CEBPD

Summary

CEBPD (CCAAT enhancer binding protein delta, HGNC:1835) is a protein-coding gene on chromosome 8q11.21, encoding CCAAT/enhancer-binding protein delta (P49716). Transcription activator that recognizes two different DNA motifs: the CCAAT homology common to many promoters and the enhanced core homology common to many enhancers.

The protein encoded by this intronless 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-alpha. The encoded protein is important in the regulation of genes involved in immune and inflammatory responses, and may be involved in the regulation of genes associated with activation and/or differentiation of macrophages. The cytogenetic location of this locus has been reported as both 8p11 and 8q11.

Source: NCBI Gene 1052 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 68 total
• Transcription factor: yes — 107 downstream targets (CollecTRI)
• MANE Select transcript: NM_005195

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1835
Approved symbol	CEBPD
Name	CCAAT enhancer binding protein delta
Location	8q11.21
Locus type	gene with protein product
Status	Approved
Aliases	CRP3, CELF, C/EBP-delta, NF-IL6-beta
Ensembl gene	ENSG00000221869
Ensembl biotype	protein_coding
OMIM	116898
Entrez	1052

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000408965

RefSeq mRNA: 1 — MANE Select: NM_005195 NM_005195

CCDS: CCDS6142

Canonical transcript exons

ENST00000408965 — 1 exons

Exon	Start	End
ENSE00002241668	47736913	47738164

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 184.9316 / max 4350.4643, expressed in 1772 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92970	183.4638	1771
92971	1.4678	920

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.90	gold quality
vena cava	UBERON:0004087	99.89	gold quality
lower lobe of lung	UBERON:0008949	99.75	gold quality
trachea	UBERON:0003126	99.59	gold quality
cardia of stomach	UBERON:0001162	99.58	gold quality
type B pancreatic cell	CL:0000169	99.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.50	gold quality
olfactory bulb	UBERON:0002264	99.40	gold quality
cartilage tissue	UBERON:0002418	99.39	gold quality
mucosa of stomach	UBERON:0001199	99.37	gold quality
trigeminal ganglion	UBERON:0001675	99.36	gold quality
right ovary	UBERON:0002118	99.34	gold quality
parotid gland	UBERON:0001831	99.33	gold quality
left uterine tube	UBERON:0001303	99.27	gold quality
nipple	UBERON:0002030	99.26	gold quality
left ovary	UBERON:0002119	99.25	gold quality
saphenous vein	UBERON:0007318	99.22	gold quality
mucosa of urinary bladder	UBERON:0001259	99.13	gold quality
omental fat pad	UBERON:0010414	99.13	gold quality
peritoneum	UBERON:0002358	99.12	gold quality
dorsal root ganglion	UBERON:0000044	99.11	gold quality
renal medulla	UBERON:0000362	99.10	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.03	gold quality
tibial nerve	UBERON:0001323	99.00	gold quality
cauda epididymis	UBERON:0004360	98.98	gold quality
pylorus	UBERON:0001166	98.97	gold quality
right lung	UBERON:0002167	98.93	gold quality
popliteal artery	UBERON:0002250	98.92	gold quality
tibial artery	UBERON:0007610	98.92	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-CURD-126	yes	4048.91
E-GEOD-149689	yes	1780.98
E-HCAD-30	yes	288.75
E-MTAB-9154	yes	265.04
E-CURD-122	yes	75.68
E-HCAD-1	yes	74.61
E-HCAD-4	yes	70.24
E-MTAB-8410	yes	57.37
E-HCAD-6	yes	49.93
E-CURD-46	yes	41.90
E-GEOD-134144	yes	28.81
E-GEOD-135922	yes	24.60
E-CURD-88	yes	21.33
E-MTAB-9467	yes	15.88
E-MTAB-9067	yes	15.12

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

107 targets.

