TCN1

Summary

TCN1 (transcobalamin 1, HGNC:11652) is a protein-coding gene on chromosome 11q12.1, encoding Transcobalamin-1 (P20061). Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach.

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.

Source: NCBI Gene 6947 — RefSeq curated summary.

At a glance

• Gene–disease (curated): transcobalamin I deficiency (Moderate, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 183 total — 7 pathogenic
• MANE Select transcript: NM_001062

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11652
Approved symbol	TCN1
Name	transcobalamin 1
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	TCI, TC1
Ensembl gene	ENSG00000134827
Ensembl biotype	protein_coding
OMIM	189905
Entrez	6947

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding_CDS_not_defined, 1 protein_coding, 1 retained_intron

ENST00000257264, ENST00000529251, ENST00000532419, ENST00000533734, ENST00000534531

RefSeq mRNA: 1 — MANE Select: NM_001062 NM_001062

CCDS: CCDS7978

Canonical transcript exons

ENST00000257264 — 9 exons

Exon	Start	End
ENSE00000719474	59855869	59856058
ENSE00000916278	59854652	59854835
ENSE00000916283	59866392	59866487
ENSE00003496813	59859077	59859267
ENSE00003531465	59862582	59862722
ENSE00003620737	59861527	59861682
ENSE00003622094	59853203	59853321
ENSE00003645799	59852808	59853036
ENSE00003663791	59863907	59864086

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 99.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.7832 / max 1633.5219, expressed in 166 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119884	4.7832	166

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.42	gold quality
trachea	UBERON:0003126	99.24	gold quality
parotid gland	UBERON:0001831	98.98	gold quality
nasal cavity mucosa	UBERON:0001826	98.61	gold quality
gall bladder	UBERON:0002110	98.46	gold quality
bone marrow	UBERON:0002371	97.50	gold quality
bone marrow cell	CL:0002092	96.39	gold quality
nasal cavity epithelium	UBERON:0005384	95.98	gold quality
saliva-secreting gland	UBERON:0001044	95.82	gold quality
trabecular bone tissue	UBERON:0002483	95.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.27	gold quality
minor salivary gland	UBERON:0001830	94.90	gold quality
epithelial cell of pancreas	CL:0000083	92.22	gold quality
pylorus	UBERON:0001166	90.65	gold quality
mouth mucosa	UBERON:0003729	88.48	gold quality
islet of Langerhans	UBERON:0000006	87.93	gold quality
cardia of stomach	UBERON:0001162	85.66	gold quality
cervix squamous epithelium	UBERON:0006922	85.56	silver quality
esophagus mucosa	UBERON:0002469	85.26	gold quality
esophagus squamous epithelium	UBERON:0006920	83.44	gold quality
blood	UBERON:0000178	83.20	gold quality
epithelium of esophagus	UBERON:0001976	82.64	gold quality
lower esophagus mucosa	UBERON:0035834	80.70	gold quality
mammalian vulva	UBERON:0000997	79.99	gold quality
cervix epithelium	UBERON:0004801	79.29	gold quality
body of stomach	UBERON:0001161	78.24	gold quality
stomach	UBERON:0000945	77.92	gold quality
oral cavity	UBERON:0000167	77.78	gold quality
mononuclear cell	CL:0000842	77.35	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	780.18
E-CURD-114	yes	660.71
E-HCAD-1	yes	16.29
E-MTAB-9801	yes	9.03
E-CURD-11	no	136.03
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting TCN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-1246	98.54	66.21	959

Literature-anchored findings (GeneRIF, showing 19)

