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
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.59 (intermediate), LOEUF 0.99 (unconstrained)
• Transcription factor: yes — 107 downstream targets (CollecTRI)
• MANE Select transcript: NM_005195
• Interaction hub: 2,378 STRING partners (top 5% of genes corpus-wide)
• Notable: 68 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 2 — 1 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000408965

ENST00000408965, ENST00001125467

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.

Highest expression (Bgee): pericardium, vena cava, lower lobe of lung, trachea, cardia of stomach.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CEBPD is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	2.9e-07	-0.73	8:47739071:A:G
Skin Sun Exposed Lower leg	eqtl	7.1e-03	+0.31	8:48270344:C:T
Pancreas	eqtl	7.7e-03	-0.39	8:48106230:G:A
Artery Aorta	eqtl	1.5e-02	-0.34	8:48382267:G:C
Adipose Visceral Omentum	eqtl	2.6e-02	+0.41	8:46844292:C:T
Cells Cultured fibroblasts	eqtl	4.0e-02	-0.08	8:47362088:G:A

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 295 tissues 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
mammary duct	UBERON:0001765	98.91	gold quality
urethra	UBERON:0000057	98.82	gold quality
cervix squamous epithelium	UBERON:0006922	98.79	silver quality
pharyngeal mucosa	UBERON:0000355	98.73	gold quality
tibialis anterior	UBERON:0001385	98.72	gold quality
decidua	UBERON:0002450	98.69	gold quality
adult organism	UBERON:0007023	98.69	gold quality
upper lobe of lung	UBERON:0008948	98.62	gold quality
monocyte	CL:0000576	98.60	gold quality
layer of synovial tissue	UBERON:0007616	98.60	gold quality
seminal vesicle	UBERON:0000998	98.57	gold quality
mononuclear cell	CL:0000842	98.55	gold quality
upper lobe of left lung	UBERON:0008952	98.55	gold quality
leukocyte	CL:0000738	98.48	gold quality
lower esophagus mucosa	UBERON:0035834	98.48	gold quality
calcaneal tendon	UBERON:0003701	98.47	gold quality
heart right ventricle	UBERON:0002080	98.38	gold quality
aorta	UBERON:0000947	98.36	gold quality
epithelium of mammary gland	UBERON:0003244	98.34	gold quality
mammalian vulva	UBERON:0000997	98.29	gold quality
ectocervix	UBERON:0012249	98.25	gold quality
right lobe of thyroid gland	UBERON:0001119	98.23	gold quality
pituitary gland	UBERON:0000007	98.21	gold quality
body of tongue	UBERON:0011876	98.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.19	gold quality
coronary artery	UBERON:0001621	98.15	gold quality
left coronary artery	UBERON:0001626	98.14	gold quality
fundus of stomach	UBERON:0001160	98.10	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.09	gold quality
blood	UBERON:0000178	98.08	gold quality
synovial joint	UBERON:0002217	98.08	gold quality
adenohypophysis	UBERON:0002196	98.06	gold quality
right atrium auricular region	UBERON:0006631	97.97	gold quality
periodontal ligament	UBERON:0008266	97.97	gold quality
descending thoracic aorta	UBERON:0002345	97.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.92	gold quality
lower esophagus	UBERON:0013473	97.90	gold quality
spleen	UBERON:0002106	97.86	gold quality
right lobe of liver	UBERON:0001114	97.85	gold quality
thymus	UBERON:0002370	97.85	gold quality
cardiac atrium	UBERON:0002081	97.83	gold quality
caput epididymis	UBERON:0004358	97.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.78	gold quality
trabecular bone tissue	UBERON:0002483	97.77	gold quality
