ECD

Summary

ECD (ecdysoneless cell cycle regulator, HGNC:17029) is a protein-coding gene on chromosome 10q22.2, encoding Protein ecdysoneless homolog (O95905). Regulator of p53/TP53 stability and function. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

Enables histone acetyltransferase binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm.

Source: NCBI Gene 11319 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 111 total
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_007265

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17029
Approved symbol	ECD
Name	ecdysoneless cell cycle regulator
Location	10q22.2
Locus type	gene with protein product
Status	Approved
Aliases	hSGT1, GCR2
Ensembl gene	ENSG00000122882
Ensembl biotype	protein_coding
OMIM	616464
Entrez	11319

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000372979, ENST00000413026, ENST00000430082, ENST00000453402, ENST00000454759, ENST00000484976, ENST00000494307, ENST00000610256, ENST00000871642, ENST00000871643, ENST00000871644, ENST00000925927, ENST00000925928, ENST00000925929

RefSeq mRNA: 3 — MANE Select: NM_007265 NM_001135752, NM_001135753, NM_007265

CCDS: CCDS44433, CCDS44434, CCDS7321

Canonical transcript exons

ENST00000372979 — 14 exons

Exon	Start	End
ENSE00001102090	73139631	73139737
ENSE00001102096	73136704	73136918
ENSE00001102097	73139309	73139495
ENSE00001102103	73138003	73138070
ENSE00001184758	73154256	73154448
ENSE00001184761	73156275	73156453
ENSE00001184764	73156568	73156655
ENSE00001459242	73163733	73163950
ENSE00001894695	73167866	73168008
ENSE00001924126	73133668	73134813
ENSE00003535292	73152293	73152421
ENSE00003586823	73160434	73160551
ENSE00003643296	73148276	73148404
ENSE00003668605	73146276	73146361

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 91.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9012 / max 654.8865, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110038	23.3012	1815
110039	4.4433	1446
110040	0.1568	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	91.47	gold quality
calcaneal tendon	UBERON:0003701	90.96	gold quality
tendon	UBERON:0000043	90.59	gold quality
islet of Langerhans	UBERON:0000006	88.24	gold quality
ganglionic eminence	UBERON:0004023	87.78	gold quality
tendon of biceps brachii	UBERON:0008188	87.38	silver quality
popliteal artery	UBERON:0002250	87.36	gold quality
tibial artery	UBERON:0007610	87.35	gold quality
adrenal tissue	UBERON:0018303	87.34	gold quality
ventricular zone	UBERON:0003053	87.09	gold quality
cortical plate	UBERON:0005343	86.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.73	gold quality
stromal cell of endometrium	CL:0002255	86.70	gold quality
bone marrow cell	CL:0002092	86.69	gold quality
gall bladder	UBERON:0002110	86.41	gold quality
aorta	UBERON:0000947	86.39	gold quality
medial globus pallidus	UBERON:0002477	86.35	gold quality
monocyte	CL:0000576	86.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.02	gold quality
tonsil	UBERON:0002372	85.98	gold quality
cartilage tissue	UBERON:0002418	85.93	gold quality
mononuclear cell	CL:0000842	85.85	gold quality
leukocyte	CL:0000738	85.81	gold quality
adrenal gland	UBERON:0002369	85.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.51	gold quality
left adrenal gland	UBERON:0001234	85.50	gold quality
ectocervix	UBERON:0012249	85.50	gold quality
rectum	UBERON:0001052	85.48	gold quality
skin of leg	UBERON:0001511	85.48	gold quality
right coronary artery	UBERON:0001625	85.46	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.48

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• Ecd localizes to both nucleus & cytoplasm & shuttles between the nucleus and cytoplasm; however, it exhibits strong nuclear export. Based on previous yeast studies & evidence provided here, we suggest that Ecd functions as a transcriptional regulator. (PMID:19919181)
• Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients. (PMID:22270930)
• Ecd is a novel tumor-promoting factor that is differentially expressed in pancreatic cancer and potentially regulates glucose metabolism within cancer cells. (PMID:22977192)
• TXNIP has a role in the pathway involving hEcd to increase p53 stability and activity (PMID:23880345)
• Ecdysoneless and H-Ras expressing human mammary epithelial cells form tumors in NOD/SCID mice. (PMID:25616580)
• The interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. (PMID:26711270)
• ECD promotes gastric cancer cell invasion and metastasis by preventing E3 ligase ZFP91-mediated hnRNP F ubiquitination and degradation. (PMID:29706618)
• Ecdysoneless Overexpression Drives Mammary Tumorigenesis through Upregulation of C-MYC and Glucose Metabolism. (PMID:35675041)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ecd	ENSDARG00000022944
mus_musculus	Ecd	ENSMUSG00000021810
rattus_norvegicus	Ecd	ENSRNOG00000042253
drosophila_melanogaster	ecd	FBGN0000543
caenorhabditis_elegans		WBGENE00008951

