CD320

CD320 molecule, the group of CD molecules

Basic information

Region (hg38): 19:8302126-8308358

Links

ENSG00000167775 ∙ NCBI:51293 ∙ OMIM:606475 ∙ HGNC:16692 ∙ Uniprot:Q9NPF0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• methylmalonic acidemia due to transcobalamin receptor defect (Limited), mode of inheritance: AR
• methylmalonic acidemia due to transcobalamin receptor defect (Supportive), mode of inheritance: AR
• methylmalonic acidemia due to transcobalamin receptor defect (Limited), mode of inheritance: Unknown
• methylmalonic acidemia due to transcobalamin receptor defect (Limited), mode of inheritance: Unknown
• methylmalonic acidemia due to transcobalamin receptor defect (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Methylmalonic aciduria, transient, due to transcobalamin receptor defect	AR	Biochemical; Ophthalmologic	Medical treatment (eg, with IV B6 and IM B12-hydroxocobalamine) has been shown to positively affect laboratory parameters, and may be clinically beneficial though long-term clinical sequelae are unclear	Biochemical; Ophthalmologic	20524213; 22819238

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CD320 gene.

• Methylmalonic acidemia due to transcobalamin receptor defect (103 variants)
• not provided (38 variants)
• Inborn genetic diseases (15 variants)
• not specified (14 variants)
• CD320-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CD320 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	26	6	33
missense			49	6	4	59
nonsense			2			2
start loss						0
frameshift			1			1
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding				10	33	43
Total	0	0	56	42	43

Variants in CD320

This is a list of pathogenic ClinVar variants found in the CD320 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-8302274-C-T			Benign (Jul 31, 2018)
19-8302334-G-A			Benign (Nov 16, 2018)
19-8302380-G-C			Benign (May 25, 2021)
19-8302472-C-T		Methylmalonic acidemia due to transcobalamin receptor defect	Benign/Likely benign (Sep 07, 2022)
19-8302473-G-A		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Aug 19, 2022)
19-8302475-G-C		not specified • Methylmalonic acidemia due to transcobalamin receptor defect	Benign (Jan 28, 2024)
19-8302512-G-A		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Dec 25, 2023)
19-8302523-C-T		CD320-related disorder	Likely benign (Jun 27, 2019)
19-8302533-C-T		not specified	Uncertain significance (Jan 23, 2024)
19-8302539-C-T		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Jul 10, 2023)
19-8302540-G-A		not specified • Methylmalonic acidemia due to transcobalamin receptor defect	Benign (Dec 22, 2023)
19-8302543-C-T		Methylmalonic acidemia due to transcobalamin receptor defect	Benign/Likely benign (Jan 26, 2024)
19-8302551-C-T		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Sep 13, 2022)
19-8302552-G-A		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Jul 12, 2022)
19-8302552-G-T		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Feb 22, 2022)
19-8302553-G-A		not specified • Methylmalonic acidemia due to transcobalamin receptor defect	Benign/Likely benign (Sep 23, 2023)
19-8302567-G-A		Methylmalonic acidemia due to transcobalamin receptor defect • CD320-related disorder	Likely benign (Nov 07, 2023)
19-8302581-G-A		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Oct 13, 2023)
19-8302590-C-T		Methylmalonic acidemia due to transcobalamin receptor defect	Likely benign (Jul 07, 2023)
19-8302604-C-A		Methylmalonic acidemia due to transcobalamin receptor defect	Likely benign (Feb 03, 2022)
19-8302604-C-T		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Feb 24, 2020)
19-8302605-G-A		not specified	Likely benign (Apr 25, 2023)
19-8302620-T-A		not specified • Methylmalonic acidemia due to transcobalamin receptor defect	Benign (Feb 01, 2024)
19-8302641-G-C			Benign (Aug 10, 2018)
19-8302798-A-G		Methylmalonic acidemia due to transcobalamin receptor defect	Uncertain significance (Oct 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CD320	protein_coding	protein_coding	ENST00000301458	5	6230

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00352	0.851	125668	0	19	125687	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.244	160	169	0.947	0.0000101	1730
Missense in Polyphen		34	46.037	0.73854		493
Synonymous	-0.528	82	76.1	1.08	0.00000511	610
Loss of Function	1.22	5	8.93	0.560	3.81e-7	101

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000600	0.000598
Finnish	0.0000495	0.0000462
European (Non-Finnish)	0.0000367	0.0000352
Middle Eastern	0.000600	0.000598
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for transcobalamin saturated with cobalamin (TCbl) (PubMed:18779389). Plays an important role in cobalamin uptake (PubMed:18779389, PubMed:20524213). Plasma membrane protein that is expressed on follicular dendritic cells (FDC) and mediates interaction with germinal center B cells (PubMed:10727470). Functions as costimulator to promote B cell responses to antigenic stimuli; promotes B cell differentiation and proliferation (PubMed:10727470, PubMed:11418631). 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) (PubMed:11418631). CD320 augments the proliferation of PC precursors generated by IL-10 (PubMed:11418631). {ECO:0000269|PubMed:10727470, ECO:0000269|PubMed:11418631, ECO:0000269|PubMed:18779389, ECO:0000269|PubMed:20524213}.
• Pathway: Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.191

Intolerance Scores

• loftool: 0.125
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.0540
• hipred: N
• hipred_score: 0.146
• ghis: 0.392

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.614

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cd320
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; immune system phenotype; vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cobalamin metabolic process;regulation of signaling receptor activity;cobalamin transport;regulation of vitamin metabolic process;positive regulation of B cell proliferation;B cell costimulation
• Cellular component: endoplasmic reticulum;plasma membrane;integral component of plasma membrane;endosome membrane;membrane
• Molecular function: calcium ion binding;protein binding;growth factor activity;cobalamin-transporting ATPase activity;cobalamin binding