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CUBN cubilin [ Homo sapiens (human) ]

Gene ID: 8029, updated on 23-Mar-2024

Summary

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Official Symbol
CUBNprovided by HGNC
Official Full Name
cubilinprovided by HGNC
Primary source
HGNC:HGNC:2548
See related
Ensembl:ENSG00000107611 MIM:602997; AllianceGenome:HGNC:2548
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IGS; IFCR; IGS1; MGA1; gp280
Summary
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. [provided by RefSeq, Jul 2008]
Expression
Biased expression in kidney (RPKM 65.4) and small intestine (RPKM 9.4) See more
Orthologs
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Genomic context

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Location:
10p13
Exon count:
71
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (16823966..17129811, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (16842423..17148343, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (16865965..17171810, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene Ras suppressor protein 1 Neighboring gene uncharacterized LOC124902384 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:16801281-16801433 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2179 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:16829435-16829935 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3102 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3103 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3104 Neighboring gene uncharacterized LOC105376435 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3105 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3106 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3107 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:16864864-16865015 Neighboring gene MPRA-validated peak881 silencer Neighboring gene MPRA-validated peak882 silencer Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:16933270-16934469 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr10:16942960-16943677 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr10:16970960-16971553 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr10:17010389-17010952 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:17026880-17027039 Neighboring gene GATA motif-containing MPRA enhancer 283 Neighboring gene Sharpr-MPRA regulatory region 1431 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:17104252-17105451 Neighboring gene MPRA-validated peak883 silencer Neighboring gene MPRA-validated peak884 silencer Neighboring gene MED14-independent group 3 enhancer GRCh37_chr10:17157167-17158366 Neighboring gene tRNA aspartic acid methyltransferase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2181 Neighboring gene ReSE screen-validated silencer GRCh37_chr10:17268719-17268933 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3108 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2182 Neighboring gene VIM antisense RNA 1 Neighboring gene vimentin

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Four missense genetic variants in CUBN are associated with higher levels of eGFR in non-diabetes but not in diabetes mellitus or its subtypes: A genetic association study in Europeans. Uglebjerg N, et al. Front Endocrinol (Lausanne), 2023. PMID 36926036, Free PMC Article
  2. Novel pathogenic variants in CUBN uncouple proteinuria from renal function. Gan C, et al. J Transl Med, 2022 Oct 20. PMID 36266725, Free PMC Article
  3. Clinical and genetic characterization of children with cubilin variants. Cicek N, et al. Pediatr Nephrol, 2023 Apr. PMID 36112210
  4. Cubilin, the intrinsic factor-vitamin B12 receptor. Kozyraki R, et al. Vitam Horm, 2022. PMID 35337634
  5. CUBN gene mutations may cause focal segmental glomerulosclerosis (FSGS) in children. Yang J, et al. BMC Nephrol, 2022 Jan 3. PMID 34979989, Free PMC Article

See all (100) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Identification of novel pathogenic variants of CUBN in patients with isolated proteinuria.
    Title: Identification of novel pathogenic variants of CUBN in patients with isolated proteinuria.
  2. Human parietal epithelial cells (PECs) and proteinuria in lupus nephritis: a role for ClC-5, megalin, and cubilin?
    Title: Human parietal epithelial cells (PECs) and proteinuria in lupus nephritis: a role for ClC-5, megalin, and cubilin?
  3. Four missense genetic variants in CUBN are associated with higher levels of eGFR in non-diabetes but not in diabetes mellitus or its subtypes: A genetic association study in Europeans.
    Title: Four missense genetic variants in CUBN are associated with higher levels of eGFR in non-diabetes but not in diabetes mellitus or its subtypes: A genetic association study in Europeans.
  4. Clinical and genetic characterization of children with cubilin variants.
    Title: Clinical and genetic characterization of children with cubilin variants.
  5. Novel pathogenic variants in CUBN uncouple proteinuria from renal function.
    Title: Novel pathogenic variants in CUBN uncouple proteinuria from renal function.
  6. Clinical and genetic characterization of a cohort of proteinuric patients with biallelic CUBN variants.
    Title: Clinical and genetic characterization of a cohort of proteinuric patients with biallelic CUBN variants.
  7. CUBN gene mutations may cause focal segmental glomerulosclerosis (FSGS) in children.
    Title: CUBN gene mutations may cause focal segmental glomerulosclerosis (FSGS) in children.
  8. Cubilin, the intrinsic factor-vitamin B12 receptor.
    Title: Cubilin, the intrinsic factor-vitamin B12 receptor.
  9. Genetic Variability in the Iron Homeostasis Pathway and Patient Outcomes After Aneurysmal Subarachnoid Hemorrhage.
    Title: Genetic Variability in the Iron Homeostasis Pathway and Patient Outcomes After Aneurysmal Subarachnoid Hemorrhage.
  10. Tuberculosis risk is associated with genetic polymorphisms in the LRP2, CUBN, and VDR genes.
    Title: Tuberculosis risk is associated with genetic polymorphisms in the LRP2, CUBN, and VDR genes.
Submit: New GeneRIF Correction See all GeneRIFs (62)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Imerslund-Grasbeck syndrome type 1
MedGen: C4016819 OMIM: 261100 GeneReviews: Not available
Compare labs
Proteinuria, chronic benign
MedGen: C5394384 OMIM: 618884 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease.
EBI GWAS Catalog
CUBN is a gene locus for albuminuria.
EBI GWAS Catalog
Discovery and refinement of loci associated with lipid levels.
EBI GWAS Catalog
Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial.
EBI GWAS Catalog
Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.
EBI GWAS Catalog
Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations.
EBI GWAS Catalog
Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease.
EBI GWAS Catalog
Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ90055, FLJ90747

