CEBPB

protein-coding

CCAAT enhancer binding protein beta, the group of CCAAT/enhancer binding proteins |Basic leucine zipper proteins

Gene summary

This intronless gene encodes a transcription factor that contains a basic leucine zipper (bZIP) domain. The encoded protein functions as a homodimer but can also form heterodimers with CCAAT/enhancer-binding proteins alpha, delta, and gamma. Activity of this protein is important in the regulation of genes involved in immune and inflammatory responses, among other processes. The use of alternative in-frame AUG start codons results in multiple protein isoforms, each with distinct biological functions. [provided by RefSeq, Oct 2013]

Previous symbols:

TCF5

MANE transcript

NM_005194.4

Inheritance

—

ClinVar variants

U:48B:2

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr20:50,190,734-50,192,690

External References & Databases

Ensembl (ENSG00000172216)

Transcript & Mutation Effects

hg38 • Region Span ~2.0 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 CEBPB variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 49

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005194.4. 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				1 clinvar		1
missense			48 clinvar	1 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	48	2	0	50

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005194.4	RefSeq	NP_005185.2	1	MANE Select
ENST00000303004.5	Ensembl	ENSP00000305422.3	1	MANE Select
NM_001285878.1	RefSeq	NP_001272807.1	1	Standard
NM_001285879.1	RefSeq	NP_001272808.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TNF signaling pathway - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)
IL-17 signaling pathway - Homo sapiens (human)
Transcriptional misregulation in cancer - Homo sapiens (human)
Folate-Alcohol and Cancer Pathway Hypotheses

Biological Process

negative regulation of transcription by RNA polymerase II
ovarian follicle development
embryonic placenta development
regulation of transcription, DNA-templated
transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
RNA polymerase II core promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific

Cellular Component

condensed chromosome, centromeric region
nuclear chromatin
nucleus
nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000303004
Coding exons: 1
Length: 1837
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.897	92	120	0.769	0.00000557	2122
Missense (PolyPhen)		17	39.395	0.43152		599
Synonymous	-1.76	74	57.1	1.30	0.00000291	728
Loss of Function	1.56	1	4.61	0.217	1.96e-7	86

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
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	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Important transcription factor regulating the expression of genes involved in immune and inflammatory responses (PubMed:1741402, PubMed:9374525, PubMed:12048245, PubMed:18647749). Plays also a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'- T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant functions with CEBPA. Has a promitotic effect on many cell types such as hepatocytes and adipocytes but has an antiproliferative effect on T-cells by repressing MYC expression, facilitating differentiation along the T-helper 2 lineage. Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Plays also a role in intracellular bacteria killing (By similarity). During adipogenesis, is rapidly expressed and, after activation by phosphorylation, induces CEBPA and PPARG, which turn on the series of adipocyte genes that give rise to the adipocyte phenotype. The delayed transactivation of the CEBPA and PPARG genes by CEBPB appears necessary to allow mitotic clonal expansion and thereby progression of terminal differentiation (PubMed:20829347). Essential for female reproduction because of a critical role in ovarian follicle development (By similarity). Restricts osteoclastogenesis: together with NFE2L1; represses expression of DSPP during odontoblast differentiation (By similarity). {ECO:0000250|UniProtKB:P21272, ECO:0000250|UniProtKB:P28033, ECO:0000269|PubMed:12048245, ECO:0000269|PubMed:18647749, ECO:0000269|PubMed:20829347, ECO:0000269|PubMed:9374525, ECO:0000303|PubMed:25451943}.; FUNCTION: Isoform 3: Acts as a dominant negative through heterodimerization with isoform 2 (PubMed:11741938). Promotes osteoblast differentiation and osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:P21272, ECO:0000250|UniProtKB:P28033, ECO:0000269|PubMed:11741938}.;

Recessive Scores

pRec: 0.107

Essentials

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

Gene Damage Prediction

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