CD320

Summary

CD320 (CD320 molecule, HGNC:16692) is a protein-coding gene on chromosome 19p13.2, encoding CD320 antigen (Q9NPF0). Receptor for transcobalamin saturated with cobalamin (TCbl).

This gene encodes the transcobalamin receptor that is expressed at the cell surface. It mediates the cellular uptake of transcobalamin bound cobalamin (vitamin B12), and is involved in B-cell proliferation and immunoglobulin secretion. Mutations in this gene are associated with methylmalonic aciduria. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 51293 — RefSeq curated summary.

At a glance

• Gene–disease (curated): methylmalonic acidemia due to transcobalamin receptor defect (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 237 total
• Phenotypes (HPO): 8
• MANE Select transcript: NM_016579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16692
Approved symbol	CD320
Name	CD320 molecule
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	8D6, 8D6A, TCblR, TCN2R, sCD320, TCII-R
Ensembl gene	ENSG00000167775
Ensembl biotype	protein_coding
OMIM	606475
Entrez	51293

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000301458, ENST00000537716, ENST00000596002, ENST00000596246, ENST00000598299, ENST00000599573, ENST00000874637, ENST00000874638, ENST00000874639, ENST00000874640, ENST00000932616, ENST00000932617, ENST00000932618, ENST00000932619, ENST00000932620, ENST00000932621, ENST00000963189

RefSeq mRNA: 2 — MANE Select: NM_016579 NM_001165895, NM_016579

CCDS: CCDS12198, CCDS54210

Canonical transcript exons

ENST00000301458 — 5 exons

Exon	Start	End
ENSE00001116850	8305031	8305156
ENSE00001116851	8303855	8304088
ENSE00003156927	8308149	8308358
ENSE00003523703	8302777	8302980
ENSE00003617384	8302127	8302605

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.9677 / max 211.2873, expressed in 1746 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178934	31.9677	1746

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.11	gold quality
apex of heart	UBERON:0002098	95.55	gold quality
left testis	UBERON:0004533	94.24	gold quality
right testis	UBERON:0004534	93.87	gold quality
omental fat pad	UBERON:0010414	93.65	gold quality
peritoneum	UBERON:0002358	93.60	gold quality
transverse colon	UBERON:0001157	93.38	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.84	gold quality
spleen	UBERON:0002106	92.83	gold quality
body of stomach	UBERON:0001161	92.64	gold quality
right adrenal gland cortex	UBERON:0035827	92.59	gold quality
right adrenal gland	UBERON:0001233	92.46	gold quality
right lobe of thyroid gland	UBERON:0001119	92.40	gold quality
left adrenal gland	UBERON:0001234	92.24	gold quality
left coronary artery	UBERON:0001626	92.19	gold quality
coronary artery	UBERON:0001621	91.95	gold quality
left adrenal gland cortex	UBERON:0035825	91.89	gold quality
testis	UBERON:0000473	91.83	gold quality
fundus of stomach	UBERON:0001160	91.72	gold quality
thoracic aorta	UBERON:0001515	91.71	gold quality
ascending aorta	UBERON:0001496	91.70	gold quality
body of pancreas	UBERON:0001150	91.57	gold quality
left lobe of thyroid gland	UBERON:0001120	91.48	gold quality
right coronary artery	UBERON:0001625	91.42	gold quality
heart left ventricle	UBERON:0002084	91.38	gold quality
adrenal cortex	UBERON:0001235	91.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.33	gold quality
right atrium auricular region	UBERON:0006631	91.20	gold quality
cardiac ventricle	UBERON:0002082	91.12	gold quality
descending thoracic aorta	UBERON:0002345	91.10	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	2429.38
E-MTAB-10018	yes	463.42
E-GEOD-125970	yes	44.31
E-CURD-46	yes	33.69
E-MTAB-6701	yes	28.65
E-HCAD-10	yes	16.75
E-ANND-3	yes	13.55
E-CURD-10	no	124.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOXA2, JUN, MZF1, RREB1

miRNA regulators (miRDB)

