CBLIF

Chr 11AR

cobalamin binding intrinsic factor

Also known as: GIF, IF, IFMH, INF, TCN3

NCBI Gene: 2694 ENSG00000134812 UniProt: P27352 OMIM: 609342

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intrinsic factor deficiencyMIM #261000

UniProtHereditary intrinsic factor deficiency

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Intrinsic factor deficiency; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.14

OE 0.47 (0.28–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.36Z-score

OE missense 0.93 (0.83–1.05)

205 obs / 219.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.28–0.82)

0≤0.351.4

Missense OE?0.93 (0.83–1.05)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 9 / 19.1Missense obs/exp: 205 / 219.9Syn Z: 0.10

Background carrier burden — how many people carry a rare variant somewhere in CBLIF?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

506 rare PASS variants

Rare truncating (LoF)

1 in 1,200

54 rare PASS variants

Rare synonymous (reference)

1 in 520

196 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CBLIF. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,200
South Asian	~43k	1 in 97	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 78	1 in 1,400
European (Finnish)	~27k	1 in 1,200	≈ 1 in 27,000
Admixed American	~22k	1 in 74	1 in 1,500
African / African American	~21k	1 in 95	1 in 420
East Asian	~20k	1 in 190	1 in 3,300
Ashkenazi Jewish	~13k	1 in 1,500	none seen
Middle Eastern	~2,884	1 in 110	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 6 of 9 coding exons well covered in gnomAD exomes; exons 3, 8, 9 marginal. Genomes: all 9.? see exons ↓