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GeneE
6 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CBLIF
cobalamin binding intrinsic factor
Chromosome 11 Β· 11q12.1
NCBI Gene: 2694Ensembl: ENSG00000134812.8HGNC: HGNC:4268UniProt: P27352
31PubMed Papers
21Diseases
0Drugs
15Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
microvilluscobalamin bindingapical plasma membranecargo receptor ligand activityhereditary intrinsic factor deficiencyCongenital intrinsic factor deficiencyGrΓ€sbeck-Imerslund diseasevitamin B12 deficiency
✦AI Summary

CBLIF (cobalamin binding intrinsic factor) is a glycoprotein that promotes vitamin B12 (cobalamin) absorption in the terminal ileum 1. The protein binds cobalamin in the stomach and facilitates its transfer from haptocorrin after pancreatic trypsin action 1. Following cobalamin binding, the CBLIF-cobalamin complex undergoes receptor-mediated endocytosis via interaction with the CUBN receptor (cubilin), enabling intestinal uptake through a chloroquine-sensitive transcytotic pathway 2. This transport process completes the enterohepatic cycle of cobalamin recirculation 1. CBLIF is synthesized not only in gastric parietal cells but also in other foregut-derived cells, and is secreted basally in the embryonic stomach without sialic acid modification 3. Clinically, mutations in CBLIF cause hereditary intrinsic factor deficiency, leading to cobalamin malabsorption and pernicious anemia. Additionally, polymorphisms in CBLIF and related B12 transport genes (particularly CUBN) have been associated with nonsyndromic cleft lip/palate susceptibility, suggesting roles in embryonic development beyond B12 metabolism 4. Diagnostic assays measure CBLIF activity and anti-IF blocking antibodies in pernicious anemia patients 5.

Sources cited
1
IF binds cobalamin in stomach, transfers from haptocorrin after trypsin action, absorbed in terminal ileum, localizes to gastric parietal cells and other foregut cells
PMID: 8534960
2
IF secreted by embryonic stomach, binds cobalamin, transported across fetal intestine, lacks sialic acid
PMID: 10367779
3
Cobalamin/IF complex uses chloroquine-sensitive transepithelial pathway for intestinal transport
PMID: 11684816
4
B12 transport gene polymorphisms including CBLIF associated with nonsyndromic cleft lip/palate
PMID: 35471549
5
Method for measuring cobalamin-bound IF complex and anti-IF antibodies in pernicious anemia diagnosis
PMID: 3384987
Disease Associationsβ“˜21
hereditary intrinsic factor deficiencyOpen Targets
0.68Moderate
Congenital intrinsic factor deficiencyOpen Targets
0.64Moderate
GrΓ€sbeck-Imerslund diseaseOpen Targets
0.37Weak
vitamin B12 deficiencyOpen Targets
0.35Weak
vitamin B deficiencyOpen Targets
0.35Weak
megaloblastic anemiaOpen Targets
0.35Weak
deficiency anemiaOpen Targets
0.34Weak
lung adenocarcinomaOpen Targets
0.06Suggestive
gastric carcinomaOpen Targets
0.05Suggestive
dehydrated hereditary stomatocytosisOpen Targets
0.05Suggestive
Hemolytic anemia due to red cell pyruvate kinase deficiencyOpen Targets
0.05Suggestive
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.05Suggestive
infectionOpen Targets
0.04Suggestive
gastric non-cardia carcinomaOpen Targets
0.04Suggestive
gastric cardia carcinomaOpen Targets
0.04Suggestive
sideroblastic anemia 3Open Targets
0.04Suggestive
familial pseudohyperkalemiaOpen Targets
0.03Suggestive
Chronic mucocutaneous candidosisOpen Targets
0.03Suggestive
Immunodeficiency by defective expression of HLA class 2Open Targets
0.03Suggestive