6 targeting CD320, 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-4722-5P	98.46	66.34	1611
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-1204	89.50	65.56	109

Literature-anchored findings (GeneRIF, showing 22)

• This gene encodes a receptor for cellular uptake of transcobalamin-bound vitamin B12. (PMID:18779389)
• Confocal microscopy of tonsil sections revealed co-localization of CD320 with CD19 and CD38 but not with CD3 indicating that germinal center B cells expressed CD320 in addition to follicular dendritic cells. (PMID:19123977)
• Analysis of TCblR/CD320, the gene for the receptor for cellular uptake of transcobalamin-bound cobalamin, identified a homozygous single codon deletion, c.262_264GAG (p.E88del), resulting in the loss of a glutamic acid residue. (PMID:20524213)
• Our data suggest that variation in TCblR plays a role in neural tube defect risk and that these variants may modulate cobalamin metabolism. (PMID:20577008)
• the cell cycle associated expression of TCblR appears to be tightly regulated in synchrony with the proliferative phase of the cell cycle. (PMID:20627121)
• TCblr SNP were associated with omphalocele suggests that disruption of methylation reactions, in which folate, vitamin B12, and homocysteine play critical parts, may be a risk factor for omphalocele. (PMID:22116453)
• Data indicate that only the extracellular region (aa 32-229) of TCblR/CD320 is needed for transcobalamin-cobalamin (TC-Cbl) binding. (PMID:23603833)
• The high urinary concentration and the strong correlation between urinary and serum sCD320 suggests that sCD320 is filtered in the kidney. (PMID:24015289)
• Proliferating cancer cells express measurable levels of TCII and TCII-R. (PMID:24122983)
• Transcobalamin II (TCN2 67A>G and TCN2 776C>G) and transcobalamin II receptor (TCblR 1104C>T) polymorphisms in Korean patients with idiopathic recurrent spontaneous abortion (PMID:24750446)
• Although not significant when corrected for multiple testing, eight single nucleotide polymorphisms (SNPs) in two genes, transcobalamin II (TCN2) and the transcobalamin II-receptor (TCblR), were found to influence several clinical traits of cobalamin deficiency. (PMID:25657319)
• The soluble transcobalamin receptor is present in cerebrospinal fluid and correlates to dementia-related biomarkers tau proteins and amyloid-beta. (PMID:26205293)
• the crystal structure of human holo-transcobalamin (TC) in complex with the extracellular domain of CD320, visualizing the structural basis of the TC-CD320 interaction, is reported. (PMID:27411955)
• There was no significant difference in the expression of soluble csf CD320 between patients and controls. (PMID:28486088)
• It has been proposed that the transcobalamin 2 receptor (TCN2R) is associated with idiopathic recurrent spontaneous abortion (RSA). The findings showed no significant association between TCN2R rs2336573 polymorphisms and the risk/protection of recurrent spontaneous abortion. (PMID:29537328)
• A known pathogenic CD320 variant (c.262_264GAG; p.Glu88del) in methylmalonic aciduria cases. (PMID:29663633)
• In genotype combination analysis, two combinations containing the TCN2 67 polymorphism AG type were associated with RIF risk. Our study showed that the polymorphisms of TCN2 and TCblR are associated with RIF and are potential genetic predisposing factors for RIF among Korean women. (PMID:31123954)
• 3’-UTR Polymorphisms of Vitamin B-Related Genes Are Associated with Osteoporosis and Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women. (PMID:32498429)
• Cellular uptake of vitamin B12: Role and fate of TCblR/CD320, the transcobalamin receptor. (PMID:32898552)
• Intracellular and Tissue Levels of Vitamin B12 in Hepatocytes Are Modulated by CD320 Receptor and TCN2 Transporter. (PMID:33803025)
• Probing the functional consequence and clinical relevance of CD320 p.E88del, a variant in the transcobalamin receptor gene. (PMID:35107211)
• Transcobalamin receptor gene polymorphisms and mutation in an elderly population. (PMID:37202078)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd320	ENSMUSG00000002308
rattus_norvegicus	Ndufa7	ENSRNOG00000006901

