CTBP1

C-terminal binding protein 1

Basic information

Region (hg38): 4:1211445-1250333

Links

ENSG00000159692 ∙ NCBI:1487 ∙ OMIM:602618 ∙ HGNC:2494 ∙ Uniprot:Q13363 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (Strong), mode of inheritance: AD
• hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (Strong), mode of inheritance: AD
• hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome	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	Dental; Neurologic	27094857

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTBP1 gene.

• not provided (1 variants)
• Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTBP1 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			2	90	5	97
missense	1		72	12	1	86
nonsense						0
start loss						0
frameshift				1		1
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)						0
splice region			8	16	2	26
non coding			2	26	6	34
Total	1	1	79	129	12

Variants in CTBP1

This is a list of pathogenic ClinVar variants found in the CTBP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-1212253-C-T			Uncertain significance (Aug 10, 2022)
4-1212256-G-T			Uncertain significance (Jul 01, 2022)
4-1212257-C-T			Likely benign (Sep 01, 2024)
4-1212258-G-A			Likely benign (Jul 13, 2022)
4-1212261-G-A			Likely benign (Mar 01, 2022)
4-1212270-C-T			Benign (Jul 29, 2023)
4-1212271-G-A			Uncertain significance (Oct 24, 2022)
4-1212273-C-T			Likely benign (Jun 01, 2024)
4-1212284-C-T		Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome	Uncertain significance (Nov 01, 2023)
4-1212298-G-A			Uncertain significance (Jun 23, 2024)
4-1212301-G-A			Conflicting classifications of pathogenicity (Oct 03, 2023)
4-1212305-C-A			Uncertain significance (May 24, 2024)
4-1212305-C-T		Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome	Uncertain significance (Dec 19, 2024)
4-1212306-G-A			Likely benign (Jan 01, 2023)
4-1212307-T-TG			Uncertain significance (Jul 08, 2024)
4-1212312-C-G			Likely benign (Nov 01, 2022)
4-1212312-C-T			Likely benign (Dec 11, 2022)
4-1212316-T-A			Benign/Likely benign (Sep 01, 2023)
4-1212319-G-A			Uncertain significance (Feb 13, 2023)
4-1212321-C-A			Likely benign (Aug 17, 2023)
4-1212323-C-T			Uncertain significance (May 15, 2024)
4-1212324-A-T		CTBP1-related disorder	Benign (Jan 29, 2024)
4-1212327-G-C			Likely benign (Jan 17, 2024)
4-1212335-C-T		Inborn genetic diseases • Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome	Uncertain significance (Mar 25, 2024)
4-1212336-G-A			Likely benign (Jun 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTBP1	protein_coding	protein_coding	ENST00000290921	9	38506

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.984	0.0156	125535	0	2	125537	0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.31	126	283	0.446	0.0000196	2799
Missense in Polyphen		15	80.278	0.18685		813
Synonymous	0.0174	133	133	0.998	0.0000107	916
Loss of Function	3.60	1	17.0	0.0587	8.99e-7	189

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Corepressor targeting diverse transcription regulators such as GLIS2 or BCL6. Has dehydrogenase activity. Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Functions in brown adipose tissue (BAT) differentiation. {ECO:0000269|PubMed:12419229, ECO:0000269|PubMed:15542832, ECO:0000269|PubMed:18212045, ECO:0000269|PubMed:19103759, ECO:0000269|PubMed:9858600}.
• Disease: DISEASE: Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (HADDTS) [MIM:617915]: An autosomal dominant disorder characterized by delayed motor development, intellectual disability, failure to thrive, hypotonia, ataxia, and tooth enamel defects. {ECO:0000269|PubMed:27094857}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Chronic myeloid leukemia - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);NOTCH-Ncore;Notch Signaling Pathway;Ectoderm Differentiation;Wnt Signaling Pathway;Pathways Affected in Adenoid Cystic Carcinoma;Wnt Signaling Pathway and Pluripotency;Notch Signaling Pathway;Wnt Signaling Pathway;Degradation of beta-catenin by the destruction complex;Signaling by WNT;Signal Transduction;wnt signaling pathway;Repression of WNT target genes;sumoylation as a mechanism to modulate ctbp-dependent gene responses;EGFR1;Notch signaling pathway;Wnt;Regulation of nuclear beta catenin signaling and target gene transcription;Notch-mediated HES/HEY network;Regulation of retinoblastoma protein;ATM pathway;Regulation of nuclear SMAD2/3 signaling;Presenilin action in Notch and Wnt signaling (Consensus)

Recessive Scores

• pRec: 0.387

Intolerance Scores

• loftool: 0.0645
• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Haploinsufficiency Scores

• pHI: 0.990
• hipred: Y
• hipred_score: 0.783
• ghis: 0.664

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ctbp1
• Phenotype: growth/size/body region 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); muscle 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); 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); embryo phenotype; skeleton phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;protein phosphorylation;negative regulation of cell population proliferation;viral genome replication;positive regulation of histone deacetylation;negative regulation of histone acetylation;negative regulation of transcription, DNA-templated;white fat cell differentiation;regulation of cell cycle;oxidation-reduction process;negative regulation of histone H4 acetylation
• Cellular component: nucleus;nucleoplasm;transcription factor complex;transcriptional repressor complex;presynaptic active zone cytoplasmic component;glutamatergic synapse;GABA-ergic synapse
• Molecular function: DNA-binding transcription factor activity;transcription corepressor activity;protein binding;protein C-terminus binding;transcription factor binding;oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor;protein domain specific binding;NAD binding;repressing transcription factor binding