Protein

Protein identifiers

Protein ecdysoneless homolog — O95905 (reviewed: O95905)

Alternative names: Human suppressor of GCR two

All UniProt accessions (5): C9J316, C9JGV1, F2Z2R1, O95905, S4R458

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of p53/TP53 stability and function. Inhibits MDM2-mediated degradation of p53/TP53 possibly by cooperating in part with TXNIP. May be involved transcriptional regulation. In vitro has intrinsic transactivation activity enhanced by EP300. May be a transcriptional activator required for the expression of glycolytic genes. Involved in regulation of cell cycle progression. Proposed to disrupt Rb-E2F binding leading to transcriptional activation of E2F proteins. The cell cycle -regulating function may depend on its RUVBL1-mediated association with the R2TP complex. May play a role in regulation of pre-mRNA splicing. Participates together with DDX39A in mRNA nuclear export.

Subunit / interactions. Interacts with TP53, MDM2, TXNIP. Interacts (phosphorylated) with PIH1D1. Interacts with RUVBL1 mediating the PIH1D1-independent association with the R2TP complex. Interacts with RB1, RBL1 and RBL2; ECD competes with E2F1 for binding to hypophospshorylated RB1. Interacts with EP300. Interacts with DDX39A.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in muscle and heart. Over-expressed in pancreatic and breast cancers.

Post-translational modifications. Phosphorylated predominantly by CK2 on two serine-containing clusters; involved in cell cycle regulation activity.

Similarity. Belongs to the ECD family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95905-1	1	yes
O95905-2	2
O95905-3	3

RefSeq proteins (3): NP_001129224, NP_001129225, NP_009196* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010770	Ecd	Family

Pfam: PF07093

UniProt features (38 total): mutagenesis site 13, region of interest 7, sequence variant 5, compositionally biased region 4, modified residue 3, sequence conflict 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95905-F1	76.46	0.35

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 (3): 503, 505, 518

Mutagenesis-validated functional residues (13):

Position	Phenotype
481	decreases transactivation activity.
484	decreases transactivation activity.
489	decreases transactivation activity.
503	greatly impairs in vitro phosphorylation by ck2 and impairs cell cycle regulation activity; when associated with a-505,
505	greatly impairs in vitro phosphorylation by ck2 and impairs cell cycle regulation activity; when associated with a-503,
510	increases transactivation activity.
512	increases transactivation activity.
518	greatly impairs in vitro phosphorylation by ck2 and impairs cell cycle regulation activity; when associated with a-503,
520	increases transactivation activity.
572	greatly impairs in vitro phosphorylation by ck2 and impairs cell cycle regulation activity; when associated with a-503,
579	greatly impairs in vitro phosphorylation by ck2 and impairs cell cycle regulation activity; when associated with a-503,
584	greatly impairs in vitro phosphorylation by ck2 and impairs cell cycle regulation activity; when associated with a-503,
617	complete loss of interaction with ddx39a.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, BEIER_GLIOMA_STEM_CELL_DN, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_RNA_SPLICING, GOBP_MITOTIC_CELL_CYCLE, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_CELL_CYCLE_PROCESS, GOMF_HISTONE_ACETYLTRANSFERASE_BINDING, GOBP_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II

GO Biological Process (5): mRNA processing (GO:0006397), RNA splicing (GO:0008380), positive regulation of transcription by RNA polymerase II (GO:0045944), fibroblast proliferation (GO:0048144), regulation of G1/S transition of mitotic cell cycle (GO:2000045)

GO Molecular Function (2): histone acetyltransferase binding (GO:0035035), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
mRNA metabolic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cell population proliferation	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECD	AAR2	Q9Y312	672
ECD	LANCL2	Q9NS86	594
ECD	LANCL1	O43813	506
ECD	GMFG	O60234	455
ECD	PIH1D1	Q9NWS0	445
ECD	SUGT1	Q9Y2Z0	444
ECD	ZNHIT2	Q9UHR6	436
ECD	LANCL3	Q6ZV70	419
ECD	HSPA4	P34932	418
ECD	RPS20	P17075	402
ECD	MKRN1	Q9UHC7	370
ECD	ZNHIT6	Q9NWK9	370
ECD	SNRNP200	O75643	364
ECD	Q32Q12	Q32Q12	352
ECD	ACD	Q96AP0	350

IntAct

148 interactions, top by confidence:

A	B	Type	Score
NPHP1	NPHP4	psi-mi:“MI:2364”(proximity)	0.930
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
ECD	PRPF8	psi-mi:“MI:0914”(association)	0.820
ECD	PRPF8	psi-mi:“MI:0915”(physical association)	0.820
SNRNP40	SNRNP200	psi-mi:“MI:0914”(association)	0.810
ECD	PIH1D1	psi-mi:“MI:0915”(physical association)	0.740
PIH1D1	ECD	psi-mi:“MI:0914”(association)	0.740
PIH1D1	ECD	psi-mi:“MI:0915”(physical association)	0.740
PIH1D1	ECD	psi-mi:“MI:0407”(direct interaction)	0.740
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
ECD	TXNIP	psi-mi:“MI:0915”(physical association)	0.690
ECD	RUVBL1	psi-mi:“MI:0915”(physical association)	0.680
RUVBL1	ECD	psi-mi:“MI:0915”(physical association)	0.680
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
PRPF8	PRPF4	psi-mi:“MI:0914”(association)	0.640

BioGRID (214): ECD (Affinity Capture-MS), ECD (Affinity Capture-MS), ECD (Affinity Capture-MS), ECD (Affinity Capture-MS), ECD (Affinity Capture-MS), ECD (Affinity Capture-MS), ECD (Affinity Capture-MS), ECD (Affinity Capture-MS), ECD (Affinity Capture-MS), ECD (Proximity Label-MS), ECD (Proximity Label-MS), ECD (Proximity Label-MS), ECD (Proximity Label-MS), ECD (Proximity Label-MS), ECD (Proximity Label-MS)

ESM2 similar proteins: A0A571BF63, A2BF66, A6QQY4, B0BN28, D3ZWE7, E2QXH7, F6RRD7, O02799, O60566, O70481, O95905, P52630, Q05B18, Q0V7M7, Q13257, Q28IH8, Q2KIY6, Q2TB18, Q3B7T8, Q3U1T9, Q3UB74, Q4R8B9, Q5JTW2, Q5M7C8, Q5PQQ9, Q5RA37, Q5RCY5, Q5SQP1, Q5XGL1, Q5XIZ9, Q6IQY5, Q7T0S7, Q86VD1, Q86VS3, Q86X24, Q8C5W4, Q8CDK3, Q8IWV7, Q8IXW5, Q8N7B1

Diamond homologs: O95905, Q54JR9, Q9CS74, Q9LSM5, Q9W032, Q9US49, Q09307

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 158 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
mRNA Splicing - Minor Pathway	6	13.0×	2e-03
mRNA Splicing - Major Pathway	12	6.4×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	5	20.8×	1e-03
mRNA splicing, via spliceosome	13	8.5×	4e-06
protein stabilization	10	4.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:73156618:C:G	A121P	0.989
10:73148397:C:T	G307E	0.987
10:73160498:C:G	D87H	0.986
10:73156597:A:G	W128R	0.985
10:73156597:A:T	W128R	0.985
10:73134699:A:G	S607P	0.984
10:73163775:A:G	W55R	0.984
10:73163775:A:T	W55R	0.984
10:73134656:A:G	L621P	0.983
10:73134719:A:G	L600P	0.982
10:73139487:A:G	W415R	0.981
10:73139487:A:T	W415R	0.981
10:73160492:A:G	W89R	0.981
10:73160492:A:T	W89R	0.981
10:73156615:C:G	A122P	0.980
10:73139350:G:C	F460L	0.979
10:73139350:G:T	F460L	0.979
10:73139352:A:G	F460L	0.979
10:73156593:A:G	L129P	0.976
10:73152304:C:G	G301R	0.975
10:73154326:C:G	R238P	0.975
10:73148398:C:G	G307R	0.974
10:73148398:C:T	G307R	0.974
10:73152303:C:A	G301V	0.973
10:73134716:A:T	V601D	0.972
10:73139351:A:G	F460S	0.972
10:73134665:G:T	A618D	0.971
10:73152374:A:C	F277L	0.971
10:73152374:A:T	F277L	0.971
10:73152376:A:G	F277L	0.971

dbSNP variants (sampled 300 via entrez): RS1000023644 (10:73146028 G>C), RS1000118910 (10:73157151 G>C), RS1000140418 (10:73147620 T>A), RS1000162490 (10:73166089 C>T), RS1000199532 (10:73138116 C>T), RS1000207628 (10:73143786 T>A,G), RS1000486069 (10:73145798 T>A), RS1000676313 (10:73158176 G>A,C,T), RS1000746477 (10:73159705 G>A), RS1000934102 (10:73139246 A>G), RS1001007309 (10:73158142 G>A), RS1001227323 (10:73164741 G>A,C), RS1001247560 (10:73164739 G>A), RS1001289845 (10:73169562 T>G), RS1001696818 (10:73144566 G>A)

Disease associations

OMIM: gene MIM:616464 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90013466_38	Height	8.000000e-11
GCST90013468_4	Height	9.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	2
Acrolein	increases abundance, affects cotreatment, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression, affects cotreatment	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases expression	1
Caffeine	decreases phosphorylation	1
Dinitrochlorobenzene	affects binding	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tunicamycin	decreases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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