Paralogs (1): LDLRAD2 (ENSG00000187942)

Protein

Protein identifiers

CD320 antigen — Q9NPF0 (reviewed: Q9NPF0)

Alternative names: 8D6 antigen, FDC-signaling molecule 8D6, Transcobalamin receptor

All UniProt accessions (3): Q9NPF0, M0R100, M0R1C4

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for transcobalamin saturated with cobalamin (TCbl). Plays an important role in cobalamin uptake. Plasma membrane protein that is expressed on follicular dendritic cells (FDC) and mediates interaction with germinal center B cells. Functions as costimulator to promote B cell responses to antigenic stimuli; promotes B cell differentiation and proliferation. Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC). CD320 augments the proliferation of PC precursors generated by IL-10.

Subunit / interactions. Interacts (via LDL-receptor class A domains) with TCN2.

Subcellular location. Cell membrane.

Tissue specificity. Detected in the germinal center (GC) of lymphoid follicles (at protein level). Expressed abundantly on follicular dendritic cells (FDCs).

Disease relevance. Methylmalonic aciduria, transient, due to transcobalamin receptor defect (MATR) [MIM:613646] An autosomal recessive metabolic condition characterized by moderate methymalonicaciduria, and normal plasma vitamin B12 levels. Serum homocysteine may be increased in some affected individuals. Most cases are clinically asymptomatic. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPF0-1	1	yes
Q9NPF0-2	2

RefSeq proteins (2): NP_001159367, NP_057663* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR023415	LDLR_class-A_CS	Conserved_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR050685	LDLR	Family

Pfam: PF00057

UniProt features (49 total): binding site 12, strand 8, disulfide bond 6, sequence variant 5, helix 4, glycosylation site 3, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7QBF	X-RAY DIFFRACTION	1.85
4ZRP	X-RAY DIFFRACTION	2.1
4ZRQ	X-RAY DIFFRACTION	2.6
7QBG	X-RAY DIFFRACTION	2.69
7QBE	X-RAY DIFFRACTION	3
7QBD	X-RAY DIFFRACTION	4.18

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPF0-F1	64.61	0.14

Antibody-complex structures (SAbDab): 4 — 7QBD, 7QBE, 7QBF, 7QBG

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 (12): 75; 77; 79; 85; 86; 150; 153; 155; 157; 163; 164; 72

Disulfide bonds (6): 54–67, 61–80, 74–89, 132–145, 139–158, 152–167

Glycosylation sites (3): 126, 195, 213

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-3359485	Defective CD320 causes MMATC
R-HSA-9758890	Transport of RCbl within the body
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
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
R-HSA-3296469	Defects in cobalamin (B12) metabolism
R-HSA-3296482	Defects in vitamin and cofactor metabolism
R-HSA-5668914	Diseases of metabolism

MSigDB gene sets: 204 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_B_CELL_ACTIVATION, GOBP_LYMPHOCYTE_COSTIMULATION, GOBP_B_CELL_PROLIFERATION, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_B_CELL_PROLIFERATION, GOBP_REGULATION_OF_VITAMIN_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_LEUKOCYTE_PROLIFERATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13

GO Biological Process (6): cobalamin transport (GO:0015889), regulation of vitamin metabolic process (GO:0030656), positive regulation of B cell proliferation (GO:0030890), B cell costimulation (GO:0031296), signal transduction (GO:0007165), vesicle-mediated transport (GO:0016192)

