CREBL2

protein-coding

cAMP responsive element binding protein like 2, the group of Basic leucine zipper proteins

Gene summary

cAMP response element (CRE)-binding protein-like-2 (CREBL2) was identified in a search to find genes in a commonly deleted region on chromosome 12p13 flanked by ETV6 and CDKN1B genes, frequently associated with hematopoietic malignancies, as well as breast, non-small-cell lung and ovarian cancers. CREBL2 shares a 41% identity with CRE-binding protein (CREB) over a 48-base long region which encodes the bZip domain of CREB. The bZip domain consists of about 30 amino acids rich in basic residues involved in DNA binding, followed by a leucine zipper motif involved in protein dimerization. This suggests that CREBL2 encodes a protein with DNA binding capabilities. The occurance of CREBL2 deletion in malignancy suggests that CREBL2 may act as a tumor suppressor gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001310.4

Inheritance

—

ClinVar variants

P:1U:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr12:12,611,827-12,645,108

External References & Databases

Ensembl (ENSG00000111269)

Transcript & Mutation Effects

hg38 • Region Span ~33.3 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 CREBL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 10

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001310.4. 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						0
missense			11 clinvar			11
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	1	15	0	0	16

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001310.4	RefSeq	NP_001301.1	4	MANE Select
ENST00000228865.3	Ensembl	ENSP00000228865.2	4	MANE Select
ENST00000893303.1	Ensembl	ENSP00000563362.1	3	Standard
ENST00000893303.2	Ensembl	ENSP00000563362.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

transcription, DNA-templated
regulation of transcription by RNA polymerase II
cell cycle
signal transduction
cell differentiation

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000228865
Coding exons: 4
Length: 33282
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125728
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.50	32	66.3	0.483	0.00000364	783
Missense (PolyPhen)		6	26.123	0.22968		323
Synonymous	0.817	16	20.7	0.772	9.78e-7	212
Loss of Function	2.39	1	8.53	0.117	6.11e-7	93

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000090	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable regulator of CREB1 transcriptional activity which is involved in adipose cells differentiation. May also play a regulatory role in the cell cycle. Identification in a chromosomal region frequently deleted in various cancers suggests that it might act as a tumor suppressor. {ECO:0000269|PubMed:9693048}.;

Recessive Scores

pRec: 0.137

Intolerance Scores

RVIS EVS: 0.1
RVIS percentile EVS: 60.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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