984V), previously associated with albuminuria, was significantly associated with T2D-ESRD in blacks. (PMID:27197912)
• Study identified CUBN as a marker for risk stratification of patients with renal cell carcinoma (RCC). Lack of CUBN expression was significantly associated with early disease progression and poor patient outcome, independent of T-stage, Fuhrman grade and nodal status. Owing to a highly RCC-specific expression profile, CUBN expression also has a potential role in clinical cancer differential diagnostics. (PMID:28052770)
• Tumoral expression of cubilin is a positive predictive marker for treatment of metastatic renal cell cancer patients with sunitinib and sorafenib. (PMID:28260162)
• in teens with positive recto-vaginal group B streptococcus colonization, placental mRNA expression of cubilin is lower compared to those who tested negative for this infection (PMID:28622535)
• Cubilin is involved in 25(OH) vitamin D uptake by adipocytes. (PMID:29186386)
• Study shows that cubilin mutations (novel and some previously reported) and all previously reported amnionless missense mutations resulted in endoplasmic reticulum retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin. (PMID:29402915)
• Data indicate the crystal structure of amnionless (AMN) in complex with the amino-terminal region of intrinsic factor-cobalamin receptor (cubilin). (PMID:30523278)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cubn	ENSDARG00000087013
mus_musculus	Cubn	ENSMUSG00000026726
rattus_norvegicus	Cubn	ENSRNOG00000029047
drosophila_melanogaster	tok	FBGN0004885
drosophila_melanogaster	Cubn2	FBGN0259140

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), 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)

Protein

Protein identifiers

Cubilin — O60494 (reviewed: O60494)

Alternative names: 460 kDa receptor, Intestinal intrinsic factor receptor, Intrinsic factor-cobalamin receptor, Intrinsic factor-vitamin B12 receptor

All UniProt accessions (2): O60494, H7C480

UniProt curated annotations — full annotation on UniProt →

Function. Endocytic receptor which plays a role in lipoprotein, vitamin and iron metabolism by facilitating their uptake. Acts together with LRP2 to mediate endocytosis of high-density lipoproteins, GC, hemoglobin, ALB, TF and SCGB1A1. Acts together with AMN to mediate endocytosis of the CBLIF-cobalamin complex. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the CBLIF-cobalamin complex. Ligand binding requires calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface.

Subunit / interactions. Interacts with AMN. Component of the cubam complex composed of one CUBN trimer and one AMN chain. The cubam complex can dimerize. Interacts with LRP2 in a dual-receptor complex in a calcium-dependent manner. Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with LRP1 and PID1/PCLI1.

Subcellular location. Apical cell membrane. Cell membrane. Membrane. Coated pit. Endosome. Lysosome membrane.

Tissue specificity. Detected in kidney cortex (at protein level). Expressed in kidney proximal tubule cells, placenta, visceral yolk-sac cells and in absorptive intestinal cells. Expressed in the epithelium of intestine and kidney.

Post-translational modifications. The precursor is cleaved by a trans-Golgi proteinase furin, removing a propeptide. N-glycosylated.

Disease relevance. Imerslund-Grasbeck syndrome 1 (IGS1) [MIM:261100] A form of Imerslund-Grasbeck syndrome, a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in infancy or early childhood. Clinical manifestations include failure to thrive, infections and neurological damage. Mild proteinuria, with no signs of kidney disease, is present in about half of the patients. The disease is caused by variants affecting the gene represented in this entry. Proteinuria, chronic benign (PROCHOB) [MIM:618884] An autosomal recessive condition characterized by isolated, non-progressive proteinuria in absence of renal disease and hypertension. Onset of proteinuria is in the first decade of life. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The CUB domains 5 to 8 mediate binding to CBLIF and ALB. CUB domains 1 and 2 mediate interaction with LRP2. The cubam complex is composed of a 400 Angstrom long stem and a globular crown region. The stem region is probably formed by AMN and the CUBN N-terminal region, including the EGF-like domains. The crown is probably formed by the CUBN CUB domains.

