MYCBP2

MYC binding protein 2, the group of Ring finger proteins

Basic information

Region (hg38): 13:77042474-77327094

Links

ENSG00000005810 ∙ NCBI:23077 ∙ OMIM:610392 ∙ HGNC:23386 ∙ Uniprot:O75592 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYCBP2 gene.

• Inborn_genetic_diseases (387 variants)
• not_provided (245 variants)
• MYCBP2-related_disorder (68 variants)
• MYCBP2-related_developmental_delay_with_corpus_callosum_defects (2 variants)
• not_specified (2 variants)
• See_cases (2 variants)
• Prostate_cancer (1 variants)
• MYCBP2-associated_neurodevelopmental_disorder (1 variants)
• Autism_spectrum_disorder_due_to_AUTS2_deficiency (1 variants)
• Global_developmental_delay (1 variants)
• MYCBP2-associated_disorder (1 variants)
• MYCBP2-related_neurodevelopmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYCBP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015057.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	1	36	9	47
missense	2	1	555	11	6	575
nonsense	5	2	10			17
start loss			1	1		2
frameshift	1	1	8			10
splice donor/acceptor (+/-2bp)		2	6			8
Total	8	7	581	48	15

Highest pathogenic variant AF is 0.00000188085

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYCBP2	protein_coding	protein_coding	ENST00000544440	83	282394

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.11e-25	125710	0	38	125748	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	6.05	1566	2.40e+3	0.653	0.000122	30359
Missense in Polyphen		702	1343.9	0.52237		17269
Synonymous	0.0144	848	849	0.999	0.0000443	8938
Loss of Function	13.0	18	233	0.0773	0.0000130	2916

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000149
Ashkenazi Jewish	0.000498	0.000496
East Asian	0.0000544	0.0000544
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000151	0.000149
Middle Eastern	0.0000544	0.0000544
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (PubMed:29643511). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (PubMed:29643511). Interacts with the E2 enzymes UBE2D1, UBE2D3, UBE2E1 and UBE2L3 (PubMed:18308511, PubMed:29643511). Plays a key role in neural development, probably by mediating ubiquitination of threonine residues on target proteins (Probable). Involved in different processes such as regulation of neurite outgrowth, synaptic growth, synaptogenesis and axon degeneration (By similarity). Required for the formation of major central nervous system axon tracts (By similarity). Required for proper axon growth by regulating axon navigation and axon branching: acts by regulating the subcellular location and stability of MAP3K12/DLK (By similarity). Required for proper localization of retinogeniculate projections but not for eye-specific segregation (By similarity). Regulates axon guidance in the olfactory system (By similarity). Involved in Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons: acts by promoting destabilization of NMNAT2, probably via ubiquitination of NMNAT2 (By similarity). Catalyzes ubiquitination of threonine and/or serine residues on NMNAT2, consequences of threonine and/or serine ubiquitination are however unknown (PubMed:29643511). Regulates the internalization of TRPV1 in peripheral sensory neurons (By similarity). May mediate ubiquitination and subsequent proteasomal degradation of TSC2/tuberin (PubMed:18308511). Independently of the E3 ubiquitin-protein ligase activity, also acts as a guanosine exchange factor (GEF) for RAN in neurons of dorsal root ganglia (PubMed:26304119). May function as a facilitator or regulator of transcriptional activation by MYC (PubMed:9689053). {ECO:0000250|UniProtKB:Q7TPH6, ECO:0000269|PubMed:18308511, ECO:0000269|PubMed:26304119, ECO:0000269|PubMed:29643511, ECO:0000269|PubMed:9689053}.
• Pathway: Integrated Breast Cancer Pathway (Consensus)

Recessive Scores

• pRec: 0.110

Haploinsufficiency Scores

• pHI: 0.519
• hipred: Y
• hipred_score: 0.652
• ghis: 0.615

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.930

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mycbp2
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: mycbp2
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: displaced

Gene ontology

• Biological process: protein ubiquitination;branchiomotor neuron axon guidance;central nervous system projection neuron axonogenesis;regulation of protein localization;negative regulation of protein catabolic process;neuromuscular process;regulation of cytoskeleton organization;regulation of axon guidance
• Cellular component: nucleus;cytoplasm;microtubule cytoskeleton;membrane;axon;intracellular membrane-bounded organelle
• Molecular function: guanyl-nucleotide exchange factor activity;protein binding;zinc ion binding;Ran GTPase binding;protein homodimerization activity;ubiquitin protein ligase activity