CEBPE

protein-coding

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

Gene summary

The protein encoded by this gene is a bZIP transcription factor which can bind as a homodimer to certain DNA regulatory regions. It can also form heterodimers with the related protein CEBP-delta. The encoded protein may be essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells. Mutations in this gene have been associated with Specific Granule Deficiency, a rare congenital disorder. Multiple variants of this gene have been described, but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001805.4

Inheritance

ClinVar variants

P:11U:122B:97

Top phenotype

Specific granule deficiency 1; Immunodeficiency 108 with autoinflammation

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr14:23,117,036-23,120,256

External References & Databases

Ensembl (ENSG00000092067)

Transcript & Mutation Effects

hg38 • Region Span ~3.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

specific granule deficiency 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044207

Submitter: Labcorp Genetics (formerly Invitae)

specific granule deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009506

Submitter: Orphanet

Clinical Genomic Database (CGD)

Specific granule deficiency 1; Immunodeficiency 108 with autoinflammationAR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals with Specific granule deficiency have severe immunocompromise, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Immunodeficiency108 with autoinflammation involves immunodeficiency, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficia

Refs: 10359588; 11313242; 31201888

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CEBPE variants in ClinVar

8 Conditions Cataloged

Specific granule deficiencyTotal: 206

Inborn genetic diseasesTotal: 44

not providedTotal: 30

not specifiedTotal: 25

CEBPE-related disorderTotal: 18

Specific granule deficiency 1Total: 9

SPECIFIC GRANULE DEFICIENCY 1, AUTOSOMAL DOMINANTTotal: 1

Pelger-Huet-like anomaly and episodic fever with abdominal painTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001805.4. 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	91 clinvar	1 clinvar	93
missense		2 clinvar	118 clinvar	4 clinvar	1 clinvar	125
nonsense	2 clinvar	2 clinvar	2 clinvar			6
start loss						0
frameshift	5 clinvar		1 clinvar			6
splice donor/acceptor (+/-2bp)						0
Total	7	4	122	95	2	230

Highest pathogenic variant AF is 0.0000082136985

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001805.4	RefSeq	NP_001796.2	2	MANE Select
ENST00000206513.6	Ensembl	ENSP00000206513.5	2	MANE Select
ENST00001136249.1	Ensembl	ENSP00000801431.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Acute myeloid leukemia - Homo sapiens (human)
Transcriptional misregulation in cancer - Homo sapiens (human)

Biological Process

phagocytosis
defense response
macrophage differentiation
granulocyte differentiation
cytokine biosynthetic process

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
protein binding
protein homodimerization activity

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000206513
Coding exons: 2
Length: 2313
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125742
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.233	180	189	0.952	0.0000131	1788
Missense (PolyPhen)		84	87.333	0.96184		858
Synonymous	-0.705	90	81.9	1.10	0.00000577	609
Loss of Function	1.59	5	10.6	0.473	8.07e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000073	0.000070	rare
South Asian	0.000099	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional activator (PubMed:26019275). C/EBP are DNA-binding proteins that recognize two different motifs: the CCAAT homology common to many promoters and the enhanced core homology common to many enhancers. Required for the promyelocyte- myelocyte transition in myeloid differentiation (PubMed:10359588). {ECO:0000269|PubMed:10359588, ECO:0000269|PubMed:26019275}.;
Disease: DISEASE: Specific granule deficiency 1 (SGD1) [MIM:245480]: An autosomal recessive disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. Neutrophils of affected individuals lack lactoferrin and show abnormal nuclear segmentation, bilobed nuclei, low alkaline phosphatase, and increased number of neutrophil mitochondria and ribosomes. {ECO:0000269|PubMed:10359588, ECO:0000269|PubMed:11313242, ECO:0000269|PubMed:26019275}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.213

Intolerance Scores

LoFtool: 0.507
RVIS EVS: -0.38
RVIS percentile EVS: 27.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.944

Gene Damage Prediction

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