CBLIF cobalamin binding intrinsic factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: CBLIFprovided by HGNC
Official Full Name: cobalamin binding intrinsic factorprovided by HGNC
Primary source: HGNC:HGNC:4268
See related: Ensembl:ENSG00000134812 MIM:609342; AllianceGenome:HGNC:4268
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: IF; GIF; INF; IFMH; TCN3
Summary: This gene is a member of the cobalamin transport protein family. It encodes a glycoprotein secreted by parietal cells of the gastric mucosa and is required for adequate absorption of vitamin B12. Vitamin B12 is necessary for erythrocyte maturation and mutations in this gene may lead to congenital pernicious anemia. [provided by RefSeq, Jul 2008]
Annotation information: Note: GIF (Gene ID: 2694) and MT3 (Gene ID: 4504) share the GIF symbol/alias in common. GIF is a widely used alternative name for metallothionein 3 (MT3), which can be confused with the official symbol for GIF (gastric intrinsic factor, GeneID 2694). [01 Jun 2018]
Expression: Restricted expression toward stomach (RPKM 444.5) See more
Orthologs: all
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Genomic context

Location:: 11q12.1

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (59829273..59845499, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (59780568..59796806, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (59596746..59612972, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

Pancytopenia and megaloblastic erythropoiesis reveal a novel GIF mutation.
Title: Pancytopenia and megaloblastic erythropoiesis reveal a novel GIF mutation.
The gastric intrinsic factor (GIF) 290C heterozygous/fucosyltransferase 2 (secretor status included) protein (FUT2) rs601338 secretor variant combined genotype was indicated in 6 of the 37 neural tube defects (NTDs) fetuses.
Title: Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects.
the present findings reveal that High-altitude polycythemia -induced gastric mucosal lesion inspires the protection responses by up-regulating APOA4 and APOC3, and down-regulating GIF.
Title: Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury.
study reports that FUT2 secretor variant influences GIF secretion in B12 deficient cases bearing GIF heterozygous mutations, in absence of H. pylori related gastritis
Title: Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant.
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.
Title: Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns.
Acute lymphoblastic leukemia and vitamin B12 deficiency secondary to a gastric intrinsic factor gene mutation
Title: Acute lymphoblastic leukemia and vitamin B12 deficiency secondary to a gastric intrinsic factor gene mutation.
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk.
crystal structure of the complex between IF-Cbl and the cubilin IF-Cbl-binding-region (CUB(5-8)) determined at 3.3 A resolution
Title: Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes.
a specific GIF mutation to be responsible for all Juvenile cobalamin deficiency cases of West-African origin so far was identified
Title: Juvenile cobalamin deficiency in individuals of African ancestry is caused by a founder mutation in the intrinsic factor gene GIF.
The Q5R mutation of the intrinsic factor gene predisposes to adult-onset pernicious anemia & other causes of low vitamin B12. In this mutation, intrinsic factor secretion is preserved but B12 absorption may be impaired.
Title: Role of (Glu --> Arg, Q5R) mutation of the intrinsic factor in pernicious anemia and other causes of low vitamin B12.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hereditary intrinsic factor deficiency MedGen: C1394891 OMIM: 261000 GeneReviews: Not available	Compare labs

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

SHGC-35409 (e-PCR)
- UniSTS:73994

GDB:197843 (e-PCR)
- UniSTS:155962

GIF (e-PCR)
- UniSTS:9868

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cargo receptor ligand activity	EXP Inferred from Experiment more info	PubMed
enables cobalamin binding	IBA Inferred from Biological aspect of Ancestor more info
enables cobalamin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cobalamin transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in cobalamin transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cobalamin transport	TAS Traceable Author Statement more info
involved_in cobalt ion transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal lumen	TAS Traceable Author Statement more info
located_in microvillus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: cobalamin binding intrinsic factor

Names: gastric intrinsic factor (vitamin B synthesis); intrinsic factor

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_008120.1 RefSeqGene

Range

5003..21229

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005142.3 → NP_005133.2 cobalamin binding intrinsic factor precursor

See identical proteins and their annotated locations for NP_005133.2

Status: REVIEWED

Source sequence(s)

BC037958

Consensus CDS

CCDS7977.1

UniProtKB/Swiss-Prot

B2RAN8, B4DVZ1, P27352

Related

ENSP00000257248.2, ENST00000257248.3

Conserved Domains (2) summary

pfam01122
Location:24 → 306

Cobalamin_bind; Eukaryotic cobalamin-binding protein

pfam14478
Location:341 → 415

DUF4430; Domain of unknown function (DUF4430)

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_000011.10 Reference GRCh38.p14 Primary Assembly

Range

59829273..59845499 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011544939.4 → XP_011543241.1 cobalamin binding intrinsic factor isoform X1

Conserved Domains (2) summary

pfam01122
Location:8 → 293

Cobalamin_bind; Eukaryotic cobalamin-binding protein

pfam14478
Location:326 → 401

DUF4430; Domain of unknown function (DUF4430)