Target	Regulation
A2M
ADAM2
ADIPOQ
ADRA1D
ALB
ALOX5AP	Unknown
AMELX	Activation
APOC3
AR
BCL2L11
BGLAP	Activation
C3	Unknown
CAMKK2
CASP3
CASP8	Unknown
CCL2	Activation
CCL20	Activation
CCL5	Activation
CCN2	Activation
CCN5	Repression
CCND1	Activation
CD74
CDC27
CEBPA	Activation
CEBPB	Activation
CEBPD
CFTR	Unknown
CIITA
COL1A1
CSF1R

JASPAR motifs

Motif	Name	Family
MA0836.1	CEBPD	CEBP-related
MA0836.2	CEBPD	CEBP-related
MA0836.3	CEBPD	CEBP-related

JASPAR matrix evidence (PMIDs): PMID:8632009

Upstream regulators (CollecTRI, top): AR, CEBPB, CEBPD, CEBPG, DDIT3, GATA4, IRF6, JDP2, JUN, MAX, MYC, NFIA, NFKB, NFKBID, NR3C1, REL, RUNX2, SOX9, SP1, STAT1, STAT3, SUZ12, TBX2, TFCP2, YY1, ZBTB17

miRNA regulators (miRDB)

37 targeting CEBPD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-6834-3P	98.16	65.77	551

Literature-anchored findings (GeneRIF, showing 40)

• These findings provide new insight into the regulation of cyclooxygenase-2 promoter by an interplay between two opposite beta isoforms and p300 co-activator. (PMID:11741938)
• A single nucleotide polymorphism in the CEBPD gene was found in 2.9% of patients studied. (PMID:11851384)
• posttranscriptional and posttranslational regulation in G0 growth-arrested mammary epithelial cells (PMID:12554732)
• Expression levels of C/EBPdelta in breast tumors were correlated with clinicopathological tumor parameters, expression of estrogen and progesterone receptors (ER, PR), Ki67 immunostaining, and expression of 7 cell-cycle regulatory proteins. (PMID:12825852)
• C/EBPdelta has a role in abolishing CBP phosphorylation as well as transcriptional activation and could be important in C/EBP-mediated transcription (PMID:12857754)
• AD tissue sections revealed profuse C/EBPdelta staining of astrocytes, particularly reactive astrocytes surrounding amyloid beta peptide deposits. Substantially less immunoreactivity was observed in comparable sections from controls. (PMID:15212823)
• results indicate that the C/EBPdelta gene is controlled at multiple levels, consistent with a role for C/EBPdelta in cell cycle control and/or cell fate determination. (PMID:15389878)
• results demonstrate that “loss of function” alterations in the pSTAT3/C/EBPdelta growth inhibitory signal transduction pathway are relatively common in breast cancer cell lines (PMID:15389879)
• C EBP delta is a downstream mediator of IL-6 induced growth inhibition of prostate cancer cells. (PMID:15486993)
• Expression of C/EBPdelta in BCR-ABL-positive leukemic cells in blast crisis is sufficient for neutrophil differentiation. (PMID:15674331)
• IL-6 increases hepatic PAI-1 expression mediated by the -232- to -210-bp region of the promoter containing a C/EBPdelta binding site. (PMID:15718495)
• the PI3-kinase/p38(MAPK)/CREB pathway contributes to the EGF activation of NF-IL6beta gene expression (PMID:15901830)
• Small interfering RNA of C/EBPdelta suppressed COX-2 expression, strengthening the role of C/EBPdelta in COX-2 gene transcription. (PMID:16195339)
• Reduced C/EBPdelta gene expression is associated with breast tumors (PMID:16322893)
• IL-1 and IL-6 exert directionally similar effects on PAI-1 expression, but the induction involves distinct signaling pathways with a final common mediator, C/EBPdelta. (PMID:16914534)
• Reverse-transcription polymerase chain reaction confirmed increased expression of GADD45A, BTG2, PDE4B, and CEBPD and downregulation of TOB1 in skeletal muscle intradialysis. (PMID:16997058)
• C/EBPdelta is a novel tumor suppressor gene in acute myeloid leukemia that is silenced by promoter methylation. (PMID:17234736)
• C/EBPdelta ubiquitination is not required for proteasome-mediated C/EBPdelta degradation and the presence of ubiquitin does not increase C/EBPdelta degradation by the proteasome. (PMID:17373909)