RefSeq proteins (1): NP_001072* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR000859	CUB_dom	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR024731	NELL2-like_EGF	Domain
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain

Pfam: PF00008, PF00431, PF07645, PF12947

UniProt features (281 total): disulfide bond 66, sequence variant 64, glycosylation site 47, strand 36, domain 34, binding site 19, turn 4, helix 3, sequence conflict 2, signal peptide 1, propeptide 1, chain 1, region of interest 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6GJE	X-RAY DIFFRACTION	2.3
3KQ4	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

No AlphaFold model available for O60494 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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): 35–36 (cleavage; by furin)

Ligand- & substrate-binding residues (19): 980; 988; 1027; 1029; 1030; 1096; 1105; 1146; 1148; 1149; 1213; 1221 …

Post-translational modifications (1): 3008

Disulfide bonds (66): 136–147, 141–156, 158–167, 174–190, 184–199, 201–210, 267–280, 274–289, 292–303, 353–366, 360–376, 399–409, 404–418, 420–429, 436–447, 441–456, 458–467, 474–500, 527–549, 590–616 …

Glycosylation sites (47): 3295, 3357, 3430, 3457, 3533, 3576, 105, 428, 482, 711, 749, 781, 857, 957, 984, 1092, 1168, 1217, 1285, 1307 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-196791	Vitamin D (calciferol) metabolism
R-HSA-3359462	Defective AMN causes MGA1
R-HSA-3359463	Defective CUBN causes MGA1
R-HSA-8964011	HDL clearance
R-HSA-9758881	Uptake of dietary cobalamins into enterocytes

MSigDB gene sets: 243 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, SHEPARD_BMYB_MORPHOLINO_UP, GOCC_VACUOLAR_MEMBRANE, GOCC_CELL_SURFACE, GOBP_VESICLE_MEDIATED_TRANSPORT, BROWNE_HCMV_INFECTION_48HR_DN, TCF4_Q5, chr10p13, GOBP_COBALAMIN_METABOLIC_PROCESS, GOBP_TETRAPYRROLE_METABOLIC_PROCESS, GOBP_VITAMIN_TRANSPORT, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPOPROTEIN_LOCALIZATION, GOCC_APICAL_PLASMA_MEMBRANE

GO Biological Process (12): tissue homeostasis (GO:0001894), receptor-mediated endocytosis (GO:0006898), cholesterol metabolic process (GO:0008203), cobalamin metabolic process (GO:0009235), response to bacterium (GO:0009617), cobalamin transport (GO:0015889), lipoprotein transport (GO:0042953), establishment of localization in cell (GO:0051649), lipid metabolic process (GO:0006629), endocytosis (GO:0006897), steroid metabolic process (GO:0008202), protein transport (GO:0015031)

GO Molecular Function (7): calcium ion binding (GO:0005509), cobalamin binding (GO:0031419), signaling receptor activity (GO:0038023), cargo receptor activity (GO:0038024), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (21): lysosomal membrane (GO:0005765), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), membrane (GO:0016020), apical plasma membrane (GO:0016324), endocytic vesicle (GO:0030139), extrinsic component of external side of plasma membrane (GO:0031232), brush border membrane (GO:0031526), microvillus membrane (GO:0031528), lysosomal lumen (GO:0043202), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), lysosome (GO:0005764), brush border (GO:0005903), cell projection membrane (GO:0031253), apical part of cell (GO:0045177)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Defects in cobalamin (B12) metabolism	2
Metabolism of steroids	1
Plasma lipoprotein clearance	1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	4
cytoplasm	3
cellular anatomical structure	3
vesicle-mediated transport	2
lysosome	2
cytoplasmic vesicle	2
intracellular membrane-bounded organelle	2
membrane	2
apical part of cell	2
plasma membrane region	2
cell projection membrane	2
microvillus	2
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
endocytosis	1
sterol metabolic process	1
secondary alcohol metabolic process	1
tetrapyrrole metabolic process	1
response to other organism	1
vitamin transport	1
nitrogen compound transport	1
protein transport	1
lipoprotein localization	1
establishment of localization	1
cellular localization	1
primary metabolic process	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
lipid metabolic process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
metal ion binding	1
vitamin binding	1
tetrapyrrole binding	1
heterocyclic compound binding	1
molecular transducer activity	1
molecular_function	1
molecular adaptor activity	1

