CBLIF

cobalamin binding intrinsic factor

Basic information

Region (hg38): 11:59829273-59845499

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 (120 variants)
not_specified (44 variants)
not_provided (17 variants)
CBLIF-related_disorder (10 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. These statistics are base on transcript: NM_000005142.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	23 clinvar	2 clinvar	28
missense	1 clinvar	2 clinvar	62 clinvar	12 clinvar	3 clinvar	80
nonsense	2 clinvar	1 clinvar	1 clinvar			4
start loss						0
frameshift	3 clinvar	2 clinvar	2 clinvar			7
splice donor/acceptor (+/-2bp)	2 clinvar	2 clinvar				4
Total	8	7	68	35	5

Highest pathogenic variant AF is 0.000256129

Loading clinvar variants...

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

loftool
rvis_EVS: 0.69
rvis_percentile_EVS: 85.18

Haploinsufficiency Scores

pHI: 0.0836
hipred: Y
hipred_score: 0.560
ghis

Essentials

essential_gene_CRISPR
essential_gene_CRISPR2
essential_gene_gene_trap: N
gene_indispensability_pred
gene_indispensability_score

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;