TCN1

Chr 11

transcobalamin 1

Also known as: HC, TC-1, TC1, TCI

NCBI Gene: 6947 ENSG00000134827 UniProt: P20061

This gene encodes a member of the vitamin B12-binding protein family. This family of proteins, alternatively referred to as R binders, is expressed in various tissues and secretions. This protein is a major constituent of secondary granules in neutrophils and facilitates the transport of cobalamin into cells. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.72

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.72LOEUF

pLI 0.000

Z-score -0.91

OE 1.23 (0.88–1.72)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.08Z-score

OE missense 1.21 (1.09–1.34)

262 obs / 217.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.23 (0.88–1.72)

0≤0.351.4

Missense OE?1.21 (1.09–1.34)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 23 / 18.8Missense obs/exp: 262 / 217.1Syn Z: 0.30

Background carrier burden — how many people carry a rare variant somewhere in TCN1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

569 rare PASS variants

Rare truncating (LoF)

1 in 850

120 rare PASS variants

Rare synonymous (reference)

1 in 150

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TCN1. 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 120	1 in 820
South Asian	~43k	1 in 58	1 in 610
Remaining (unassigned)	~30k	1 in 70	1 in 980
European (Finnish)	~27k	1 in 350	≈ 1 in 8,900
Admixed American	~22k	1 in 85	1 in 270
African / African American	~21k	1 in 96	1 in 1,500
East Asian	~20k	1 in 100	1 in 1,700
Ashkenazi Jewish	~13k	1 in 180	none seen
Middle Eastern	~2,884	1 in 55	1 in 410

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): 9 of 9 coding exons well covered in gnomAD exomes. Genomes: 8 of 9 (exon 6 below).? see exons ↓