CBLIF (cobalamin binding intrinsic factor)

Gene

• Entrez ID: 2694
• Gene name: Cobalamin binding intrinsic factor
• Gene symbol: CBLIF
• Synonyms (NCBI Gene): GIF, IF, IFMH, INF, TCN3
• Chromosome: 11
• Chromosome location: 11q12.1
• 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 mut

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs35211634	T>C	Risk-factor, benign	Coding sequence variant, missense variant
rs121434322	G>A,T	Likely-pathogenic, uncertain-significance	Coding sequence variant, stop gained, missense variant
rs144916324	A>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs147785187	C>T	Pathogenic	Splice donor variant
rs765896727	TCAT>-	Pathogenic	Coding sequence variant, frameshift variant
rs1590854624	->A	Pathogenic	Coding sequence variant, frameshift variant
rs1590859406	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1590860794	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1590860877	C>T	Pathogenic	Splice acceptor variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	20237569, 32296183
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	14695536
GO:0005615	Component	Extracellular space	IEA
GO:0005768	Component	Endosome	IDA	8886952
GO:0005902	Component	Microvillus	IDA	8886952
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006824	Process	Cobalt ion transport	IEA
GO:0015889	Process	Cobalamin transport	IBA
GO:0015889	Process	Cobalamin transport	IEA
GO:0015889	Process	Cobalamin transport	IMP	15738392
GO:0015889	Process	Cobalamin transport	TAS
GO:0016324	Component	Apical plasma membrane	IDA	8886952
GO:0031419	Function	Cobalamin binding	IBA
GO:0031419	Function	Cobalamin binding	IDA	14695536
GO:0031419	Function	Cobalamin binding	IEA
GO:0043202	Component	Lysosomal lumen	TAS
GO:0140104	Function	Molecular carrier activity	IEA
GO:0140355	Function	Cargo receptor ligand activity	EXP	17954916
GO:0140355	Function	Cargo receptor ligand activity	IEA

Other IDs

• MIM: 609342
• HGNC: 4268
• e!Ensembl: ENSG00000134812

Protein

• UniProt ID: P27352
• Protein name: Cobalamin binding intrinsic factor (Gastric intrinsic factor) (Intrinsic factor) (IF) (INF)
• Protein function: Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the CBLIF-cobalamin complex is internalized via receptor-mediated endocytosis.
• PDB: 2PMV, 3KQ4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01122	Cobalamin_bind	8 → 309	Eukaryotic cobalamin-binding protein	Family
  PF14478	DUF4430	340 → 416	Domain of unknown function (DUF4430)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Gastric mucosa.
• Sequence:

  MAWFALYLLSLLWATAGTSTQTQSSCSVPSAQEPLVNGIQVLMENSVTSSAYPNPSILIA
  MNLAGAYNLKAQKLLTYQLMSSDNNDLTIGQLGLTIMALTSSCRDPGDKVSILQRQMENW
  APSSPNAEASAFYGPSLAILALCQKNSEATLPIAVRFAKTLLANSSPFNVDTGAMATLAL
  TCMYNKIPVGSEEGYRSLFGQVLKDIVEKISMKIKDNGIIGDIYSTGLAMQALSVTPEPS
  KKEWNCKKTTDMILNEIKQGKFHNPMSIAQILPSLKGKTYLDVPQVTCSPDHEVQPTLPS
  NPGPGPTSASNITVIYTINNQLRGVELLFNETINVSVKSGSVLLVVLEEAQRKNPMFKFE
  TTMTSWGLVVSSINNIAENVNHKTYWQFLSGVTPLNEGVADYIPFNHEHITANFTQY

• Sequence length: 417

Pathways

KEGG:

Vitamin digestion and absorption
Cobalamin transport and metabolism

Reactome:

Cobalamin (Cbl, vitamin B12) transport and metabolism
Defective GIF causes intrinsic factor deficiency
Defective AMN causes hereditary megaloblastic anemia 1
Defective CUBN causes hereditary megaloblastic anemia 1

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Pathogenic	rs147785187	RCV005900945
Hereditary intrinsic factor deficiency	Pathogenic; Likely pathogenic	rs1590860877, rs121434322, rs1590860794, rs1590854624, rs2495712049, rs796064508, rs1213702908, rs1866558759, rs147785187, rs765896727, rs1590859406	RCV000001815 RCV000001816 RCV000001817 RCV000001818 RCV002717322 RCV000190387 RCV003142348 RCV003601172 RCV000688054 RCV000686858 RCV001029986
See cases	Pathogenic	rs147785187	RCV001197357

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
CBLIF-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	rs35867471, rs1302499666, rs761587396, rs146396839, rs150926439, rs150884181, rs144916324, rs11825834, rs759872025, rs370833765	RCV003977881 RCV003921674 RCV003906937 RCV003930291 RCV004757989 RCV003920258 RCV003897693 RCV003918235 RCV003943014 RCV003962960
Cholangiocarcinoma	Benign	rs35867471	RCV005892993
Clear cell carcinoma of kidney	Benign	rs35867471	RCV005892992
Hepatocellular carcinoma	Benign	rs35867471	RCV005892991
Intrinsic factor deficiency, congenital, susceptibility to	Benign	rs35211634	RCV000001812
Uterine corpus endometrial carcinoma	Benign	rs35867471	RCV005892994

Associations from Text Mining
Disease Name	Relationship Type	References
Anemia	Associate	14576042
Coronary Artery Disease	Associate	35263363
Gastritis	Associate	21567190
Intrinsic Factor Deficiency	Associate	14576042, 22929189
Methylmalonic Aciduria and Homocystinuria CblF Type	Associate	14576042, 15738392, 33172407
Neoplastic Syndromes Hereditary	Associate	33172407
Polycythemia	Associate	26485402
Pulmonary Disease Chronic Obstructive	Associate	35263363
Stomach Diseases	Inhibit	26485402