• C/EBPdelta, but not DeltaNp63alpha, indefinitely promotes holoclone self-renewal and prevents clonal evolution, suggesting that self-renewal and proliferation are distinct, albeit related, processes in limbal stem cells. (PMID:17562792)
• Reciprocal regulation of p63 by C/EBP delta in human keratinocytes (PMID:17903252)
• that interactions between C/EBPs and HDAC1 negatively regulate C/EBPdelta-dependent haptoglobin expression in intestinal epithelial cells. (PMID:17910034)
• Genetic variations in the C/EBP-delta might play a role in some metabolic phenotypes. (PMID:18370833)
• YY1 physically interacts with SUZ12 and can act as a mediator to recruit the polycomb group proteins and DNA methyltransferases to participate in the CEBPD gene silencing process (PMID:18753137)
• These results suggest a potentially crucial role for NF-kappaB in the IL-1-induced expression of C/EBPdelta, and thereby downstream acute phase protein genes regulated by this transcription factor. (PMID:19800021)
• C/EBPdelta expression may prevent the development of recurrences by inhibition of neoplastic growth in meningiomas (PMID:19806320)
• Data show that C/EBPalpha replaces C/EBPbeta and C/EBPdelta as a regulator of SREBP1c expression in maturing adipocytes. (PMID:19811452)
• Expression of CEBPD reduces cisplatin-induced reactive oxygen species and apoptosis in NTUB1 carcinoma cells by inducing the expression of copper/zinc-superoxide dismutase via direct promoter transactivation. (PMID:20385105)
• Common allelic variants in CEBPD were not associated with obesity phenotypes in healthy White Northern European families. (PMID:20460359)
• found that C/EBPdelta promotes monoubiquitination of the Fanconi anemia complementation group D2 protein (FANCD2), which is necessary for its function in replication-associated DNA repair (PMID:20805509)
• C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity. (PMID:20829351)
• HMDB kills cancer cells through activation of CEBPD pathways. (PMID:20971808)
• Data indicate that C/EBPdelta plays a role in late stages of keratinocyte differentiation. (PMID:21072181)
• CEBPD inhibits FBXW7 expression and augments HIF-1 alpha expression and activity under hypoxia (PMID:21076392)
• This study provides the first demonstration of a role for astrocytic CEBPD and the CEBPD-regulated molecule PTX3 in the accumulation of damaged neurons, which is a hallmark of AD pathogenesis. (PMID:21112127)
• new function of CEBP-delta in lymphangiogenesis through regulation of VEGFR3 signaling in lymphatic endothelial cells (PMID:21666710)
• Src kinase activity downregulates C/EBP-delta protein but not mRNA levels through a SIAH2 E3 ligase-dependent mechanism. (PMID:22037769)
• Findings suggest that CEBPD and its downstream effectors could be biomarkers for the diagnosis of RA and potentially serve as therapeutic targets for RA therapy. (PMID:23028973)
• CEBPD supports inflammatory signaling through activation of the TLR4 gene; and is downregulated by FBXW7 alpha following phosphorylation by GSK-3 beta. (PMID:23575666)
• The FRA8I fragile site includes KIAA0146, CEBPD and PRKDC and may have a role in colorectal cancer (PMID:23603433)
• the inflammatory PGE-HuR-C/EBPdelta axis in macrophages promotes tumor progression by preventing the phagocytosis of tumor cells and inducing immunosuppressive cytokine production. (PMID:23861541)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cebpd	ENSDARG00000087303
mus_musculus	Cebpd	ENSMUSG00000071637
rattus_norvegicus	Cebpd	ENSRNOG00000086729
drosophila_melanogaster	slbo	FBGN0005638
caenorhabditis_elegans		WBGENE00016997
caenorhabditis_elegans	zip-4	WBGENE00021552