• Comparative analysis of cobalamin binding kinetics (PMID:11788601)
• No association between the MTHFR A1298C and transcobalamin C776G genetic polymorphisms and hyperhomocysteinemia in thrombotic disease. (PMID:12590948)
• interactions of COBALAMIN BINDING proteins with a number of ligands (PMID:17487979)
• two novel mutations, each causing a premature stop codon - a genetic basis for TC I deficiency (PMID:19686235)
• Maternal folate-related polymorphisms studied here (CBS, MTR, RFC-1, and TC) have no influence on trisomy 21 susceptibility in subjects of Brazilian population.v (PMID:19729796)
• Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade, stromal hypercellularity, mitotic activity and microscopic borders. (PMID:21574054)
• Elevated concentrations of B(12) found in autoimmune lymphoproliferative syndrome patients were due to increased lymphocyte expression of haptocorrin. (PMID:22306884)
• comparison of human and rainbow trout cobalamin-binding protein (PMID:22872637)
• TCN1 gene expression implicates disease progression in patient with middle ear cholesteatoma. (PMID:23670528)
• Structural basis for universal corrinoid recognition by the cobalamin transport protein haptocorrin. (PMID:23846701)
• Levels of holotranscobalamin are decreased patients with cobalamin deficiency. (PMID:24057896)
• The variant rs526934 from the TCN1 gene was associated with an increased risk of developing gastric cancer. (PMID:26959381)
• Higher placental TC protein abundance was associated with higher cord blood vitamin B12 concentrations, suggesting a potential role in vitamin B12 transport to the fetus. (PMID:27577703)
• This study reports a novel association between the African ancestry-specific loss-of-function variant TCN1-rs34530014 and lower Vitamin B12 concentration. (PMID:29764838)
• Clinicopathological Analysis and Prognostic Assessment of Transcobalamin I (TCN1) in Patients with Colorectal Tumors. (PMID:32753569)
• Clinicopathological Analysis and Prognostic Assessment of TCN1 in Patients with Gastric Cancer. (PMID:34549663)
• TCN1 Deficiency Inhibits the Malignancy of Colorectal Cancer Cells by Regulating the ITGB4 Pathway. (PMID:35686504)
• Reference intervals and stability of haptocorrin and holotranscobalamin in Danish children and elderly. (PMID:37209861)
• TCN1 Expression Is Increased in Asthma. (PMID:37586352)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	CG3556	FBGN0029708

Paralogs (2): CBLIF (ENSG00000134812), TCN2 (ENSG00000185339)

Protein

Protein identifiers

Transcobalamin-1 — P20061 (reviewed: P20061)

Alternative names: Haptocorrin, Protein R, Transcobalamin I

All UniProt accessions (1): P20061

UniProt curated annotations — full annotation on UniProt →

Function. Binds vitamin B12 with femtomolar affinity and protects it from the acidic environment of the stomach.

Subcellular location. Secreted.

Tissue specificity. Produced by the salivary glands of the oral cavity, in response to ingestion of food. Major constituent of secondary granules in neutrophils.

Post-translational modifications. Contains about 30% carbohydrates.

Similarity. Belongs to the eukaryotic cobalamin transport proteins family.

RefSeq proteins (1): NP_001053* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002157	Cbl-bd_prot	Family
IPR027954	Transcobalamin-like_C	Domain
IPR051588	Cobalamin_Transport	Family

Pfam: PF01122, PF14478

UniProt features (63 total): helix 21, binding site 8, glycosylation site 8, strand 7, turn 7, disulfide bond 4, region of interest 3, sequence variant 2, signal peptide 1, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4KKI	X-RAY DIFFRACTION	2.35
4KKJ	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20061-F1	89.20	0.73

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 402–404; 411; 433; 142–146; 186; 240; 289; 385–386

Disulfide bonds (4): 26–265, 105–308, 155–197, 388–393

Glycosylation sites (8): 160, 216, 316, 337, 343, 349, 354, 369

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9758881	Uptake of dietary cobalamins into enterocytes
R-HSA-9758890	Transport of RCbl within the body
R-HSA-1430728	Metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-196741	Cobalamin (Cbl, vitamin B12) transport and metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 114 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_TRANSITION_METAL_ION_TRANSPORT, STOSSI_RESPONSE_TO_ESTRADIOL, GOBP_MONOATOMIC_CATION_TRANSPORT, MODULE_120, GOBP_VITAMIN_TRANSPORT, HOOI_ST7_TARGETS_DN, SESTO_RESPONSE_TO_UV_C7, SENESE_HDAC1_TARGETS_UP, MODULE_175, MODULE_6, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, BECKER_TAMOXIFEN_RESISTANCE_DN

GO Biological Process (3): cobalt ion transport (GO:0006824), cobalamin transport (GO:0015889), monoatomic ion transport (GO:0006811)

GO Molecular Function (4): cobalamin binding (GO:0031419), molecular sequestering activity (GO:0140313), cargo receptor ligand activity (GO:0140355), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), specific granule lumen (GO:0035580), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Cobalamin (Cbl, vitamin B12) transport and metabolism	2
Innate Immune System	1
Immune System	1
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion transport	1
monoatomic cation transmembrane transport	1
vitamin transport	1
nitrogen compound transport	1
transport	1
vitamin binding	1
tetrapyrrole binding	1
heterocyclic compound binding	1
molecular_function	1
protein binding	1
binding	1
cellular anatomical structure	1
secretory granule lumen	1
specific granule	1
intracellular organelle lumen	1
tertiary granule	1