GO Molecular Function (6): calcium ion binding (GO:0005509), growth factor activity (GO:0008083), cobalamin binding (GO:0031419), cargo receptor activity (GO:0038024), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Defects in cobalamin (B12) metabolism	1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1
Defects in vitamin and cofactor metabolism	1
Diseases of metabolism	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of B cell activation	2
cellular process	2
vitamin transport	1
nitrogen compound transport	1
vitamin metabolic process	1
regulation of small molecule metabolic process	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
lymphocyte costimulation	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transport	1
metal ion binding	1
receptor ligand activity	1
vitamin binding	1
tetrapyrrole binding	1
heterocyclic compound binding	1
molecular_function	1
vesicle-mediated transport	1
molecular adaptor activity	1
binding	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD320	TCN2	P20062	951
CD320	LMBRD1	Q9NUN5	886
CD320	MMAA	Q8IVH4	875
CD320	MMADHC	Q9H3L0	863
CD320	MMAB	Q96EY8	845
CD320	MTR	Q99707	816
CD320	MMUT	P22033	791
CD320	TCN1	P20061	697
CD320	MTRR	Q9UBK8	688
CD320	CUBN	O60494	609
CD320	ABCD4	O14678	600
CD320	MMACHC	Q9Y4U1	596
CD320	CBLIF	P27352	560
CD320	CBL	P22681	546
CD320	AMN	Q9BXJ7	507

IntAct

86 interactions, top by confidence:

A	B	Type	Score
IL2RG	REEP6	psi-mi:“MI:0914”(association)	0.710
TCN2	CD320	psi-mi:“MI:0407”(direct interaction)	0.680
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
CD4	CCDC85C	psi-mi:“MI:0914”(association)	0.530
LTBR	ZNF724	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530
DAAM2	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
ACVR1	BMPR1A	psi-mi:“MI:0914”(association)	0.530
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
XKRX	FAM234B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
TPCN2	AP3B1	psi-mi:“MI:0914”(association)	0.530
TGFBR2	PIK3R2	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530

BioGRID (88): CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS), CD320 (Affinity Capture-MS)

ESM2 similar proteins: A1L0T3, A1L4H1, A6QNY1, D3YZF7, O95428, P28698, P30203, P55068, P55106, P59222, P98162, Q04756, Q14767, Q28019, Q28062, Q28256, Q28343, Q28670, Q3U515, Q4G0T1, Q5F378, Q5HZW5, Q61003, Q61361, Q6H9L7, Q6KF10, Q6PGE4, Q6QNF4, Q7TQH7, Q7Z4F1, Q86T13, Q86VR7, Q86VZ4, Q8BV57, Q8BZE1, Q8CB67, Q8VCP9, Q8WTU2, Q91V98, Q96DN2

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	123
Likely benign	59
Benign	44

Top pathogenic / likely-pathogenic (0)

SpliceAI

992 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8302603:CCG:C	acceptor_gain	1.0000
19:8302604:CGC:C	acceptor_gain	1.0000
19:8302606:C:CC	acceptor_gain	1.0000
19:8302772:CTTAC:C	donor_loss	1.0000
19:8302773:TTA:T	donor_loss	1.0000
19:8302774:TA:T	donor_loss	1.0000
19:8302774:TACCA:T	donor_loss	1.0000
19:8302775:A:AC	donor_gain	1.0000
19:8302775:A:AG	donor_loss	1.0000
19:8302775:A:T	donor_loss	1.0000
19:8302776:C:CC	donor_gain	1.0000
19:8302776:CCAG:C	donor_gain	1.0000
19:8302981:C:CC	acceptor_gain	1.0000
19:8305029:A:AC	donor_gain	1.0000
19:8305030:C:CC	donor_gain	1.0000
19:8305030:C:CT	donor_gain	1.0000
19:8305030:CTGCA:C	donor_gain	1.0000
19:8302411:T:TA	donor_gain	0.9900
19:8302557:C:CT	acceptor_gain	0.9900
19:8302601:CACCG:C	acceptor_gain	0.9900
19:8302602:ACCG:A	acceptor_gain	0.9900
19:8302603:CCGC:C	acceptor_gain	0.9900
19:8302604:CG:C	acceptor_gain	0.9900
19:8302768:C:A	donor_gain	0.9900
19:8302811:T:TA	donor_gain	0.9900
19:8302976:GGTTC:G	acceptor_gain	0.9900
19:8302977:GTTC:G	acceptor_gain	0.9900
19:8302978:TTC:T	acceptor_gain	0.9900
19:8302979:TC:T	acceptor_gain	0.9900
19:8302980:CC:C	acceptor_gain	0.9900

