CUX2

cut like homeobox 2, the group of MicroRNA protein coding host genes|CUT class homeoboxes and pseudogenes

Basic information

Region (hg38): 12:111034164-111350554

Previous symbols: [ "CUTL2" ]

Links

ENSG00000111249 ∙ NCBI:23316 ∙ OMIM:610648 ∙ HGNC:19347 ∙ Uniprot:O14529 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 67 (Moderate), mode of inheritance: AD
• developmental and epileptic encephalopathy, 67 (Strong), mode of inheritance: AD
• Lennox-Gastaut syndrome (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 67	AD	General	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	Neurologic	29630738; 29795476

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CUX2 gene.

• not provided (115 variants)
• Inborn genetic diseases (52 variants)
• Developmental and epileptic encephalopathy, 67 (49 variants)
• CUX2-related condition (4 variants)
• not specified (4 variants)
• Intellectual disability (3 variants)
• See cases (2 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CUX2 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				31	5	36
missense		1	110	30	5	146
nonsense			2			2
start loss						0
frameshift		1	4			5
inframe indel				1	1	2
splice donor/acceptor (+/-2bp)			4			4
splice region			3	2	3	8
non coding			4	1		5
Total	0	2	124	63	11

Variants in CUX2

This is a list of pathogenic ClinVar variants found in the CUX2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-111034174-C-T			Uncertain significance (Nov 29, 2022)
12-111034188-A-G			Uncertain significance (Jun 12, 2023)
12-111034194-G-T			Uncertain significance (Jul 01, 2022)
12-111034249-G-C		CUX2-related disorder	Likely benign (Sep 18, 2019)
12-111214190-A-T			Likely benign (Aug 04, 2017)
12-111214214-C-T		CUX2-related disorder	Likely benign (Apr 01, 2022)
12-111214215-G-A		Inborn genetic diseases	Uncertain significance (Apr 29, 2021)
12-111214215-G-T		Developmental and epileptic encephalopathy, 67	Conflicting classifications of pathogenicity (May 01, 2023)
12-111214217-C-T		Developmental and epileptic encephalopathy, 67	Benign/Likely benign (Feb 01, 2024)
12-111214218-G-T		Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
12-111214273-T-C		Developmental and epileptic encephalopathy, 67	Uncertain significance (Apr 16, 2021)
12-111214281-C-T		Inborn genetic diseases	Likely benign (May 28, 2023)
12-111214303-T-C		Developmental and epileptic encephalopathy, 67	Uncertain significance (-)
12-111217908-G-C			Uncertain significance (Nov 01, 2023)
12-111217920-A-C			Uncertain significance (Nov 17, 2021)
12-111217935-G-A		Developmental and epileptic encephalopathy, 67	Uncertain significance (Nov 02, 2023)
12-111263760-G-A		Developmental and epileptic encephalopathy, 67	Uncertain significance (Oct 19, 2020)
12-111263776-A-G		Inborn genetic diseases	Uncertain significance (Mar 02, 2023)
12-111263792-C-T			Likely benign (Jan 01, 2024)
12-111263849-G-A		CUX2-related disorder	Likely benign (Apr 11, 2019)
12-111291422-C-T		CUX2-related disorder	Benign (May 24, 2019)
12-111291439-C-T			Likely benign (Oct 01, 2023)
12-111291470-C-T			Likely benign (Nov 01, 2023)
12-111291474-A-C		Developmental and epileptic encephalopathy, 67	Uncertain significance (Jan 30, 2020)
12-111291498-C-T		Intellectual disability	Likely benign (Jan 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CUX2	protein_coding	protein_coding	ENST00000261726	22	316531

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000193	124785	0	9	124794	0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.18	615	881	0.698	0.0000575	9418
Missense in Polyphen		161	324.11	0.49675		3372
Synonymous	1.62	365	407	0.898	0.0000292	3110
Loss of Function	6.67	6	63.2	0.0949	0.00000305	753

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000201	0.000129
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000479	0.0000464
European (Non-Finnish)	0.0000461	0.0000441
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be a transcription factor involved in neural specification. Binds to DNA in a sequence-specific manner (By similarity). {ECO:0000250}.

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.280
• rvis_EVS: -2.08
• rvis_percentile_EVS: 1.6

Haploinsufficiency Scores

• pHI: 0.247
• hipred: Y
• hipred_score: 0.711
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.227

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cux2
• Phenotype: embryo 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); 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); cellular phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;short-term memory;positive regulation of gene expression;Golgi vesicle transport;positive regulation of dendrite morphogenesis;cognition;positive regulation of synapse assembly;positive regulation of dendritic spine morphogenesis;cellular response to organic substance;positive regulation of excitatory postsynaptic potential
• Cellular component: Golgi membrane;nucleus;extracellular exosome
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;sequence-specific DNA binding