Protein interactions and networks

STRING

1174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CUBN	AMN	Q9BXJ7	999
CUBN	LRP2	P98164	999
CUBN	ALB	P02768	992
CUBN	CBLIF	P27352	984
CUBN	APOA1	P02647	972
CUBN	GC	P02774	970
CUBN	CLCN5	P51795	868
CUBN	SLC9A3	P48764	835
CUBN	DAB2	P98082	811
CUBN	CBL	P22681	806
CUBN	HP	P00737	747
CUBN	TCN2	P20062	706
CUBN	AMBP	P00977	704
CUBN	TCN1	P20061	671
CUBN	PLB1	Q6P1J6	669

IntAct

9 interactions, top by confidence:

A	B	Type	Score
AMN	CUBN	psi-mi:“MI:0407”(direct interaction)	0.600
AMN	CUBN	psi-mi:“MI:0915”(physical association)	0.600
CBLIF	CUBN	psi-mi:“MI:0407”(direct interaction)	0.560
CUBN	CUBN	psi-mi:“MI:0915”(physical association)	0.400
LMP2	WWP2	psi-mi:“MI:0914”(association)	0.350
RRP1B	YY2	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): CUBN (Affinity Capture-Western), GIF (Reconstituted Complex), CUBN (Reconstituted Complex), CUBN (Affinity Capture-MS), CUBN (Affinity Capture-MS), CUBN (Reconstituted Complex), CUBN (Protein-peptide), LRP1 (Affinity Capture-Western), PID1 (Affinity Capture-Western), CUBN (Two-hybrid)

ESM2 similar proteins: A0A1D5NSM8, A0A1L8HYT7, A2AJX4, B1AUH1, B3DK56, B3EX02, E2RK30, E9PZ36, F1RWC3, F8W3R9, O54767, O60494, O70244, P08922, P08F94, P20239, P47984, P56677, P79953, P86091, P97435, P98072, P98073, P98074, Q0IIH7, Q0V8T3, Q0V8T5, Q2QI47, Q3UZ09, Q5VYJ5, Q63132, Q66TN7, Q6DIV5, Q6YI48, Q769J6, Q78DX7, Q7M761, Q7RTY7, Q7RTY8, Q7RTZ1

Diamond homologs: A0A0C5PRQ1, A0FKN6, A0JNA2, A8Q2D1, C6K2K4, C9D7R3, D2KBH9, D5FM34, D5FM37, D5FM38, K7Z9Q9, O16977, O17264, O35276, O35375, O43897, O57382, O57460, O60462, O60494, O70244, P07584, P0DM61, P0DM62, P13497, P28825, P28826, P31579, P31580, P31581, P42674, P55112, P55113, P55114, P55115, P84748, P91828, P98060, P98061, P98068

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2582 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	63
Likely pathogenic	110
Uncertain significance	1249
Likely benign	653
Benign	246

