TCN1

transcobalamin 1

Basic information

Region (hg38): 11:59852800-59866489

Links

ENSG00000134827 ∙ NCBI:6947 ∙ OMIM:189905 ∙ HGNC:11652 ∙ Uniprot:P20061 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCN1 gene.

• Transcobalamin_I_deficiency (111 variants)
• not_specified (66 variants)
• TCN1-related_disorder (9 variants)
• not_provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001062.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				32	2	34
missense			86	10	1	97
nonsense	2					2
start loss						0
frameshift	3		1			4
splice donor/acceptor (+/-2bp)						0
Total	5	0	87	42	3

Highest pathogenic variant AF is 0.0000638217

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCN1	protein_coding	protein_coding	ENST00000257264	9	13776

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.32e-17	0.00110	125722	0	18	125740	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.08	262	217	1.21	0.0000118	2843
Missense in Polyphen		83	64.849	1.2799		937
Synonymous	0.302	84	87.6	0.959	0.00000534	815
Loss of Function	-0.906	23	18.8	1.23	8.22e-7	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000442	0.0000440
Middle Eastern	0.000326	0.000326
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach.
• Pathway: Vitamin B12 Metabolism;Neutrophil degranulation;Innate Immune System;Immune System;Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.145

Intolerance Scores

• loftool: 0.955
• rvis_EVS: -0.04
• rvis_percentile_EVS: 50.45

Haploinsufficiency Scores

• pHI: 0.0291
• hipred: N
• hipred_score: 0.228
• ghis: 0.408

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.00706

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: cobalt ion transport;cobalamin metabolic process;cobalamin transport;neutrophil degranulation
• Cellular component: extracellular region;extracellular space;specific granule lumen;tertiary granule lumen
• Molecular function: cobalamin binding