AlphaMissense

1789 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8305123:A:C	F59C	0.997
19:8303899:T:A	D153V	0.994
19:8305060:C:G	C80S	0.994
19:8305061:A:T	C80S	0.994
19:8305075:T:A	D75V	0.994
19:8305045:T:G	D85A	0.993
19:8305075:T:G	D75A	0.993
19:8303869:T:G	D163A	0.992
19:8305046:C:A	D85Y	0.992
19:8305117:C:G	C61S	0.992
19:8305118:A:T	C61S	0.992
19:8305122:G:C	F59L	0.992
19:8305122:G:T	F59L	0.992
19:8305124:A:G	F59L	0.992
19:8303899:T:G	D153A	0.991
19:8303907:C:A	W150C	0.991
19:8303907:C:G	W150C	0.991
19:8305045:T:A	D85V	0.991
19:8305046:C:G	D85H	0.991
19:8305060:C:T	C80Y	0.991
19:8305083:C:A	W72C	0.991
19:8305083:C:G	W72C	0.991
19:8303870:C:A	D163Y	0.990
19:8305059:G:C	C80W	0.990
19:8305078:C:G	C74S	0.990
19:8305079:A:T	C74S	0.990
19:8303869:T:A	D163V	0.989
19:8305045:T:C	D85G	0.989
19:8303869:T:C	D163G	0.988
19:8303870:C:G	D163H	0.987

dbSNP variants (sampled 300 via entrez): RS1000026642 (19:8309461 G>A), RS1001187668 (19:8304811 C>A), RS1001351074 (19:8302036 C>G), RS1001653389 (19:8301770 C>G,T), RS1001872183 (19:8308657 C>T), RS1002219073 (19:8306050 A>G), RS1002446194 (19:8301759 C>T), RS1002478212 (19:8309926 G>A,T), RS1002970130 (19:8307364 G>A), RS1003142067 (19:8307814 C>G,T), RS1003366693 (19:8304001 C>A,G,T), RS1003565306 (19:8308329 C>A,G,T), RS1003671157 (19:8303817 T>C), RS1003984487 (19:8303625 G>C), RS1004231504 (19:8308168 C>A,T)

Disease associations

OMIM: gene MIM:606475 | disease phenotypes: MIM:613646

GenCC curated gene-disease

Disease	Classification	Inheritance
methylmalonic acidemia due to transcobalamin receptor defect	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
methylmalonic acidemia due to transcobalamin receptor defect	Definitive	AR

Mondo (1): methylmalonic acidemia due to transcobalamin receptor defect (MONDO:0013341)

Orphanet (1): Methylmalonic aciduria due to transcobalamin receptor defect (Orphanet:280183)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002160	Hyperhomocystinemia
HP:0002912	Methylmalonic acidemia
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0012120	Methylmalonic aciduria
HP:0034985	Reduced cellular cobalamin uptake

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007208_11	Obsessive-compulsive disorder	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
bisphenol A	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiodarone	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	increases expression	1
Doxorubicin	increases expression, affects expression	1
Ethyl Methanesulfonate	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3Y7	WG3733	Finite cell line
CVCL_B3ZB	WG4131	Finite cell line	Male
CVCL_B4DA	WG3572	Finite cell line

Clinical trials (associated diseases)

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