adipose tissue	UBERON:0001013	97.73	gold quality
penis	UBERON:0000989	97.72	gold quality
left lobe of thyroid gland	UBERON:0001120	97.71	gold quality
diaphragm	UBERON:0001103	97.68	gold quality
skin of abdomen	UBERON:0001416	97.64	gold quality
ascending aorta	UBERON:0001496	97.63	gold quality
connective tissue	UBERON:0002384	97.63	gold quality
thoracic aorta	UBERON:0001515	97.61	gold quality
body of stomach	UBERON:0001161	97.60	gold quality
nasal cavity epithelium	UBERON:0005384	97.59	gold quality
nasal cavity mucosa	UBERON:0001826	97.52	gold quality
sigmoid colon	UBERON:0001159	97.46	gold quality
granulocyte	CL:0000094	97.45	gold quality
endocervix	UBERON:0000458	97.45	gold quality
metanephros cortex	UBERON:0010533	97.41	gold quality
bronchus	UBERON:0002185	97.38	gold quality
skin of leg	UBERON:0001511	97.37	gold quality
tongue	UBERON:0001723	97.33	gold quality
epithelium of bronchus	UBERON:0002031	97.30	gold quality
right coronary artery	UBERON:0001625	97.28	gold quality
corpus epididymis	UBERON:0004359	97.27	gold quality
adult mammalian kidney	UBERON:0000082	97.24	gold quality
nephron tubule	UBERON:0001231	97.22	gold quality
cranial nerve II	UBERON:0000941	97.18	gold quality
lung	UBERON:0002048	97.17	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Vagina	tissue	251.2
Pituitary gland	tissue	212.0
Adipose tissue	tissue	114.1
Liver	tissue	98.0
Choroid plexus	tissue	78.3
Hippocampus	tissue	60.8
Appendix	tissue	58.7
Spleen	tissue	58.6
Ovary	tissue	56.8
Adrenal gland	tissue	56.6
Locus coeruleus	tissue	52.7
Urinary bladder	tissue	52.4
Placenta	tissue	47.0
Lung	tissue	41.2
Colon	tissue	39.5
Small intestine	tissue	39.3
Stomach 1	tissue	36.8
Nucleus accumbens	tissue	36.1
Prostate	tissue	35.6
Hippocampal formation	tissue	33.3
Bone marrow	tissue	32.4
Spinal cord	tissue	31.7
Kidney	tissue	31.4
Pancreas	tissue	30.2
Superior colliculi	tissue	27.6
Skeletal muscle	tissue	26.5
Breast	tissue	26.4
Postcentral gyrus	tissue	26.3
Duodenum	tissue	25.1
Cervix	tissue	22.3
Smooth muscle	tissue	20.2
Tongue	tissue	20.2
Seminal vesicle	tissue	18.3
Thymus	tissue	17.3
Fallopian tube	tissue	16.0
Retina	tissue	15.7
Endometrium 1	tissue	15.4
Salivary gland	tissue	14.0
Gallbladder	tissue	13.8
Substantia nigra	tissue	13.3
Esophagus	tissue	13.0
Rectum	tissue	11.4
Skin 1	tissue	9.6
Medulla oblongata	tissue	8.7
Lymph node	tissue	8.2
Midbrain	tissue	7.7
Heart muscle	tissue	7.5
Pons	tissue	7.3
Parathyroid gland	tissue	7.1
Thalamus	tissue	6.6
Amygdala	tissue	6.4
Olfactory bulb	tissue	6.4
Septum	tissue	6.4
Hypothalamus	tissue	6.2
Tonsil	tissue	6.2
Thyroid gland	tissue	5.3
Entorhinal cortex	tissue	4.4
Cerebral cortex	tissue	4.2
Temporal cortex	tissue	4.2
Periaqueductal gray	tissue	4.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (474.6), Area postrema (157.3), Supraoptic nucleus (121.1), Nucleus raphe pallidus (115.5), Peritrigeminal nucleus (91.5).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

showing 30 of 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
UN0505.1	ERF::CEBPD	Ets-related,CEBP-related
UN0505.2	ERF::CEBPD	Ets-related,CEBP-related
UN0510.1	ETV2::CEBPD	Ets-related,CEBP-related
UN0510.2	ETV2::CEBPD	Ets-related,CEBP-related
UN0523.1	ETV5::CEBPD	Ets-related,CEBP-related
UN0523.2	ETV5::CEBPD	Ets-related,CEBP-related
UN0527.1	FLI1::CEBPD	Ets-related,CEBP-related
UN0527.2	FLI1::CEBPD	Ets-related,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)

