CTBP2

protein-coding

C-terminal binding protein 2, the group of MicroRNA protein coding host genes

Gene summary

This gene produces alternative transcripts encoding two distinct proteins. One protein is a transcriptional repressor, while the other isoform is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3' untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

MANE transcript

NM_001329.4

Inheritance

—

ClinVar variants

P:3U:4B:13

Top phenotype

CTBP2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr10:124,984,317-125,161,170

External References & Databases

Ensembl (ENSG00000175029)

Transcript & Mutation Effects

hg38 • Region Span ~176.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CTBP2 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 27

CTBP2-related disorderTotal: 27

Pulmonary artery atresiaTotal: 4

EBV-positive nodal T- and NK-cell lymphomaTotal: 2

not specifiedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001329.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				10 clinvar	1 clinvar	11
missense	3 clinvar		2 clinvar			5
nonsense				1 clinvar	1 clinvar	2
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	3	0	4	11	2	20

Highest pathogenic variant AF is 0.000019208033

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 280 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001329.4	RefSeq	NP_001320.1	9	MANE Select
ENST00000337195.11	Ensembl	ENSP00000338615.5	9	MANE Select
NM_001083914.3	RefSeq	NP_001077383.1	9	Standard
NM_001290214.3	RefSeq	NP_001277143.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ctbp2a	Danio rerio	Structure: rod bipolar cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

ctbp2a

Danio rerio

Structure: rod bipolar cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Chronic myeloid leukemia - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)
Wnt signaling pathway - Homo sapiens (human)
Notch signaling pathway - Homo sapiens (human)
Neural Crest Differentiation

Biological Process

negative regulation of cell population proliferation
synaptic vesicle docking
viral genome replication
positive regulation of chromatin binding
negative regulation of transcription, DNA-templated

Molecular Function

chromatin binding
transcription coactivator activity
transcription corepressor activity
protein binding
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor

Cellular Component

nucleus
transcriptional repressor complex
cell junction
photoreceptor ribbon synapse
presynaptic active zone cytoplasmic component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309035
Coding exons: 9
Length: 173319
Individuals with no LoFs: 125199
Homozygous LoFs: 1
Heterozygous LoFs: 546
Defined: 125746
p: 0.00218

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.06	581	657	0.884	0.0000442	6240
Missense (PolyPhen)		166	214.84	0.77267		2087
Synonymous	-1.07	314	291	1.08	0.0000212	2180
Loss of Function	3.79	12	36.8	0.326	0.00000208	366

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.0012	0.0012	notable
Ashkenazi Jewish	0.0040	0.0039	notable
East Asian	0.0013	0.0013	notable
Finnish	0.0010	0.0010	notable
European (Non-Finnish)	0.0035	0.0034	notable
South Asian	0.00046	0.00046	rare
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Corepressor targeting diverse transcription regulators. Functions in brown adipose tissue (BAT) differentiation (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.161

Intolerance Scores

LoFtool: 0.0302
RVIS EVS: 0.37
RVIS percentile EVS: 74.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High