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072126	NM_001081.4(CUBN):c.7013del (p.Gly2338fs)	Pathogenic
1074985	NM_001081.4(CUBN):c.7051G>T (p.Gly2351Ter)	Pathogenic
1075676	NM_001081.4(CUBN):c.2191_2192del (p.Thr731fs)	Pathogenic
1076401	NM_001081.4(CUBN):c.1892del (p.Thr631fs)	Pathogenic
1179177	NM_001081.4(CUBN):c.796G>T (p.Glu266Ter)	Pathogenic
1322176	NM_001081.4(CUBN):c.10233G>A (p.Trp3411Ter)	Pathogenic
1427549	NM_001081.4(CUBN):c.8684_8687del (p.Ser2895fs)	Pathogenic
1444492	NM_001081.4(CUBN):c.424C>T (p.Gln142Ter)	Pathogenic
1444519	NM_001081.4(CUBN):c.7802G>A (p.Trp2601Ter)	Pathogenic
1705570	NM_001081.4(CUBN):c.4689T>A (p.Cys1563Ter)	Pathogenic
1992848	NM_001081.4(CUBN):c.9783del (p.Thr3261_Leu3262insTer)	Pathogenic
2009822	NM_001081.4(CUBN):c.8049del (p.Lys2683fs)	Pathogenic
2032699	NM_001081.4(CUBN):c.5701G>T (p.Glu1901Ter)	Pathogenic
2104999	NM_001081.4(CUBN):c.794dup (p.Asp265fs)	Pathogenic
2193032	NM_001081.4(CUBN):c.10557_10558del (p.Gly3520fs)	Pathogenic
2423663	NC_000010.10:g.(?16961942)(16970322_?)del	Pathogenic
2628983	NM_001081.4(CUBN):c.8355del (p.Asp2786fs)	Pathogenic
2718935	NM_001081.4(CUBN):c.10520C>A (p.Ser3507Ter)	Pathogenic
2721529	NM_001081.4(CUBN):c.5856del (p.Lys1954fs)	Pathogenic
2731233	NM_001081.4(CUBN):c.3138del (p.Ala1047fs)	Pathogenic
2736019	NM_001081.4(CUBN):c.6118C>T (p.Arg2040Ter)	Pathogenic
2793997	NM_001081.4(CUBN):c.7145_7146del (p.Asp2381_Phe2382insTer)	Pathogenic
2859831	NM_001081.4(CUBN):c.3578G>A (p.Trp1193Ter)	Pathogenic
2958744	NM_001081.4(CUBN):c.8165del (p.Pro2722fs)	Pathogenic
30291	NM_001081.4(CUBN):c.3329+1G>T	Pathogenic
3220910	NM_001081.4(CUBN):c.591C>G (p.Tyr197Ter)	Pathogenic
3235994	NM_001081.4(CUBN):c.4042G>T (p.Gly1348Ter)	Pathogenic
3235995	NM_001081.4(CUBN):c.6297_6298insT (p.Arg2100Ter)	Pathogenic
3244830	NC_000010.10:g.(?17151619)(17157616_?)del	Pathogenic
3255214	NM_001081.4(CUBN):c.10009_10012del (p.Leu3337fs)	Pathogenic

SpliceAI

10556 predictions. Top by Δscore:

Variant	Effect	Δscore
10:16828799:A:AC	donor_gain	1.0000
10:16828800:C:CC	donor_gain	1.0000
10:16828803:A:AC	donor_gain	1.0000
10:16828803:ACGC:A	donor_gain	1.0000
10:16828804:C:CA	donor_gain	1.0000
10:16828804:CG:C	donor_gain	1.0000
10:16828804:CGCC:C	donor_gain	1.0000
10:16828804:CGCCT:C	donor_gain	1.0000
10:16829036:ACATC:A	acceptor_gain	1.0000
10:16829037:CATC:C	acceptor_gain	1.0000
10:16829037:CATCC:C	acceptor_gain	1.0000
10:16829038:ATC:A	acceptor_gain	1.0000
10:16829038:ATCCT:A	acceptor_loss	1.0000
10:16829039:TC:T	acceptor_gain	1.0000
10:16829040:CC:C	acceptor_gain	1.0000
10:16829040:CCT:C	acceptor_loss	1.0000
10:16829041:C:CC	acceptor_gain	1.0000
10:16829042:T:A	acceptor_loss	1.0000
10:16835197:T:C	acceptor_gain	1.0000
10:16840883:A:AC	donor_gain	1.0000
10:16840883:ACTGT:A	donor_gain	1.0000
10:16840884:C:CT	donor_gain	1.0000
10:16840884:CTGTC:C	donor_gain	1.0000
10:16841048:C:CC	acceptor_gain	1.0000
10:16869630:TCTTA:T	donor_loss	1.0000
10:16869631:CTTA:C	donor_loss	1.0000
10:16869632:TTA:T	donor_loss	1.0000
10:16869633:TACCC:T	donor_loss	1.0000
10:16869634:A:AC	donor_gain	1.0000
10:16869635:C:CC	donor_gain	1.0000