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables cargo receptor activity EXP
Inferred from Experiment
more info
 PubMed 
enables cargo receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables cargo receptor activity TAS
Traceable Author Statement
more info
 PubMed 
enables cobalamin binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables signaling receptor activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in cholesterol metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cobalamin metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cobalamin transport IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cobalamin transport TAS
Traceable Author Statement
more info
  
involved_in establishment of localization in cell IEA
Inferred from Electronic Annotation
more info
  
involved_in lipoprotein transport IEA
Inferred from Electronic Annotation
more info
  
involved_in receptor-mediated endocytosis NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in response to bacterium IEA
Inferred from Electronic Annotation
more info
  
involved_in tissue homeostasis NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IEA
Inferred from Electronic Annotation
more info
  
located_in apical plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in apical plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in apical plasma membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in brush border membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in brush border membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in clathrin-coated pit IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endocytic vesicle IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
  
located_in endosome IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular exosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extrinsic component of external side of plasma membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in lysosomal lumen TAS
Traceable Author Statement
more info
  
located_in lysosomal membrane IEA
Inferred from Electronic Annotation
more info
  
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in microvillus membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
part_of receptor complex IPI
Inferred from Physical Interaction
more info
 PubMed 
part_of receptor complex ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
cubilin
Names
460 kDa receptor
cubilin (intrinsic factor-cobalamin receptor)
intestinal intrinsic factor receptor
intrinsic factor-vitamin B12 receptor

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008967.1 RefSeqGene

    Range
    5001..310852
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_540

mRNA and Protein(s)

  1. NM_001081.4 → NP_001072.2  cubilin precursor

    See identical proteins and their annotated locations for NP_001072.2

    Status: REVIEWED

    Source sequence(s)
    AC067747, AF034611, AL365215, AL731551, BP270790, BP271329
    Consensus CDS
    CCDS7113.1
    UniProtKB/Swiss-Prot
    B0YIZ4, O60494, Q5VTA6, Q96RU9
    UniProtKB/TrEMBL
    Q7LC53
    Related
    ENSP00000367064.4, ENST00000377833.10
    Conserved Domains (7) summary
    smart00179
    Location:305 → 348
    EGF_CA; Calcium-binding EGF-like domain
    cd00041
    Location:1620 → 1733
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    cd00054
    Location:170 → 210
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    pfam00431
    Location:1978 → 2088
    CUB; CUB domain
    pfam12947
    Location:353 → 387
    EGF_3; EGF domain
    cd22201
    Location:32 → 135
    cubilin_NTD; N-terminal domain of cubilin and similar proteins
    cl00049
    Location:1048 → 1157
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    16823966..17129811 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011519710.3 → XP_011518012.1  cubilin isoform X2

    Conserved Domains (2) summary
    cd00041
    Location:274 → 387
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    pfam00431
    Location:632 → 742
    CUB; CUB domain

  2. XM_011519709.3 → XP_011518011.1  cubilin isoform X1

    Conserved Domains (3) summary
    cd00041
    Location:282 → 395
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    pfam00431
    Location:640 → 750
    CUB; CUB domain
    cl00049
    Location:2 → 45
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

  3. XM_011519711.4 → XP_011518013.1  cubilin isoform X3

    Conserved Domains (2) summary
    cd00041
    Location:234 → 347
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    pfam00431
    Location:592 → 702
    CUB; CUB domain

  4. XM_011519708.3 → XP_011518010.1  cubilin isoform X4

    Conserved Domains (6) summary
    smart00179
    Location:263 → 304
    EGF_CA; Calcium-binding EGF-like domain
    cd00041
    Location:1620 → 1733
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.
    cd00054
    Location:170 → 210
    EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...
    pfam00431
    Location:1978 → 2088
    CUB; CUB domain
    pfam12947
    Location:353 → 387
    EGF_3; EGF domain
    cl00049
    Location:1048 → 1157
    CUB; CUB domain; extracellular domain; present in proteins mostly known to be involved in development; not found in prokaryotes, plants and yeast.

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    16842423..17148343 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054366803.1 → XP_054222778.1  cubilin isoform X2

  2. XM_054366802.1 → XP_054222777.1  cubilin isoform X1

  3. XM_054366804.1 → XP_054222779.1  cubilin isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O60494.5 GenPept UniProtKB/Swiss-Prot:O60494

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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Chemical Information
Medical
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