Targeting CEBPD by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 37 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.594, LOEUF 0.99, missense Z -2.63 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000408965 — one region, missense o/e 1.00.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:103573) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 15 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal branching of the mammary ductal tree	1
abnormal contextual conditioning behavior	1
decreased inflammatory response	1
abnormal respiratory system physiology	1
abnormal brown adipose tissue morphology	1
abnormal cell differentiation	1
decreased susceptibility to injury	1
abnormal epididymal fat pad morphology	1
abnormal cytokine level	1
decreased blood uric acid level	1
abnormal mammary gland epithelium morphology	1
abnormal urine homeostasis	1
increased urine uric acid level	1
increased mammary gland epithelial cell proliferation	1
decreased circulating lactate level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Ovis aries	O77728	95.4%	Diamond
Bos taurus	O02754	93.6%	Diamond
Gallus gallus	Q05826	72.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SPIDR	protein-coding	23514
MCM4	protein-coding	4173
PRKDC	protein-coding	5591
UBE2V2-AS1	ncRNA	105375819
UBE2V2	protein-coding	7336

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Basic domains

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IF approved

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)

Type	Positions
N-acetylserine	2
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	120

Mutagenesis-validated functional residues (1)

Position	Phenotype
120	loss of sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 12; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

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

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 (7): regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), regulation of cell differentiation (GO:0045595), 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

9 top-level categories:

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

36 GO namespaces:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	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
nuclear lumen	1
transcription regulator complex	1
nuclear protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
sequence-specific double-stranded DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,378 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEBPD	CELF3	Q5SZQ8	897
CEBPD	CELF1	Q92879	885
CEBPD	CELF4	Q9BZC1	881
CEBPD	CELF2	O95319	870
CEBPD	CELF5	Q8N6W0	833
CEBPD	TNNT2	P45379	814
CEBPD	CELF6	Q96J87	788
CEBPD	SLC5A8	Q8N695	769
CEBPD	MBNL1	Q9NR56	766
CEBPD	SLC5A12	Q1EHB4	765
CEBPD	SLC22A12	Q96S37	756
CEBPD	PPARG	P37231	717
CEBPD	RRM2	P31350	640
CEBPD	STAT3	P40763	620
CEBPD	DMPK	Q09013	616

IntAct

Human interaction partners of CEBPD in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

15 partners by confidence:

Partner	Interaction type	MIscore	Records
FANCD2	association	0.610	6
IPO4	association	0.610	4
CEBPB	direct interaction	0.590	1
ATF4	direct interaction	0.440	2
CEBPA	direct interaction	0.440	2
CEBPG	direct interaction	0.440	2
DDIT3	direct interaction	0.440	2
BATF	direct interaction	0.440	1
BATF3	direct interaction	0.440	1
EEF1D	association	0.350	1
ESYT2	association	0.350	1
IGF2BP3	association	0.350	1
MYO1C	association	0.350	1
PTGES	association	0.350	1
XPO1	association	0.350	1

BioGRID (79 interactions; top human partners by supporting records): TRIM26 (Affinity Capture-Western; 5 records), FANCD2 (Affinity Capture-MS; 4 records), HDAC1 (Affinity Capture-Western; 4 records), FBXW7 (Affinity Capture-Western; 3 records), IPO4 (Affinity Capture-MS; 3 records), ATF4 (Affinity Capture-Western; 2 records), ATF6 (Affinity Capture-Western; 2 records), CEBPB (Reconstituted Complex; 2 records), FOXP1 (Affinity Capture-Western; 2 records), HDAC3 (Affinity Capture-Western; 2 records), SIAH2 (Affinity Capture-Western; 2 records), SMAD3 (Reconstituted Complex; 2 records), SMAD4 (Reconstituted Complex; 2 records), SOX2 (Affinity Capture-Western; 2 records), XBP1 (Affinity Capture-Western; 2 records)

SIGNOR signaling

showing 17 of 19 signaling 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 15 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.

