CBLIF

protein-coding

cobalamin binding intrinsic factor

Gene 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 mutations in this gene may lead to congenital pernicious anemia. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_005142.3

Inheritance

ClinVar variants

P:16U:73B:46

Top phenotype

Intrinsic factor deficiency

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr11:59,829,273-59,845,499

External References & Databases

Ensembl (ENSG00000134812)

Transcript & Mutation Effects

hg38 • Region Span ~16.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary intrinsic factor deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009852

Submitter: Orphanet

hereditary intrinsic factor deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009852

Submitter: Labcorp Genetics (formerly Invitae)

hereditary intrinsic factor deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009852

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intrinsic factor deficiencyAR

Manifestation: Gastrointestinal; Hematologic

Intervention: Gastrointestinal

Rationale: 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

Comments: Digenic disease (with FUT2 variants) has been described

Refs: 2071148; 14695536; 14576042; 15738392; 20408840; 22929189; 23402911; 23430489

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CBLIF variants in ClinVar

6 Conditions Cataloged

Hereditary intrinsic factor deficiencyTotal: 130

not specifiedTotal: 63

not providedTotal: 23

CBLIF-related disorderTotal: 11

CBLIF & GIF-related disordersTotal: 2

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005142.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	29 clinvar	2 clinvar	35
missense	1 clinvar	3 clinvar	66 clinvar	13 clinvar	2 clinvar	85
nonsense	2 clinvar	1 clinvar	1 clinvar			4
start loss						0
frameshift	4 clinvar	1 clinvar	2 clinvar			7
splice donor/acceptor (+/-2bp)	2 clinvar	2 clinvar				4
Total	9	7	73	42	4	135

Highest pathogenic variant AF is 0.00025612907

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005142.3	RefSeq	NP_005133.2	9	MANE Select
ENST00000257248.3	Ensembl	ENSP00000257248.2	9	MANE Select
ENST00000525058.5	Ensembl	ENSP00000433196.1	1	Standard
XM_011544939.4	RefSeq	XP_011543241.1	9	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257248
Coding exons: 9
Length: 16234
Individuals with no LoFs: 125672
Homozygous LoFs: 0
Heterozygous LoFs: 75
Defined: 125747
p: 0.000298

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.358	205	220	0.932	0.0000116	2732
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.00040	0.00040	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00035	0.00035	rare
South Asian	0.000065	0.000065	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

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

Essentials

Essential (gene trap): N