CEBPA

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

Basic information

Region (hg38): 19:33299934-33302534

Previous symbols: [ "CEBP" ]

Links

ENSG00000245848 ∙ NCBI:1050 ∙ OMIM:116897 ∙ HGNC:1833 ∙ Uniprot:P49715 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acute myeloid leukemia (Strong), mode of inheritance: AD
• acute myeloid leukemia (Moderate), mode of inheritance: AD
• acute myeloid leukemia (Definitive), mode of inheritance: AD
• acute myeloid leukemia (Strong), mode of inheritance: AD
• acute myeloid leukemia (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acute myeloid leukemia, familial	AD	Oncologic	Surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of malignancy, which may reduce morbidity and mortality	Oncologic	15575056; 15902292; 18768433; 18946494; 20963938; 22066712; 23716546

ClinVar

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

• Acute_myeloid_leukemia (957 variants)
• Inborn_genetic_diseases (588 variants)
• not_provided (121 variants)
• Hereditary_cancer-predisposing_syndrome (37 variants)
• CEBPA-related_disorder (35 variants)
• not_specified (30 variants)
• Autosomal_dominant_familial_acute_myeloid_leukemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEBPA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004364.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	23	349	2	375
missense	4	7	565	90	1	667
nonsense	8	2	10			20
start loss						0
frameshift	25	10	17			52
splice donor/acceptor (+/-2bp)						0
Total	37	20	615	439	3

Highest pathogenic variant AF is 0.0000541635

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEBPA	protein_coding	protein_coding	ENST00000498907	1	2631

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.554	0.399	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.568	72	86.9	0.828	0.00000405	2254
Missense in Polyphen		25	45.924	0.54438		816
Synonymous	-0.0910	41	40.3	1.02	0.00000194	775
Loss of Function	1.44	0	2.43	0.00	1.03e-7	73

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta. Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes (PubMed:11242107). During early embryogenesis, plays essential and redundant functions with CEBPB. Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP). Critical for the proper development of the liver and the lung (By similarity). Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (By similarity). To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Downregulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters. Proliferation arrest also depends on a functional binding to SWI/SNF complex (PubMed:14660596). In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC. To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2. In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (By similarity). {ECO:0000250|UniProtKB:P05554, ECO:0000250|UniProtKB:P53566, ECO:0000269|PubMed:11242107, ECO:0000269|PubMed:14660596}.; FUNCTION: Isoform 4: Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation. {ECO:0000269|PubMed:20075868}.
• Disease: DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:11242107, ECO:0000269|PubMed:12661007, ECO:0000269|PubMed:15575056}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Transcriptional regulation of white adipocyte differentiation;White fat cell differentiation;Adipogenesis;Vitamin D Receptor Pathway;Differentiation of white and brown adipocyte;Transcription factor regulation in adipogenesis;Pathways Affected in Adenoid Cystic Carcinoma;IL-4 Signaling Pathway;White fat cell differentiation;Transcriptional cascade regulating adipogenesis;keratinocyte differentiation;mapkinase signaling pathway;AndrogenReceptor;EGFR1;C-MYB transcription factor network;IL4;Validated targets of C-MYC transcriptional repression;Regulation of Androgen receptor activity;Regulation of retinoblastoma protein;FOXA2 and FOXA3 transcription factor networks;E2F transcription factor network (Consensus)

Recessive Scores

• pRec: 0.107

Haploinsufficiency Scores

• ghis: 0.575

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cebpa
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; neoplasm; reproductive system 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); normal phenotype; 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); hematopoietic system phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: cebpa
• Affected structure: myeloid lineage restricted progenitor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: urea cycle;negative regulation of transcription by RNA polymerase II;liver development;embryonic placenta development;generation of precursor metabolites and energy;transcription, DNA-templated;transcription by RNA polymerase II;mitochondrion organization;Notch signaling pathway;cholesterol metabolic process;negative regulation of cell population proliferation;viral process;cytokine-mediated signaling pathway;myeloid cell differentiation;macrophage differentiation;lung development;granulocyte differentiation;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;glucose homeostasis;positive regulation of macrophage activation;fat cell differentiation;positive regulation of fat cell differentiation;positive regulation of osteoblast differentiation;negative regulation of cyclin-dependent protein serine/threonine kinase activity;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of transcription by RNA polymerase III;cell maturation;inner ear development;positive regulation of inflammatory response;white fat cell differentiation;brown fat cell differentiation;lipid homeostasis;cellular response to lithium ion;cellular response to tumor necrosis factor;cellular response to organic cyclic compound
• Cellular component: nucleus;nucleoplasm;nucleolus;intracellular membrane-bounded organelle;RNA polymerase II transcription factor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;transcription factor binding;kinase binding;protein homodimerization activity;transcription regulatory region DNA binding