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	7	327.7×	7e-15

Disease & clinical

Genetic variants

Variant evidence for CEBPD: 68 ClinVar records (0 pathogenic / likely pathogenic); 18 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 17 predictions of 33):

Position(s)	Effect	Δscore	Sites
8:47737313–47737314	donor_loss	0.3800	6
8:47737312	donor_loss	0.3700	2
8:47737131	donor_gain	0.3600
8:47737315	donor_loss	0.3600
8:47737315	donor_loss	0.3500	2
8:47737182	donor_gain	0.3400
8:47737312	donor_loss	0.3300
8:47737468	donor_gain	0.3300
8:47737501	acceptor_gain	0.3000
8:47737057	donor_gain	0.2900

AlphaMissense

589 missense substitutions predicted likely pathogenic (of 1,731 scored), across 135 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M219	9	0.856	0.978
N201	8	0.999	1.000
N202	8	0.998	1.000
S208	8	0.989	0.999
D60	8	0.986	0.995
N230	8	0.986	0.996
F86	8	0.980	0.997
F82	8	0.979	0.997
D79	8	0.977	0.998
D84	8	0.962	0.990
F61	8	0.961	0.999
D210	8	0.954	0.991
F251	8	0.950	0.993
D66	8	0.808	0.975
D55	8	0.805	0.946
E56	7	0.948	0.986
C77	7	0.932	0.982
E199	7	0.932	0.983
S62	7	0.917	0.993
E80	7	0.898	0.980

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Rectum Adenocarcinoma (validation)	favorable	5.54e-05
Bladder Urothelial Carcinoma (TCGA)	favorable	0.000187
Breast Invasive Carcinoma (TCGA)	favorable	0.000333
Kidney Chromophobe (TCGA)	favorable	0.000919
Glioblastoma Multiforme (validation)	unfavorable	0.000994

Disease associations

OMIM: gene MIM:116898 | disease phenotypes:

GWAS associations

18 associations:

Study	Trait	p-value
GCST90002394_537	Monocyte percentage of white cells	9e-50
GCST90002393_521	Monocyte count	1e-34
GCST90002399_11	Neutrophil percentage of white cells	1e-32
GCST90002382_215	Eosinophil percentage of white cells	3e-30
GCST90002381_271	Eosinophil count	3e-26
GCST90002380_69	Basophil percentage of white cells	2e-21
GCST004608_179	Granulocyte percentage of myeloid white cells	2e-19
GCST90002379_18	Basophil count	8e-18
GCST004609_70	Monocyte percentage of white cells	1e-17
GCST004623_105	Neutrophil percentage of granulocytes	1e-17
GCST004617_16	Eosinophil percentage of granulocytes	2e-16
GCST004600_41	Eosinophil percentage of white cells	9e-14
GCST004625_82	Monocyte count	2e-13
GCST004624_124	Sum eosinophil basophil counts	3e-13
GCST004633_75	Neutrophil percentage of white cells	4e-13
GCST004606_115	Eosinophil count	6e-13
GCST90002398_120	Neutrophil count	8e-12
GCST90002389_376	Lymphocyte percentage of white cells	8e-10

EFO canonical traits (from GWAS)

12 canonical traits:

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 (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects cotreatment, increases expression	6
Particulate Matter	decreases expression, increases abundance, increases expression, increases reaction, affects cotreatment	6
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	5
Air Pollutants	decreases expression, increases abundance, increases expression	4
Tetrachlorodibenzodioxin	decreases expression, increases 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	increases expression, decreases 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	decreases expression, increases 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	affects binding, increases activity, increases expression	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)

Via MONDO — disease-level, not drug-specific.