Paralogs (4): CEBPE (ENSG00000092067), CEBPG (ENSG00000153879), CEBPB (ENSG00000172216), CEBPA (ENSG00000245848)

Protein

Protein identifiers

CCAAT/enhancer-binding protein delta — P49716 (reviewed: P49716)

Alternative names: Nuclear factor NF-IL6-beta

All UniProt accessions (1): P49716

UniProt curated annotations — full annotation on UniProt →

Function. Transcription activator that recognizes two different DNA motifs: the CCAAT homology common to many promoters and the enhanced core homology common to many enhancers. Important transcription factor regulating the expression of genes involved in immune and inflammatory responses. Transcriptional activator that enhances IL6 transcription alone and as heterodimer with CEBPB.

Subunit / interactions. Binds DNA as a homodimer and as a heterodimer. Can form stable heterodimers with CEBPB. Can form stable heterodimers with CEBPA and CEBPE. Directly interacts with SPI1/PU.1; this interaction does not affect DNA-binding properties of each partner. Interacts with PRDM16.

Subcellular location. Nucleus.

Similarity. Belongs to the bZIP family. C/EBP subfamily.

RefSeq proteins (1): NP_005186* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR016468	C/EBP_chordates	Family
IPR031106	C/EBP	Family
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF07716

UniProt features (19 total): region of interest 5, compositionally biased region 4, sequence conflict 3, initiator methionine 1, chain 1, modified residue 1, cross-link 1, sequence variant 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49716-F1	67.03	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 120

Mutagenesis-validated functional residues (1):

Position	Phenotype
120	loss of sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9610379	HCMV Late Events
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-449147	Signaling by Interleukins
R-HSA-5663205	Infectious disease
R-HSA-9609646	HCMV Infection
R-HSA-9824446	Viral Infection Pathways
R-HSA-9843745	Adipogenesis

MSigDB gene sets: 361 (showing top): REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, KOBAYASHI_EGFR_SIGNALING_24HR_UP, WALLACE_PROSTATE_CANCER_RACE_UP, MCLACHLAN_DENTAL_CARIES_UP, PID_HNF3B_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, ZHAN_MULTIPLE_MYELOMA_MF_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MENSE_HYPOXIA_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_128, GOBP_OSTEOBLAST_DIFFERENTIATION, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, SHEPARD_BMYB_MORPHOLINO_DN

GO Biological Process (12): hematopoietic progenitor cell differentiation (GO:0002244), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), fat cell differentiation (GO:0045444), regulation of cell differentiation (GO:0045595), positive regulation of osteoblast differentiation (GO:0045669), negative regulation of DNA-templated transcription (GO:0045892), inner ear development (GO:0048839), integrated stress response signaling (GO:0140467), DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), identical protein binding (GO:0042802), sequence-specific double-stranded DNA binding (GO:1990837), transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Adipogenesis	1
Signaling by Interleukins	1
HCMV Infection	1
Immune System	1
Cytokine Signaling in Immune system	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	3
regulation of DNA-templated transcription	3
DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
hemopoiesis	1
regulation of developmental process	1
regulation of cellular process	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
negative regulation of RNA biosynthetic process	1
ear development	1
anatomical structure development	1
cellular response to stress	1
intracellular signaling cassette	1
gene expression	1
RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEBPD	CEBPB	P17676	965
CEBPD	CELF1	Q92879	908
CEBPD	CELF3	Q5SZQ8	900
CEBPD	CELF2	O95319	893
CEBPD	CELF4	Q9BZC1	891
CEBPD	TNNT2	P45379	832
CEBPD	CELF5	Q8N6W0	831
CEBPD	CREB1	P16220	818
CEBPD	SMAD4	Q13485	811
CEBPD	CELF6	Q96J87	797
CEBPD	KLF5	Q13887	797
CEBPD	MBNL1	Q9NR56	780
CEBPD	SLC5A8	Q8N695	777
CEBPD	SLC5A12	Q1EHB4	773
CEBPD	SLC22A12	Q96S37	763

IntAct

38 interactions, top by confidence:

A	B	Type	Score
FANCD2	CEBPD	psi-mi:“MI:0914”(association)	0.610
CEBPD	FANCD2	psi-mi:“MI:0914”(association)	0.610
CEBPD	FANCD2	psi-mi:“MI:0915”(physical association)	0.610
IPO4	CEBPD	psi-mi:“MI:0914”(association)	0.610
CEBPD	IPO4	psi-mi:“MI:0915”(physical association)	0.610
CEBPD	IPO4	psi-mi:“MI:0914”(association)	0.610
CEBPD	CEBPB	psi-mi:“MI:0407”(direct interaction)	0.590
CEBPD	CEBPA	psi-mi:“MI:0407”(direct interaction)	0.440
CEBPA	CEBPD	psi-mi:“MI:0407”(direct interaction)	0.440
CEBPD	CEBPD	psi-mi:“MI:0407”(direct interaction)	0.440
CEBPG	CEBPD	psi-mi:“MI:0407”(direct interaction)	0.440
DDIT3	CEBPD	psi-mi:“MI:0407”(direct interaction)	0.440
ATF4	CEBPD	psi-mi:“MI:0407”(direct interaction)	0.440
BATF3	CEBPD	psi-mi:“MI:0407”(direct interaction)	0.440
CEBPD	CEBPG	psi-mi:“MI:0407”(direct interaction)	0.440
CEBPD	DDIT3	psi-mi:“MI:0407”(direct interaction)	0.440
BATF	CEBPD	psi-mi:“MI:0407”(direct interaction)	0.440
CEBPD	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
	CEBPD	psi-mi:“MI:0915”(physical association)	0.400
CEBPD		psi-mi:“MI:0915”(physical association)	0.400
CEBPD	XPO1	psi-mi:“MI:0914”(association)	0.350
CEBPD	EEF1D	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): CEBPD (Biochemical Activity), CEBPD (Biochemical Activity), CEBPD (Synthetic Growth Defect), FBXW7 (Affinity Capture-Western), CEBPD (Affinity Capture-Western), CEBPD (Biochemical Activity), UBC (Affinity Capture-Western), CEBPD (Biochemical Activity), CEBPD (Protein-peptide), CEBPD (Affinity Capture-MS), BASP1 (Affinity Capture-MS), CCDC85B (Affinity Capture-MS), CDC37 (Affinity Capture-MS), EEF1B2 (Affinity Capture-MS), EEF1D (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6AGW3, A2A9A2, A6NMB9, A8MYZ6, E9PZZ1, J3QK54, O02755, O02756, O35392, O35767, O60548, O70220, P05554, P17676, P21272, P28033, P35713, P42582, P49715, P49716, P52952, P53566, P58012, Q12952, Q13461, Q14526, Q60843, Q61345, Q63244, Q63250, Q6BEB4, Q6VFT5, Q6VFT6, Q6ZQN5, Q70KY4, Q8IU81, Q8MIP2, Q8NDY6, Q8R2I0, Q98937

Diamond homologs: O02754, O02755, O02756, O77728, P05554, P17676, P21272, P26801, P28033, P49715, P49716, P53566, P53567, P53568, P56261, Q00322, Q02638, Q03484, Q05826, Q15744, Q3T0B9, Q6PZD9, Q9N0J3

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
SOX9	“down-regulates quantity by repression”	CEBPD	“transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	SOD1	“transcriptional regulation”
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	CEBPD	polyubiquitination
KLHL9	“down-regulates quantity by destabilization”	CEBPD	binding
GSK3B	“down-regulates quantity by destabilization”	CEBPD	phosphorylation
dexamethasone	“up-regulates quantity by expression”	CEBPD
SMAD3/SMAD4	down-regulates	CEBPD	binding
CEBPD	“up-regulates quantity by expression”	KLF5	“transcriptional regulation”
NR3C1	“up-regulates quantity”	CEBPD	“transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	PPARG	“transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	CCL20	“transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	TNFAIP6	“transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	CXCL1	“transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	IL23A	“transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	MSTN	“transcriptional regulation”
STAT3	“up-regulates quantity by expression”	CEBPD	“transcriptional regulation”
CSNK2A1	“up-regulates activity”	CEBPD	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Response of EIF2AK1 (HRI) to heme deficiency	5	223.1×	1e-09
ATF4 activates genes in response to endoplasmic reticulum stress	5	127.5×	1e-08
Response of EIF2AK4 (GCN2) to amino acid deficiency	5	34.6×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	7	289.1×	3e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

68 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4 predictions. Top by Δscore:

Variant	Effect	Δscore
8:47737736:C:CA	acceptor_gain	0.2500
8:47738138:CT:C	acceptor_gain	0.2500
8:47737455:CTT:C	donor_gain	0.2000
8:47738144:G:GA	acceptor_gain	0.2000

AlphaMissense

1731 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:47737496:G:T	R209S	1.000
8:47737500:C:A	K207N	1.000
8:47737500:C:G	K207N	1.000
8:47737510:G:T	A204D	1.000
8:47737515:G:C	N202K	1.000
8:47737515:G:T	N202K	1.000
8:47737518:G:C	N201K	1.000
8:47737518:G:T	N201K	1.000
8:47737519:T:A	N201I	1.000
8:47737520:T:C	N201D	1.000
8:47737529:G:T	R198S	1.000
8:47737390:A:G	L244P	0.999
8:47737402:A:G	L240P	0.999
8:47737423:A:G	L233P	0.999
8:47737444:A:G	L226P	0.999
8:47737477:C:G	R215P	0.999
8:47737482:C:A	K213N	0.999
8:47737482:C:G	K213N	0.999
8:47737487:C:G	A212P	0.999
8:47737488:C:A	K211N	0.999
8:47737488:C:G	K211N	0.999
8:47737496:G:A	R209C	0.999
8:47737497:G:C	S208R	0.999
8:47737497:G:T	S208R	0.999
8:47737499:T:G	S208R	0.999
8:47737502:T:C	K207E	0.999
8:47737504:C:G	R206P	0.999
8:47737505:G:T	R206S	0.999
8:47737511:C:G	A204P	0.999
8:47737516:T:A	N202I	0.999

