TCN2

transcobalamin 2

Basic information

Region (hg38): 22:30607003-30627271

Links

ENSG00000185339

∙ NCBI:6948 ∙ OMIM:613441 ∙ HGNC:11653 ∙ Uniprot:P20062 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

transcobalamin II deficiency (Definitive), mode of inheritance: AR
transcobalamin II deficiency (Strong), mode of inheritance: AR
transcobalamin II deficiency (Supportive), mode of inheritance: AR
transcobalamin II deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Transcobalamin II deficiency	AR	Allergy/Immunology/Infectious; Biochemical	The condition can include neurocognitive impairment, hematologic anomalies (eg, anemia, panyctopenia), susceptibility to recurrent and severe infections, and gastrointestinal sequelae, and cobalamin treatment can result in prevention and/or clinical improvement, including related to developmental parameters; Awareness of immunodeficiency may allow prompt treatment of infections	Allergy/Immunology/Infectious; Biochemical; Gastrointestinal; Hematologic; Neurologic	5096637; 4138209; 128427; 3143215; 309761; 1743216; 7849710; 19373259

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TCN2 gene.

Transcobalamin_II_deficiency (616 variants)
Inborn_genetic_diseases (78 variants)
not_provided (47 variants)
TCN2-related_disorder (17 variants)
not_specified (5 variants)
Pancytopenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TCN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000355.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		4 clinvar	189 clinvar	3 clinvar	197
missense		1 clinvar	213 clinvar	19 clinvar	4 clinvar	237
nonsense	12 clinvar	4 clinvar	2 clinvar			18
start loss	1					1
frameshift	25 clinvar	8 clinvar	1 clinvar			34
splice donor/acceptor (+/-2bp)	4 clinvar	8 clinvar				12
Total	43	21	220	208	7

Highest pathogenic variant AF is 0.00029429587

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TCN2	protein_coding	protein_coding	ENST00000215838	9	20441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000105	0.940	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.12	322	231	1.39	0.0000128	2760
Missense in Polyphen		95	73.17	1.2983		965
Synonymous	-4.19	149	96.6	1.54	0.00000543	873
Loss of Function	1.81	13	22.2	0.585	0.00000133	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000756	0.000756
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000369	0.000360
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells. {ECO:0000269|PubMed:8443384}.;
Disease: DISEASE: Transcobalamin II deficiency (TCN2 deficiency) [MIM:275350]: Results in various forms of anemia. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Vitamin digestion and absorption - Homo sapiens (human);Vitamin B12 Metabolism;One Carbon Metabolism;Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

pRec: 0.565

Intolerance Scores

loftool: 0.808
rvis_EVS: 1.93
rvis_percentile_EVS: 97.49

Haploinsufficiency Scores

pHI: 0.211
hipred: Y
hipred_score: 0.542
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.411

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tcn2
Phenotype

Gene ontology

Biological process: cobalt ion transport;cobalamin metabolic process;cobalamin transport
Cellular component: extracellular region;extracellular space;endosome;lysosomal lumen
Molecular function: protein binding;cobalamin binding;metal ion binding