CBLIF

cobalamin binding intrinsic factor

Basic information

Region (hg38): 11:59829272-59845499

Previous symbols: [ "GIF" ]

Links

ENSG00000134812 ∙ NCBI:2694 ∙ OMIM:609342 ∙ HGNC:4268 ∙ Uniprot:P27352 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary intrinsic factor deficiency (Supportive), mode of inheritance: AR
• hereditary intrinsic factor deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intrinsic factor deficiency	AR	Gastrointestinal	Individuals typically present in infancy (though presentations at much later ages have been reported) with pernicious (megaloblastic) anemia, and vitamin B12 administration can be effective	Gastrointestinal; Hematologic	2071148; 14695536; 14576042; 15738392; 20408840; 22929189; 23402911; 23430489
Digenic disease (with FUT2 variants) has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CBLIF gene.

• Hereditary intrinsic factor deficiency (105 variants)
• not provided (21 variants)
• Inborn genetic diseases (3 variants)
• Intrinsic factor deficiency, congenital, susceptibility to (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CBLIF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	16	3	20
missense		1	42	4	4	51
nonsense	1		1			2
start loss						0
frameshift	1		1			2
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)	1	2				3
splice region			4	3	1	8
non coding			4	8	8	20
Total	3	3	50	29	15

Highest pathogenic variant AF is 0.000230

Variants in CBLIF

This is a list of pathogenic ClinVar variants found in the CBLIF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-59829397-C-T		Hereditary intrinsic factor deficiency	Uncertain significance (Jan 13, 2018)
11-59829428-A-C		Hereditary intrinsic factor deficiency	Uncertain significance (Jan 13, 2018)
11-59829508-G-A		Hereditary intrinsic factor deficiency	Likely benign (Sep 10, 2018)
11-59829517-G-A		Hereditary intrinsic factor deficiency	Likely benign (Dec 18, 2023)
11-59829517-G-C		Hereditary intrinsic factor deficiency • not specified	Uncertain significance (Jul 08, 2022)
11-59829527-G-C		Hereditary intrinsic factor deficiency	Uncertain significance (Dec 26, 2020)
11-59831479-TTA-T			Benign (Jun 19, 2021)
11-59831479-T-TTA			Benign (Jun 19, 2021)
11-59831671-C-T		Hereditary intrinsic factor deficiency	Likely benign (Feb 03, 2022)
11-59831680-T-A		Hereditary intrinsic factor deficiency	Uncertain significance (Aug 08, 2020)
11-59831688-AG-A		Hereditary intrinsic factor deficiency	Uncertain significance (May 04, 2018)
11-59831690-G-A		Hereditary intrinsic factor deficiency	Uncertain significance (Jan 13, 2018)
11-59831694-T-TA		Hereditary intrinsic factor deficiency	Pathogenic (Mar 15, 2005)
11-59831707-A-G		Hereditary intrinsic factor deficiency	Uncertain significance (Jun 26, 2018)
11-59831732-C-T		Hereditary intrinsic factor deficiency	Benign/Likely benign (Jan 12, 2024)
11-59831740-G-A		Hereditary intrinsic factor deficiency • not specified	Uncertain significance (Jan 26, 2022)
11-59831741-C-T		Hereditary intrinsic factor deficiency • not specified	Uncertain significance (Jan 03, 2024)
11-59831762-C-G		not specified	Uncertain significance (Aug 30, 2021)
11-59831762-C-T		Hereditary intrinsic factor deficiency • not specified	Uncertain significance (Aug 02, 2023)
11-59831763-G-A		Hereditary intrinsic factor deficiency	Uncertain significance (Jan 13, 2018)
11-59831775-A-T			Likely benign (Feb 09, 2018)
11-59831778-T-C		Hereditary intrinsic factor deficiency	Likely benign (Dec 05, 2022)
11-59831783-T-C		Hereditary intrinsic factor deficiency • not specified	Uncertain significance (Oct 19, 2022)
11-59831798-T-TA		Hereditary intrinsic factor deficiency	Likely benign (Apr 14, 2020)
11-59831799-A-G		Hereditary intrinsic factor deficiency • CBLIF-related disorder	Conflicting classifications of pathogenicity (Sep 16, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CBLIF	protein_coding	protein_coding	ENST00000257248	9	16234

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000249	0.984	125672	0	75	125747	0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.358	205	220	0.932	0.0000116	2732
Missense in Polyphen		44	56.774	0.77501		759
Synonymous	0.0952	85	86.1	0.987	0.00000505	831
Loss of Function	2.14	9	19.1	0.471	9.27e-7	225

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00108	0.00108
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000352	0.000352
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the GIF-cobalamin complex is internalized via receptor-mediated endocytosis.

Recessive Scores

• pRec: 0.320

Intolerance Scores

• rvis_EVS: 0.69
• rvis_percentile_EVS: 85.18

Haploinsufficiency Scores

• pHI: 0.0836
• hipred: Y
• hipred_score: 0.560

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Gif
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; liver/biliary system phenotype; immune system phenotype