CUBN cubilin [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

Location:: 10p13

Exon count:: 71

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (16823966..17129811, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (16842423..17148343, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (16865965..17171810, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Polymorphisms in LRP2 and CUBN genes and their association with serum vitamin D levels and sleep apnea.
Title: Polymorphisms in LRP2 and CUBN genes and their association with serum vitamin D levels and sleep apnea.
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.
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?
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.
Clinical and genetic characterization of children with cubilin variants.
Title: Clinical and genetic characterization of children with cubilin variants.
Novel pathogenic variants in CUBN uncouple proteinuria from renal function.
Title: Novel pathogenic variants in CUBN uncouple proteinuria from renal function.
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.
CUBN gene mutations may cause focal segmental glomerulosclerosis (FSGS) in children.
Title: CUBN gene mutations may cause focal segmental glomerulosclerosis (FSGS) in children.
Cubilin, the intrinsic factor-vitamin B12 receptor.
Title: Cubilin, the intrinsic factor-vitamin B12 receptor.
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.

Submit: New GeneRIF Correction See all GeneRIFs (63)

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 EBI GWAS CatalogPubMed
CUBN is a gene locus for albuminuria. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

stSG69827 (e-PCR)
- UniSTS:181801

RH122154 (e-PCR)
- UniSTS:134714

SHGC-107387 (e-PCR)
- UniSTS:170327

SHGC-80852 (e-PCR)
- UniSTS:102502

D1S3698 (e-PCR)
- UniSTS:474276

D22S296 (e-PCR)
- UniSTS:147641

SHGC-144890 (e-PCR)
- UniSTS:172478

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 more info	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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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

NG_008967.1 RefSeqGene

Range

5001..310852

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_540

mRNA and Protein(s)

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

16823966..17129811 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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.
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
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.