AlphaMissense

23998 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:16913904:C:A	W2480C	0.995
10:16913904:C:G	W2480C	0.995
10:16982565:C:A	W1538C	0.995
10:16982565:C:G	W1538C	0.995
10:17104436:C:G	C467S	0.995
10:17104437:A:T	C467S	0.995
10:17114157:C:A	W251C	0.995
10:17114157:C:G	W251C	0.995
10:16828952:C:A	W3539C	0.994
10:16828952:C:G	W3539C	0.994
10:16828997:G:C	S3524R	0.994
10:16828997:G:T	S3524R	0.994
10:16828999:T:G	S3524R	0.994
10:16954409:A:C	F1612C	0.994
10:16954409:A:G	F1612S	0.994
10:16990434:C:G	C1417S	0.994
10:16990435:A:G	C1417R	0.994
10:16990435:A:T	C1417S	0.994
10:17100021:C:A	W583C	0.993
10:17100021:C:G	W583C	0.993
10:17109711:C:G	C347S	0.993
10:17109712:A:T	C347S	0.993
10:16928172:C:G	A2086P	0.992
10:16937640:A:G	W1960R	0.992
10:16937640:A:T	W1960R	0.992
10:16939058:A:G	W1880R	0.992
10:16939058:A:T	W1880R	0.992
10:16947324:G:C	S1751R	0.992
10:16947324:G:T	S1751R	0.992
10:16947326:T:G	S1751R	0.992

dbSNP variants (sampled 300 via entrez): RS1000013462 (10:16859348 T>C), RS1000014802 (10:17035894 T>C), RS1000019204 (10:16930248 A>G), RS1000042237 (10:17059628 A>G), RS1000047222 (10:16881802 T>A), RS1000058298 (10:17009560 C>G), RS1000058949 (10:17113782 C>A), RS1000065646 (10:17047080 T>A), RS1000067320 (10:16895769 G>A), RS1000071251 (10:16958553 G>A), RS1000077750 (10:17000265 C>A,G), RS1000080493 (10:16901983 A>G), RS1000117887 (10:16988775 A>G), RS1000128299 (10:17000424 C>G,T), RS1000139621 (10:16857185 G>A)

Disease associations

OMIM: gene MIM:602997 | disease phenotypes: MIM:261100, MIM:618884

GenCC curated gene-disease

Disease	Classification	Inheritance
Imerslund-Grasbeck syndrome type 1	Definitive	Autosomal recessive
proteinuria, chronic benign	Strong	Autosomal recessive
Imerslund-Grasbeck syndrome	Supportive	Autosomal recessive

Mondo (7): Imerslund-Grasbeck syndrome (MONDO:0009853), proteinuria, chronic benign (MONDO:0030042), Imerslund-Grasbeck syndrome type 1 (MONDO:0100156), proteinuria (MONDO:0003634), chronic kidney disease (MONDO:0005300), focal segmental glomerulosclerosis (MONDO:0100313), autism spectrum disorder (MONDO:0005258)

Orphanet (2): Imerslund-Gräsbeck syndrome (Orphanet:35858), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000206	Glossitis
HP:0000707	Abnormality of the nervous system
HP:0000726	Dementia
HP:0000750	Delayed speech and language development
HP:0000980	Pallor
HP:0001252	Hypotonia
HP:0001289	Confusion
HP:0001508	Failure to thrive
HP:0001649	Tachycardia
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001889	Megaloblastic anemia
HP:0001892	Abnormal bleeding
HP:0001923	Reticulocytosis
HP:0001972	Macrocytic anemia
HP:0002013	Vomiting
HP:0002019	Constipation
HP:0002376	Developmental regression
HP:0002721	Immunodeficiency
HP:0002907	Microscopic hematuria
HP:0003401	Paresthesia
HP:0003474	Somatic sensory dysfunction
HP:0004396	Poor appetite
HP:0004821	Hypersegmentation of neutrophil nuclei
HP:0004823	Anisopoikilocytosis

GWAS associations

50 associations (top):