Protein interactions and networks

STRING

820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCN1	CBL	P22681	911
TCN1	LTF	P02788	818
TCN1	MMP8	P22894	742
TCN1	CD320	Q9NPF0	697
TCN1	H7C0V5	H7C0V5	689
TCN1	ANKHD1	Q8IWZ3	685
TCN1	MS4A2	Q01362	676
TCN1	CUBN	O60494	671
TCN1	DCAF1	Q9Y4B6	662
TCN1	MTR	Q99707	621
TCN1	MMP7	P09237	618
TCN1	LMBRD1	Q9NUN5	593
TCN1	AMN	Q9BXJ7	584
TCN1	OLFM4	Q6UX06	569
TCN1	LCN2	P30150	555

IntAct

14 interactions, top by confidence:

A	B	Type	Score
TCN1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
Ikbip	LTF	psi-mi:“MI:0915”(physical association)	0.400
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
EBF2	LILRA5	psi-mi:“MI:0914”(association)	0.350
ITLN2	IGLC7	psi-mi:“MI:0914”(association)	0.350
SFXN4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
TIMM10	IGLL5	psi-mi:“MI:0914”(association)	0.350
RSRP1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): TCN1 (Affinity Capture-MS), TCN1 (Affinity Capture-MS), TCN1 (Affinity Capture-MS), TCN1 (Affinity Capture-MS), TCN1 (Affinity Capture-MS), TCN1 (Affinity Capture-MS), TCN1 (Affinity Capture-MS), TCN1 (Affinity Capture-MS), TCN1 (Co-fractionation), TCN1 (Affinity Capture-MS), TCN1 (Reconstituted Complex)

ESM2 similar proteins: A7MCS3, B5DFM7, E9Q9F6, O04195, O88968, O93360, O93566, P04095, P04768, P07064, P08899, P09538, P0DP43, P10607, P12402, P12856, P17630, P20061, P34744, P46555, P81134, Q02745, Q07081, Q07221, Q0IHC5, Q0VBN2, Q10351, Q11200, Q11201, Q3KQ18, Q3TT99, Q3UST5, Q5BKJ7, Q66J01, Q6W3E5, Q765H6, Q8CGZ9, Q8CJ42, Q91221, Q91222

Diamond homologs: P17267, P20061, P27352, P52787, Q5XWD5, P17630, P20062, Q5REL7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

183 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	0
Uncertain significance	95
Likely benign	64
Benign	11

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1459208	NM_001062.4(TCN1):c.69C>A (p.Cys23Ter)	Pathogenic
2745906	NM_001062.4(TCN1):c.82del (p.Glu27_Val28insTer)	Pathogenic
2918494	NM_001062.4(TCN1):c.524_530del (p.Lys175fs)	Pathogenic
3665609	NM_001062.4(TCN1):c.217C>T (p.Gln73Ter)	Pathogenic
4742884	NM_001062.4(TCN1):c.455del (p.Leu152fs)	Pathogenic
4762049	NM_001062.4(TCN1):c.229C>T (p.Gln77Ter)	Pathogenic
568555	NM_001062.4(TCN1):c.26del (p.Leu9fs)	Pathogenic

SpliceAI

852 predictions. Top by Δscore:

Variant	Effect	Δscore
11:59853034:CTC:C	acceptor_gain	1.0000
11:59853037:C:CA	acceptor_loss	1.0000
11:59853322:C:CC	acceptor_gain	1.0000
11:59854832:TTACC:T	acceptor_loss	1.0000
11:59854833:TACC:T	acceptor_loss	1.0000
11:59854835:CCT:C	acceptor_loss	1.0000
11:59854836:C:G	acceptor_loss	1.0000
11:59854837:T:C	acceptor_loss	1.0000
11:59859072:CTTA:C	donor_loss	1.0000
11:59859073:TTA:T	donor_loss	1.0000
11:59859074:TACCT:T	donor_loss	1.0000
11:59859075:A:C	donor_loss	1.0000
11:59859076:C:CT	donor_loss	1.0000
11:59861678:TGCTT:T	acceptor_gain	1.0000
11:59861680:CTT:C	acceptor_gain	1.0000
11:59861681:TT:T	acceptor_gain	1.0000
11:59861682:TCTAG:T	acceptor_loss	1.0000
11:59861683:C:CC	acceptor_gain	1.0000
11:59861684:T:A	acceptor_loss	1.0000
11:59862576:TCTTA:T	donor_loss	1.0000
11:59862577:CTTAC:C	donor_loss	1.0000
11:59862578:TTA:T	donor_loss	1.0000
11:59862579:TACC:T	donor_loss	1.0000
11:59862580:A:AC	donor_gain	1.0000
11:59862580:AC:A	donor_gain	1.0000
11:59862580:ACCCA:A	donor_loss	1.0000
11:59862581:C:CC	donor_gain	1.0000
11:59862581:C:G	donor_loss	1.0000
11:59862581:CC:C	donor_gain	1.0000
11:59862581:CCCAT:C	donor_gain	1.0000

AlphaMissense

2854 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:59861639:G:C	S148R	0.977
11:59861639:G:T	S148R	0.977
11:59861641:T:G	S148R	0.977
11:59853318:G:C	F375L	0.975
11:59853318:G:T	F375L	0.975
11:59853320:A:G	F375L	0.975
11:59855963:G:C	F281L	0.971
11:59855963:G:T	F281L	0.971
11:59855965:A:G	F281L	0.971
11:59859085:C:G	A247P	0.966
11:59859233:A:C	C197W	0.966
11:59859095:G:C	S243R	0.965
11:59859095:G:T	S243R	0.965
11:59859097:T:G	S243R	0.965
11:59859240:A:G	L195P	0.961
11:59859259:C:G	A189P	0.960
11:59856058:C:G	A250P	0.957
11:59859235:A:G	C197R	0.957
11:59853237:C:A	W402C	0.956
11:59853237:C:G	W402C	0.956
11:59861534:G:C	F183L	0.952
11:59861534:G:T	F183L	0.952
11:59861536:A:G	F183L	0.952
11:59853018:A:T	V420D	0.951
11:59853239:A:G	W402R	0.951
11:59853239:A:T	W402R	0.951
11:59856017:C:A	W263C	0.948
11:59856017:C:G	W263C	0.948
11:59859253:C:G	A191P	0.948
11:59854654:A:C	F373L	0.944

dbSNP variants (sampled 300 via entrez): RS1000094649 (11:59859211 C>A,T), RS1000386782 (11:59863292 T>C), RS1000766124 (11:59856150 C>A), RS1001192710 (11:59858071 G>A), RS1001332915 (11:59859484 T>C), RS1001478340 (11:59859807 T>C), RS1002483400 (11:59854229 A>C), RS1002657126 (11:59860816 T>C), RS1002986037 (11:59864799 G>A), RS1003188010 (11:59862748 A>G,T), RS1003208753 (11:59861138 G>A,C), RS1003263759 (11:59864383 G>C), RS1003338671 (11:59856325 C>T), RS1003474868 (11:59856633 A>G), RS1003793407 (11:59857362 A>G)

Disease associations

OMIM: gene MIM:189905 | disease phenotypes: MIM:193090

GenCC curated gene-disease

Disease	Classification	Inheritance
transcobalamin I deficiency	Moderate	Autosomal recessive

Mondo (1): transcobalamin I deficiency (MONDO:0008659)

Orphanet (1): Transcobalamin I deficiency (Orphanet:2967)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000358_5	Folate pathway vitamin levels	2.000000e-06
GCST000483_5	Folate pathway vitamin levels	2.000000e-10
GCST002559_5	Vitamin B levels in ischemic stroke	5.000000e-11
GCST004161_2	Vitamin B12 levels	4.000000e-08
GCST006585_947	Blood protein levels	6.000000e-26

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004620	vitamin B12 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562798	Transcobalamin I Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Cadmium Chloride	increases abundance, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
kojic acid	decreases expression	1
sodium arsenite	increases expression	1
abrine	decreases expression	1
NSC 689534	decreases expression, affects binding	1
trametinib	decreases expression, affects cotreatment	1
NVP-BKM120	decreases expression, affects cotreatment	1
Temozolomide	increases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Amphotericin B	decreases expression	1
Arbutin	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects binding, decreases expression	1
Nickel	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression, increases abundance	1
Tetrachlorodibenzodioxin	increases expression	1
Zidovudine	affects cotreatment, increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.