dbSNP variants (sampled 300 via entrez): RS1000925679 (8:47738417 G>A), RS1000988488 (8:47738875 C>T), RS1002346085 (8:47738940 ACACCGC>A), RS1002377249 (8:47738675 G>A), RS1002417459 (8:47737165 C>G,T), RS1002469612 (8:47737460 G>C), RS1002678274 (8:47740032 C>T), RS1005769851 (8:47736761 C>G), RS1006074015 (8:47737979 C>A,T), RS1006154619 (8:47736863 C>T), RS1006573377 (8:47737229 G>A), RS1006838506 (8:47740002 A>C), RS1007272418 (8:47738955 C>G,T), RS1007735564 (8:47739064 C>T), RS1008593414 (8:47739163 T>A,C)

Disease associations

OMIM: gene MIM:116898 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST004600_41	Eosinophil percentage of white cells	9.000000e-14
GCST004606_165	Eosinophil count	6.000000e-13
GCST004608_105	Granulocyte percentage of myeloid white cells	2.000000e-19
GCST004609_45	Monocyte percentage of white cells	1.000000e-17
GCST004617_16	Eosinophil percentage of granulocytes	2.000000e-16
GCST004623_115	Neutrophil percentage of granulocytes	1.000000e-17
GCST004624_124	Sum eosinophil basophil counts	3.000000e-13
GCST004625_107	Monocyte count	2.000000e-13
GCST004633_76	Neutrophil percentage of white cells	4.000000e-13
GCST90002379_118	Basophil count	8.000000e-18
GCST90002380_58	Basophil percentage of white cells	2.000000e-21
GCST90002381_372	Eosinophil count	3.000000e-26
GCST90002382_172	Eosinophil percentage of white cells	3.000000e-30
GCST90002389_176	Lymphocyte percentage of white cells	8.000000e-10
GCST90002393_571	Monocyte count	1.000000e-34
GCST90002394_277	Monocyte percentage of white cells	9.000000e-50
GCST90002398_400	Neutrophil count	8.000000e-12
GCST90002399_196	Neutrophil percentage of white cells	1.000000e-32

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007992	basophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

115 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, increases methylation, affects cotreatment	6
Particulate Matter	decreases expression, increases abundance, increases expression, increases reaction, affects cotreatment	6
Estradiol	increases expression, decreases expression, affects expression, affects cotreatment	5
Air Pollutants	increases expression, decreases expression, increases abundance	4
Tetrachlorodibenzodioxin	increases expression, decreases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Progesterone	affects cotreatment, increases expression	3
Tretinoin	affects cotreatment, decreases expression, increases expression	3
methylparaben	decreases expression	2
Resveratrol	decreases expression, increases expression	2
Arsenic Trioxide	increases expression, affects cotreatment, decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Cisplatin	decreases expression, increases expression	2
Diethylstilbestrol	increases expression	2
Oxygen	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression	2
Genistein	increases expression, decreases expression	2
Glupearl 19S	increases expression	1
bisphenol F	affects cotreatment, increases methylation	1
TAK-243	decreases sumoylation	1
fluorene-9-bisphenol	decreases expression	1
methylmercuric chloride	increases expression	1
quinomethionate	affects expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
alpha-naphthoflavone	increases expression, increases reaction	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0P6	SEES3-1V human CEBPD, clone1	Embryonic stem cell	Male
CVCL_A0P7	SEES3-1V human CEBPD, clone2	Embryonic stem cell	Male
CVCL_A0P8	SEES3-1V human CEBPD, clone3	Embryonic stem cell	Male
CVCL_D1VQ	Abcam A-549 CEBPD KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.