Study	Trait	p-value
GCST000337_26	Quantitative traits	6.000000e-06
GCST000358_2	Folate pathway vitamin levels	1.000000e-06
GCST000483_3	Folate pathway vitamin levels	3.000000e-09
GCST000891_4	Whole-brain volume	3.000000e-06
GCST000988_1	Urinary albumin excretion	1.000000e-11
GCST002087_11	Homocysteine levels	8.000000e-10
GCST002087_15	Homocysteine levels	8.000000e-10
GCST002221_72	Cholesterol, total	3.000000e-11
GCST002559_4	Vitamin B levels in ischemic stroke	2.000000e-13
GCST002919_3	Colorectal cancer	7.000000e-08
GCST002937_2	Molybdenum levels	3.000000e-07
GCST003253_1	Microalbuminuria	1.000000e-10
GCST003254_2	Urinary albumin-to-creatinine ratio in non-diabetics	4.000000e-06
GCST003255_8	Urinary albumin-to-creatinine ratio	2.000000e-10
GCST003774_1	Urinary albumin-to-creatinine ratio	2.000000e-08
GCST004235_38	Total cholesterol levels	5.000000e-11
GCST004616_78	Platelet distribution width	6.000000e-17
GCST005387_2	Binge eating behaviour in bipolar disorder	1.000000e-07
GCST006463_14	Urinary albumin excretion (no hypertensive medication)	1.000000e-51
GCST006463_15	Urinary albumin excretion (no hypertensive medication)	4.000000e-09
GCST006463_16	Urinary albumin excretion (no hypertensive medication)	3.000000e-84
GCST006586_24	Urinary albumin excretion	2.000000e-92
GCST006586_25	Urinary albumin excretion	3.000000e-11
GCST006586_26	Urinary albumin excretion	9.000000e-09
GCST006586_27	Urinary albumin excretion	2.000000e-107
GCST007202_3	High density lipoprotein cholesterol levels	1.000000e-06
GCST007718_1	Urinary albumin-to-creatinine ratio	1.000000e-51
GCST007718_2	Urinary albumin-to-creatinine ratio	1.000000e-40
GCST007718_3	Urinary albumin-to-creatinine ratio	4.000000e-62
GCST008610_2	Proteinuria	3.000000e-15

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004620	vitamin B12 measurement
EFO:0005089	whole-brain volume
EFO:0004285	albuminuria
EFO:0004578	homocysteine measurement
EFO:0004574	total cholesterol measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0007984	platelet component distribution width
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004531	urate measurement
EFO:0005420	grey matter volume measurement
EFO:0010408	triacylglycerol 50:1 measurement
EFO:0009963	bipolar I disorder
EFO:0007985	platelet crit