Thymic aplasiaOpen Targets
0.03Suggestive
Hereditary intrinsic factor deficiencyUniProt
Pathogenic Variants15
NM_005142.3(CBLIF):c.183_186del (p.Met61fs)Pathogenic
Hereditary intrinsic factor deficiency|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 61
NM_005142.3(CBLIF):c.79+1G>APathogenic
Hereditary intrinsic factor deficiency|not provided|See cases|Acute myeloid leukemia
β˜…β˜…β˜†β˜†2026
NM_005142.3(CBLIF):c.137C>T (p.Ser46Leu)Likely pathogenic
Hereditary intrinsic factor deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 46
NM_005142.3(CBLIF):c.52_56del (p.Thr18fs)Pathogenic
Hereditary intrinsic factor deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 18
NM_005142.3(CBLIF):c.659T>C (p.Ile220Thr)Pathogenic
Hereditary intrinsic factor deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 220
NM_005142.3(CBLIF):c.395_396delinsAA (p.Phe132Ter)Likely pathogenic
Hereditary intrinsic factor deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 132
NM_005142.3(CBLIF):c.67_68del (p.Gln23fs)Likely pathogenic
Hereditary intrinsic factor deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 23
NM_005142.3(CBLIF):c.310C>T (p.Arg104Ter)Pathogenic
Hereditary intrinsic factor deficiency
β˜…β˜†β˜†β˜†2023β†’ Residue 104
NM_005142.3(CBLIF):c.346C>T (p.Gln116Ter)Pathogenic
Hereditary intrinsic factor deficiency|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 116
NM_005142.3(CBLIF):c.370+1G>CLikely pathogenic
Hereditary intrinsic factor deficiency
β˜…β˜†β˜†β˜†2022
NM_005142.3(CBLIF):c.370+83_426delLikely pathogenic
Hereditary intrinsic factor deficiency
β˜…β˜†β˜†β˜†2021
NM_005142.3(CBLIF):c.661G>A (p.Gly221Arg)Likely pathogenic
Hereditary intrinsic factor deficiency
β˜†β˜†β˜†β˜†2019β†’ Residue 221
NM_005142.3(CBLIF):c.1175dup (p.Thr393fs)Pathogenic
Hereditary intrinsic factor deficiency
β˜†β˜†β˜†β˜†2005β†’ Residue 393
NM_005142.3(CBLIF):c.161del (p.Asn54fs)Pathogenic
Hereditary intrinsic factor deficiency
β˜†β˜†β˜†β˜†2005β†’ Residue 54
NM_005142.3(CBLIF):c.80-1G>APathogenic
Hereditary intrinsic factor deficiency
β˜†β˜†β˜†β˜†2005
View on ClinVar β†—
Related Genes
TCN2Shared pathway100%ATP4BProtein interaction88%CBLProtein interaction86%TCN1Protein interaction85%LIPFProtein interaction75%ATP4AProtein interaction73%
Tissue Expression6 tissues
Liver
100%
Ovary
90%
Brain
40%
Lung
40%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CBLIFTCN2ATP4BCBLTCN1LIPFATP4A
PROTEIN STRUCTURE
Preparing viewer…
PDB2PMV Β· 2.60 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.86LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.55 [0.36–0.86]
RankingsWhere CBLIF stands among ~20K protein-coding genes
  • #11,675of 20,598
    Most Researched31
  • #2,478of 5,498
    Most Pathogenic Variants15
  • #7,597of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedCBLIF
Sources retrieved6 papers
Response timeβ€”
πŸ“„ Sources
6β–Ό
1
Vitamin B12 Transport Genes and Nonsyndromic Cleft Lip With or Without Cleft Palate in Chile.
PMID: 35471549
Reprod Sci Β· 2022
1.00
2
Gastric intrinsic factor and its receptor.
PMID: 8534960
Baillieres Clin Haematol Β· 1995
0.83
3
Assimilation of [57Co]-labeled cobalamin in human fetal gastrointestinal xenografts into nude mice.
PMID: 10367779
Pediatr Res Β· 1999
0.67
4
Rapid protein A assay for intrinsic factor and its binding antibody.
PMID: 3384987
J Clin Pathol Β· 1988
0.50
5
Paracellular transport of avidin saturated or not with biotinylated cobalamin through Caco-2 cell epithelium monolayer.
PMID: 11684816
Cell Physiol Biochem Β· 2001
0.33