TCN1 (transcobalamin 1)

Gene

• Entrez ID: 6947
• Gene name: Transcobalamin 1
• Gene symbol: TCN1
• Synonyms (NCBI Gene): HC, TC-1, TC1, TCI
• Chromosome: 11
• Chromosome location: 11q12.1
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1209702636	A>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029712	hsa-miR-26b-5p	Microarray	19088304
MIRT2347388	hsa-miR-1246	CLIP-seq
MIRT2347389	hsa-miR-1290	CLIP-seq
MIRT2347390	hsa-miR-1301	CLIP-seq
MIRT2347391	hsa-miR-1305	CLIP-seq
MIRT2347392	hsa-miR-154	CLIP-seq
MIRT2347393	hsa-miR-1587	CLIP-seq
MIRT2347394	hsa-miR-1976	CLIP-seq
MIRT2347395	hsa-miR-2053	CLIP-seq
MIRT2347396	hsa-miR-3065-5p	CLIP-seq
MIRT2347397	hsa-miR-3154	CLIP-seq
MIRT2347398	hsa-miR-3167	CLIP-seq
MIRT2347399	hsa-miR-3179	CLIP-seq
MIRT2347400	hsa-miR-3185	CLIP-seq
MIRT2347401	hsa-miR-3646	CLIP-seq
MIRT2347402	hsa-miR-3668	CLIP-seq
MIRT2347403	hsa-miR-370	CLIP-seq
MIRT2347404	hsa-miR-3910	CLIP-seq
MIRT2347405	hsa-miR-3915	CLIP-seq
MIRT2347406	hsa-miR-3928	CLIP-seq
MIRT2347407	hsa-miR-421	CLIP-seq
MIRT2347408	hsa-miR-4477a	CLIP-seq
MIRT2347409	hsa-miR-4660	CLIP-seq
MIRT2347410	hsa-miR-4674	CLIP-seq
MIRT2347411	hsa-miR-4694-3p	CLIP-seq
MIRT2347412	hsa-miR-4732-5p	CLIP-seq
MIRT2347413	hsa-miR-4764-3p	CLIP-seq
MIRT2347414	hsa-miR-4802-3p	CLIP-seq
MIRT2347415	hsa-miR-491-3p	CLIP-seq
MIRT2347416	hsa-miR-5047	CLIP-seq
MIRT2347417	hsa-miR-561	CLIP-seq
MIRT2347418	hsa-miR-569	CLIP-seq
MIRT2347419	hsa-miR-618	CLIP-seq
MIRT2347420	hsa-miR-876-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	HDA	16502470
GO:0005615	Component	Extracellular space	IBA
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006824	Process	Cobalt ion transport	IEA
GO:0015889	Process	Cobalamin transport	IBA
GO:0015889	Process	Cobalamin transport	IEA
GO:0015889	Process	Cobalamin transport	TAS	2777761
GO:0031419	Function	Cobalamin binding	IBA
GO:0031419	Function	Cobalamin binding	IEA
GO:0035580	Component	Specific granule lumen	TAS
GO:0140313	Function	Molecular sequestering activity	EXP	23846701, 27411955
GO:0140355	Function	Cargo receptor ligand activity	EXP	22547309
GO:1904724	Component	Tertiary granule lumen	TAS

Other IDs

• MIM: 189905
• HGNC: 11652
• e!Ensembl: ENSG00000134827

Protein

• UniProt ID: P20061
• Protein name: Transcobalamin-1 (TC-1) (Haptocorrin) (HC) (Protein R) (Transcobalamin I) (TC I) (TCI)
• Protein function: Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach.
• PDB: 4KKI, 4KKJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01122	Cobalamin_bind	8 → 329	Eukaryotic cobalamin-binding protein	Family
  PF14478	DUF4430	355 → 432	Domain of unknown function (DUF4430)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Produced by the salivary glands of the oral cavity, in response to ingestion of food. Major constituent of secondary granules in neutrophils. {ECO:0000269|PubMed:2777761}.
• Sequence:

  MRQSHQLPLVGLLLFSFIPSQLCEICEVSEENYIRLKPLLNTMIQSNYNRGTSAVNVVLS
  LKLVGIQIQTLMQKMIQQIKYNVKSRLSDVSSGELALIILALGVCRNAEENLIYDYHLID
  KLENKFQAEIENMEAHNGTPLTNYYQLSLDVLALCLFNGNYSTAEVVNHFTPENKNYYFG
  SQFSVDTGAMAVLALTCVKKSLINGQIKADEGSLKNISIYTKSLVEKILSEKKENGLIGN
  TFSTGEAMQALFVSSDYYNENDWNCQQTLNTVLTEISQGAFSNPNAAAQVLPALMGKTFL
  DINKDSSCVSASGNFNISADEPITVTPPDSQSYISVNYSVRINETYFTNVTVLNGSVFLS
  VMEKAQKMNDTIFGFTMEERSWGPYITCIQGLCANNNDRTYWELLSGGEPLSQGAGSYVV
  RNGENLEVRWSKY

• Sequence length: 433

Pathways

KEGG:

Cobalamin transport and metabolism

Reactome:

Cobalamin (Cbl, vitamin B12) transport and metabolism
Neutrophil degranulation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Transcobalamin I deficiency	Pathogenic	rs749820775, rs2495751032, rs767766166, rs1209702636	RCV001949689 RCV003529662 RCV003643458 RCV000688950	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANEMIA, MEGALOBLASTIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEFICIENCY ANEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MEGALOBLASTIC ANEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TCN1-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VITAMIN B DEFICIENCY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VITAMIN B12 DEFICIENCY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VITAMIN DEFICIENCY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Adenocarcinoma of Lung	Associate	35287670, 36793937, 37322027	★☆☆☆☆ Found in Text Mining only
Asthma	Associate	15270853, 28933920	★☆☆☆☆ Found in Text Mining only
Autoimmune Lymphoproliferative Syndrome	Associate	22306884	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Associate	26959381	★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Associate	32626985	★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Associate	35716043	★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Associate	38070204	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Stimulate	32686693	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Associate	32753569	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Associate	34758154	★☆☆☆☆ Found in Text Mining only
Hypoproteinemia	Associate	36275653	★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Associate	26549640	★☆☆☆☆ Found in Text Mining only
Infections	Associate	29079575	★☆☆☆☆ Found in Text Mining only
Leukemia Lymphoma Adult T Cell	Associate	19655254	★☆☆☆☆ Found in Text Mining only
Leukopenia	Associate	36275653	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Associate	36793937	★☆☆☆☆ Found in Text Mining only
Memory Disorders	Associate	30139959	★☆☆☆☆ Found in Text Mining only
Multiple Organ Failure	Associate	37533854	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Associate	37299978	★☆☆☆☆ Found in Text Mining only
Neoplasms	Associate	19655254, 26581891, 35287670	★☆☆☆☆ Found in Text Mining only
Neoplasms	Stimulate	32686693	★☆☆☆☆ Found in Text Mining only
Neurologic Manifestations	Associate	24225433	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Associate	21931799, 26959381	★☆☆☆☆ Found in Text Mining only
Stroke	Associate	32626985	★☆☆☆☆ Found in Text Mining only
Transcobalamin I Deficiency	Associate	19686235	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Tuberculosis Pulmonary	Associate	36275653	★☆☆☆☆ Found in Text Mining only