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Congenital intrinsic factor deficiency (IFD) is a rare disorder of vitamin B12 (cobalamin) absorption that is characterized by megaloblastic anemia and neurological abnormalities.
Features include always present findings: Reduced haptoglobin level, Malabsorption of Vitamin B12, Increased RBC distribution width, and Decreased circulating vitamin B12 concentration and others; and common findings: Progressive loss of mental abilities (dementia), Specific learning disability, Hyperhomocystinemia, and Recurrent infections and others. 22 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Brain and nerves | 5 | Paresthesia, Progressive loss of mental abilities (dementia), Specific learning disability |
Blood and immune system | 3 | Megaloblastic anemia, Larger than normal red blood cells (increased mean corpuscular volume), Recurrent infections |
Digestive system | 1 | Malabsorption of Vitamin B12 |
Lab test results | 1 | Elevated LDH (tissue damage marker) (increased circulating lactate dehydrogenase concentration) |
Growth and development | 1 | Growth delay |
Muscles | 1 | Atrophy of the spinal cord |
CBLIF encodes cobalamin binding intrinsic factor (417 aa). 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 Highest expression in Stomach (1,431 TPM) and Testis (0.3 TPM).
Hereditary intrinsic factor deficiency is associated with mutations in the CBLIF gene on chromosome 11.
The CBLIF protein participates in Defective CBLIF does not bind Cbl, CUBN:AMN-mediated CBLIF:RCbl uptake and delivery to lysosome, and Unknown lysosomal protease degrades CBLIF:RCbl to release Cbl pathways.
CBLIF is classified as a druggable target (Druggable Genome category) with score 0.0.
Genetic testing for CBLIF is available. Testing is considered confirmatory for diagnosis.
Biomarker and diagnostic research for hereditary intrinsic factor deficiency has been reported in the published literature.
Phenotype severity distribution: 7 always present features, 6 common features.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
1 clinical trial registered. Interventions under study include other interventions. Research is primarily sponsored by academic and government institutions.
9 publications have been identified in PubMed for hereditary intrinsic factor deficiency. Research spans Case Report / Case Series (33%), Review / Meta-Analysis (22%), and Diagnostic / Biomarker (11%).
Boumela N (2026). [PMID: 42131342](https://pubmed.ncbi.nlm.nih.gov/42131342/). *Front Immunol*. [Diagnostic / Biomarker]
Motamarri RSAL (2026). [PMID: 42012420](https://pubmed.ncbi.nlm.nih.gov/42012420/). *Nutr Health*. [Case Report / Case Series]
Singh N (2026). [PMID: 42040682](https://pubmed.ncbi.nlm.nih.gov/42040682/). *Indian J Hematol Blood Transfus*. [Epidemiology / Natural History]
Massironi S (2025). [PMID: 41148791](https://pubmed.ncbi.nlm.nih.gov/41148791/). *Cells*. [Basic Science / Preclinical]
Habeb B (2025). [PMID: 40809655](https://pubmed.ncbi.nlm.nih.gov/40809655/). *Cureus*. [Case Report / Case Series]
Cascetta G (2024). [PMID: 39193325](https://pubmed.ncbi.nlm.nih.gov/39193325/). *Frontiers in pharmacology*. [Review / Meta-Analysis]
Mucha P (2024). [PMID: 39125597](https://pubmed.ncbi.nlm.nih.gov/39125597/). *International journal of molecular sciences*. [Review / Meta-Analysis]
Lacombe V (2024). [PMID: 38797248](https://pubmed.ncbi.nlm.nih.gov/38797248/). *The American journal of clinical nutrition*. [Clinical Trial Publication]
Tsubaki T (2024). [PMID: 39364493](https://pubmed.ncbi.nlm.nih.gov/39364493/). *Cureus*. [Case Report / Case Series]
Data assembled from 7 of 12 sources · Last updated Sep 18, 2026, 7:12 AM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center