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D007676	Kidney Failure, Chronic	C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
C538556	Imerslund-Grasbeck syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Valproic Acid	decreases expression, increases methylation	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases methylation, decreases methylation, affects cotreatment	1
sodium arsenite	increases expression	1
ochratoxin A	decreases acetylation	1
entinostat	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Methamphetamine	affects response to substance	1
N-Nitrosopyrrolidine	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vitamin K 3	decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 finite cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3YU	WG2625	Finite cell line	Male
CVCL_B3Z4	WG3086	Finite cell line	Male
CVCL_B4EF	WG3705	Finite cell line
CVCL_C0LP	GM28311	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00234871	PHASE4	COMPLETED	Tarka® vs. Lotrel® in Hypertensive, Diabetic Subjects With Renal Disease (TANDEM)
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus
NCT00369538	PHASE4	SUSPENDED	Specific Blockage of Angiotensine 2 and Podocyturia in Glomerular Nephropathies With Hypertension and Proteinuria
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00550095	PHASE4	COMPLETED	To Assess the Effects of Valsartan on Albuminuria/Proteinuria in Hypertensive Patients With Type 2 Diabetes Mellitus
NCT00674596	PHASE4	COMPLETED	The Effect of Renin Angiotensin System Blockage (RAS) Blockade On PTX3 Levels In Diabetic Patients With Proteinuria
NCT00858299	PHASE4	UNKNOWN	The Change of Urinary Angiotensinogen Excretion After Valsartan Treatment in Patients With Persistent Proteinuria
NCT00893425	PHASE4	COMPLETED	Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria
NCT00921570	PHASE4	COMPLETED	The Effects of Renin Angiotensin System Blockage (RAS), Calcium Channel Blocker and Combined Drugs on TWEAK, PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension
NCT00961207	PHASE4	TERMINATED	Triple Blockade of the Renin Angiotensin Aldosterone System in Diabetic (Type 1&2) Proteinuric Patients
NCT01169857	PHASE4	WITHDRAWN	Velcade for Proliferative Lupus Nephritis
NCT01219413	PHASE4	COMPLETED	Influence of Aliskiren on Proteinuria
NCT01386554	PHASE4	COMPLETED	Acthar for Treatment of Proteinuria in Membranous Nephropathy Patients
NCT01512862	PHASE4	UNKNOWN	Anti-proteinuric Effect of Calcitriol in Non-diabetic Kidney Disease Patients
NCT01541267	PHASE4	COMPLETED	The Effect of Various Types of the Renin-angiotensin-aldosterone System Blockade on Proteinuria
NCT01637259	PHASE4	COMPLETED	MARCH Renal Substudy
NCT01703234	PHASE4	COMPLETED	FGF-23 and Endothelial Dysfunction in Diabetic Proteinuric Patients
NCT01820832	PHASE4	UNKNOWN	Oral Calcitriol for Reduction of Mild Proteinuria in Patients With CKD
NCT01827202	PHASE4	COMPLETED	RAS Quantification in Patients With Aliskiren or Candesartan
NCT02057523	PHASE4	TERMINATED	Acthar as Rescue Therapy for Transplant Glomerulopathy in Kidney Transplant Recipients
NCT02063100	PHASE4	UNKNOWN	Efficacy and Safety of Shenyankangfu Tablets for Primary Glomerulonephritis
NCT02382523	PHASE4	WITHDRAWN	Acthar on Proteinuria in IgA Nephropathy Patients
NCT02522650	PHASE4	UNKNOWN	A Crossover Pilot Study of the Effect of Amiloride on Proteinuria
NCT03195023	PHASE4	UNKNOWN	Effect of RAS Blockers on CKD Progression in Elderly Patients With Non Proteinuric Nephropathies (PROERCAN01)
NCT03550859	PHASE4	UNKNOWN	HMG-CoA Reductase add-on in Chronic Kidney Disease Patients With Proteinuria
NCT03983551	PHASE4	COMPLETED	Comparing the Renal Effect of Dipeptidyl-peptidase 4 Inhibitors and Sulfonylureas
NCT04531397	PHASE4	WITHDRAWN	Efficacy and Safety of Dapagliflozin in Children With Proteinuric Chronic Kidney Disease
NCT04534270	PHASE4	COMPLETED	Efficacy and Safety of Dapagliflozin in Children With Proteinuria
NCT06374043	PHASE4	COMPLETED	Decentralized N=1 Study: A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin.
NCT07030894	PHASE4	RECRUITING	Nefecon and Ambrisentan in IgA Nephropathy
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT07358520	PHASE4	NOT_YET_RECRUITING	Clinical Study on the Use of Huaier Granules for the Treatment of Proteinuria Related to Bevacizumab and Anlotinib in Lung Cancer Patients
NCT00073710	PHASE4	COMPLETED	Study to Evaluate the Effects of Zemplar Injection and Calcijex on Intestinal Absorption of Calcium
NCT00125593	PHASE4	COMPLETED	Study of Heart and Renal Protection
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00155246	PHASE4	COMPLETED	Efficacy of Pentoxifylline on Chronic Kidney Disease
NCT00175149	PHASE4	TERMINATED	Active Vitamin D Effect on Left Ventricular Hypertrophy
NCT00184769	PHASE4	COMPLETED	Growth Hormone Treatment in Infants Aged 1 to 2 Years With Chronic Renal Insufficiency (CRI) and Growth Retardation.
NCT00190580	PHASE4	COMPLETED	Kanagawa Valsartan Trial (KVT): Effects of Valsartan on Renal and Cardiovascular Disease