CBX2

chromobox 2, the group of Chromobox family

Basic information

Region (hg38): 17:79778147-79787983

Previous symbols: [ "CDCA6" ]

Links

ENSG00000173894 ∙ NCBI:84733 ∙ OMIM:602770 ∙ HGNC:1552 ∙ Uniprot:Q14781 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46,XY sex reversal 5 (Limited), mode of inheritance: Semidominant
• 46,XY complete gonadal dysgenesis (Supportive), mode of inheritance: AD
• 46,XY sex reversal 5 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
46,XY sex reversal 5	AR	General	There was no evidence for dysgenetic gonads in the reported patient; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine; Genitourinary	19361780

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CBX2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CBX2 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				23	9	32
missense			61	9	3	73
nonsense						0
start loss						0
frameshift			1	1		2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			1	2	2	5
Total	0	0	63	35	14

Variants in CBX2

This is a list of pathogenic ClinVar variants found in the CBX2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-79778245-C-G			Uncertain significance (Sep 16, 2021)
17-79778283-C-T			Likely benign (Feb 22, 2023)
17-79778304-C-A			Benign/Likely benign (Jul 21, 2023)
17-79778326-GC-G			Benign (Sep 03, 2021)
17-79778365-C-G			Likely benign (Jan 21, 2023)
17-79778377-C-A			Uncertain significance (Jun 03, 2021)
17-79778393-G-C		not specified	Uncertain significance (Jul 11, 2022)
17-79779341-GC-G		46,XY sex reversal 5	Uncertain significance (Mar 26, 2024)
17-79779348-C-T			Likely benign (Oct 21, 2021)
17-79779359-C-T		Disorder of sexual differentiation	Uncertain significance (Feb 01, 2021)
17-79779392-C-T			Benign (Jan 29, 2024)
17-79779446-C-CTG			Benign (Jan 29, 2024)
17-79781721-C-T		not specified	Uncertain significance (May 03, 2023)
17-79781730-G-C		not specified	Uncertain significance (Mar 14, 2023)
17-79781748-C-T		not specified	Uncertain significance (Dec 22, 2023)
17-79781769-A-G		not specified	Uncertain significance (Apr 26, 2024)
17-79781775-TC-T		46,XY sex reversal 5	Uncertain significance (Nov 17, 2016)
17-79781780-C-T		CBX2-related disorder	Likely benign (Apr 03, 2019)
17-79781784-C-T		not specified	Uncertain significance (Apr 25, 2022)
17-79781844-C-T			Likely benign (Sep 01, 2022)
17-79781853-G-T		CBX2-related disorder	Uncertain significance (Sep 06, 2023)
17-79781948-T-G			Likely benign (Nov 01, 2022)
17-79781972-CT-C			Likely benign (Apr 01, 2023)
17-79783735-C-G		not specified	Uncertain significance (Mar 14, 2023)
17-79783736-C-T		46,XY sex reversal 5	Pathogenic (May 01, 2009)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CBX2	protein_coding	protein_coding	ENST00000310942	5	9852

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00497	123467	0	4	123471	0.0000162

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.262	345	332	1.04	0.0000209	3407
Missense in Polyphen		95	104.49	0.90916		1133
Synonymous	-2.98	196	150	1.31	0.0000103	1135
Loss of Function	3.67	0	15.7	0.00	8.58e-7	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000584	0.0000584
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000197	0.0000181
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1- like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:21282530). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:21282530). Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3) or at 'Lys-27' (H3K27me3) (By similarity). Plays a role in the lineage differentiation of the germ layers in embryonic development (By similarity). Involved in sexual development, acting as activator of NR5A1 expression (PubMed:19361780). {ECO:0000250|UniProtKB:P30658, ECO:0000269|PubMed:19361780, ECO:0000269|PubMed:21282530}.
• Disease: DISEASE: 46,XY sex reversal 5 (SRXY5) [MIM:613080]: A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. {ECO:0000269|PubMed:19361780}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;Oxidative Stress Induced Senescence;SUMOylation of DNA damage response and repair proteins;Cellular Senescence;SUMOylation of chromatin organization proteins;Cellular responses to stress;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;SUMOylation;Cellular responses to external stimuli;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Intracellular signaling by second messengers;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.0658
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.07

Haploinsufficiency Scores

• pHI: 0.133
• hipred: Y
• hipred_score: 0.809
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.955

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cbx2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system 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); reproductive system phenotype; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin organization;cell differentiation;development of primary sexual characteristics
• Cellular component: euchromatin;heterochromatin;nucleus;nucleoplasm;PcG protein complex;PRC1 complex
• Molecular function: DNA binding;chromatin binding;protein binding;methylated histone binding