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	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	31738590		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	30403186	Associate	★☆☆☆☆ Found in Text Mining only
Anemia, Megaloblastic	Anemia	CTD_human_DG	4627864		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anxiety Disorders	Anxiety Disorder	BEFREE	29751240		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	Pubtator	15270853, 28933920	Associate	★☆☆☆☆ Found in Text Mining only
Autoimmune Lymphoproliferative Syndrome	Autoimmune lymphoproliferative disorder	Pubtator	22306884	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	28638446		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	26959381	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	31738590		★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Ischemic stroke	Pubtator	32626985	Associate	★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	35716043	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Kidney Diseases	Kidney Disease	BEFREE	29212624		★☆☆☆☆ Found in Text Mining only
Chronic Periodontitis	Periodontitis	BEFREE	23748736, 28114408		★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Ulcerative colitis	Pubtator	38070204	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	24959000, 30906656		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	32686693	Stimulate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	32753569	Associate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	18349696, 29092782		★☆☆☆☆ Found in Text Mining only
Dermatitis, Atopic	Dermatitis	BEFREE	29706020		★☆☆☆☆ Found in Text Mining only
Eczema	Eczema	BEFREE	29706020		★☆☆☆☆ Found in Text Mining only
Elejalde Disease	Hereditary elliptocytosis	Pubtator	30403186	Stimulate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	34758154	Associate	★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune system disease	Pubtator	26549640	Associate	★☆☆☆☆ Found in Text Mining only
liposarcoma	Liposarcoma	BEFREE	20042637		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	28638446		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	36793937	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma, Non-Hodgkin	Non-Hodgkin lymphoma	BEFREE	25384508		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	28638446		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	31738590		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	20852008		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	26959381		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	19029839, 21574054, 31738590		★☆☆☆☆ Found in Text Mining only
Malignant Squamous Cell Neoplasm	Neoplasm	BEFREE	30100732		★☆☆☆☆ Found in Text Mining only
Memory Disorders	Memory disorders	Pubtator	30139959	Associate	★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	18349696, 29092782		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	37299978	Associate	★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	6949616		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	21574054, 28638446, 28666747		★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural Tube Defect	BEFREE	2430743		★☆☆☆☆ Found in Text Mining only
NEUROTICISM	Neuroticism	BEFREE	15108187, 15599377, 19199283, 29102897		★☆☆☆☆ Found in Text Mining only
Neutrophilia (disorder)	Neutrophilia	BEFREE	28933920		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	31738590		★☆☆☆☆ Found in Text Mining only
Oppositional Defiant Disorder	Oppositional Defiant Disorder	BEFREE	17690945		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	20852008		★☆☆☆☆ Found in Text Mining only
Rectal Carcinoma	Rectal Carcinoma	BEFREE	28638446		★☆☆☆☆ Found in Text Mining only
Secondary malignant neoplasm of colon and/or rectum	Colorectal Neoplasms	BEFREE	30906656		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the hypopharynx	Hypopharyngeal Carcinoma	BEFREE	30100732		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	26959381		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	21931799, 26959381	Associate	★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	32626985	Associate	★☆☆☆☆ Found in Text Mining only
Transcobalamin I Deficiency	Transcobalamin deficiency	Pubtator	19686235	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Transcobalamin I Deficiency	Transcobalamin Deficiency	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Transcobalamin II deficiency	Transcobalamin Deficiency	BEFREE	10714245		★☆☆☆☆ Found in Text Mining only
Vitamin B 12 Deficiency	Cobalamin deficiency	BEFREE	19686235, 23183759		★☆☆☆☆ Found in Text Mining only