CUEDC1

Summary

CUEDC1 (CUE domain containing 1, HGNC:31350) is a protein-coding gene on chromosome 17q22, encoding CUE domain-containing protein 1 (Q9NWM3).

Predicted to enable ubiquitin binding activity.

Source: NCBI Gene 404093 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 9 total — 2 pathogenic
• MANE Select transcript: NM_001271875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31350
Approved symbol	CUEDC1
Name	CUE domain containing 1
Location	17q22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180891
Ensembl biotype	protein_coding
OMIM	620552
Entrez	404093

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 27 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000360238, ENST00000407144, ENST00000577422, ENST00000577497, ENST00000577589, ENST00000577830, ENST00000577840, ENST00000578357, ENST00000581391, ENST00000581898, ENST00000582951, ENST00000584746, ENST00000585294, ENST00000878288, ENST00000878289, ENST00000878290, ENST00000878291, ENST00000878292, ENST00000935362, ENST00000935363, ENST00000961306, ENST00000961307, ENST00000961308, ENST00000961309, ENST00000961310, ENST00000961311, ENST00000961312, ENST00000961313, ENST00000961314, ENST00000961315, ENST00000961316, ENST00000961317, ENST00000961318

RefSeq mRNA: 2 — MANE Select: NM_001271875 NM_001271875, NM_001292025

CCDS: CCDS11599

Canonical transcript exons

ENST00000577830 — 11 exons

Exon	Start	End
ENSE00001219849	57871286	57871369
ENSE00001219854	57872663	57872855
ENSE00001219859	57873591	57873717
ENSE00001219884	57885229	57885879
ENSE00001558939	57955225	57955412
ENSE00002685190	57861243	57863285
ENSE00003620559	57879611	57879738
ENSE00003622870	57867357	57867415
ENSE00003661114	57869122	57869193
ENSE00003683814	57868150	57868243
ENSE00003684977	57866474	57866544

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 95.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4891 / max 115.8728, expressed in 1643 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167155	6.2504	1544
167154	2.7191	1408
167156	0.7190	426
167153	0.4790	265
167151	0.1893	60
167157	0.1322	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.56	gold quality
right uterine tube	UBERON:0001302	95.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.22	gold quality
lower esophagus	UBERON:0013473	95.20	gold quality
gastrocnemius	UBERON:0001388	94.70	gold quality
metanephros cortex	UBERON:0010533	94.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.64	gold quality
ventricular zone	UBERON:0003053	94.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.35	gold quality
muscle of leg	UBERON:0001383	94.17	gold quality
mucosa of stomach	UBERON:0001199	94.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.78	gold quality
endocervix	UBERON:0000458	93.62	gold quality
left uterine tube	UBERON:0001303	93.44	gold quality
sural nerve	UBERON:0015488	93.19	gold quality
popliteal artery	UBERON:0002250	93.06	gold quality
tibial artery	UBERON:0007610	93.06	gold quality
right adrenal gland cortex	UBERON:0035827	93.02	gold quality
right coronary artery	UBERON:0001625	92.95	gold quality
left coronary artery	UBERON:0001626	92.90	gold quality
gall bladder	UBERON:0002110	92.90	gold quality
spinal cord	UBERON:0002240	92.88	gold quality
right atrium auricular region	UBERON:0006631	92.61	gold quality
esophagus	UBERON:0001043	92.48	gold quality
coronary artery	UBERON:0001621	92.43	gold quality
right adrenal gland	UBERON:0001233	92.36	gold quality
minor salivary gland	UBERON:0001830	92.33	gold quality
body of stomach	UBERON:0001161	92.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.80

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Data inidicate CUE domain containing 1 (CUEDC1) expression correlates positively with estrogen receptor alpha (ERalpha) in breast cancer, and suggest CUEDC1 is a functional target gene of ERalpha and is required for breast cancer cell proliferation. (PMID:30145202)
• [Prognostic Significance of CUEDC1 in Patients with Acute Myeloid Leukemia (non-M3)]. (PMID:33067938)
• CUEDC1 inhibits epithelial-mesenchymal transition via the TbetaRI/Smad signaling pathway and suppresses tumor progression in non-small cell lung cancer. (PMID:33099540)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cuedc1b	ENSDARG00000054748
danio_rerio	cuedc1a	ENSDARG00000068716
mus_musculus	Cuedc1	ENSMUSG00000018378
rattus_norvegicus	Cuedc1	ENSRNOG00000010257
drosophila_melanogaster	CG12024	FBGN0035283
caenorhabditis_elegans		WBGENE00009649

Protein

Protein identifiers

CUE domain-containing protein 1 — Q9NWM3 (reviewed: Q9NWM3)

All UniProt accessions (5): Q9NWM3, J3KRK6, J3KRV3, J3KT42, J3QLQ8

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NWM3-1	1	yes
Q9NWM3-2	2

RefSeq proteins (2): NP_001258804, NP_001278954 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003892	CUE	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR040192	CUEDC1	Family
IPR040195	CUE_CUED1	Domain

Pfam: PF02845

UniProt features (18 total): region of interest 4, sequence variant 3, helix 3, compositionally biased region 3, chain 1, domain 1, sequence conflict 1, strand 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DHY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWM3-F1	63.33	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): CREL_01, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, AREB6_03, GOZGIT_ESR1_TARGETS_DN, CHANDRAN_METASTASIS_DN, BEIER_GLIOMA_STEM_CELL_DN, TTGCWCAAY_CEBPB_02, NFKB_C, ZIC1_01, NKX25_01, TGGNNNNNNKCCAR_UNKNOWN, RYTTCCTG_ETS2_B, BASAKI_YBX1_TARGETS_DN, HNF1_01

GO Biological Process (0):

GO Molecular Function (2): ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ubiquitin-like protein binding	1
binding	1

Protein interactions and networks

STRING

356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CUEDC1	CUEDC2	Q9H467	530
CUEDC1	CDR2L	Q86X02	507
CUEDC1	CUTC	Q9NTM9	474
CUEDC1	EIF3D	O15371	442
CUEDC1	ASB5	Q8WWX0	411
CUEDC1	DNAJC21	Q5F1R6	403
CUEDC1	ACOT13	Q9NPJ3	392
CUEDC1	LRRC42	Q9Y546	378
CUEDC1	BSDC1	Q9NW68	370
CUEDC1	SGSM2	O43147	357
CUEDC1	TMEM220	Q6QAJ8	351
CUEDC1	HSPH1	Q92598	348
CUEDC1	GBA2	Q9HCG7	338
CUEDC1	TMBIM6	P55061	323
CUEDC1	SBNO2	Q9Y2G9	321

IntAct

124 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
SMURF2	CUEDC1	psi-mi:“MI:0915”(physical association)	0.660
ARRDC1	NEDD4	psi-mi:“MI:0914”(association)	0.640
CUEDC1	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.620
LRRK2	CUEDC1	psi-mi:“MI:0407”(direct interaction)	0.620
	CUEDC1	psi-mi:“MI:0915”(physical association)	0.560
NCK2	CUEDC1	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	CUEDC1	psi-mi:“MI:0915”(physical association)	0.560
SMARCD1	CUEDC1	psi-mi:“MI:0915”(physical association)	0.560
CUEDC1	ABI2	psi-mi:“MI:0915”(physical association)	0.560
UBE2D2	CUEDC1	psi-mi:“MI:0915”(physical association)	0.560
UBE2E2	CUEDC1	psi-mi:“MI:0915”(physical association)	0.560
TMEM51	WWP2	psi-mi:“MI:0914”(association)	0.530
MRPL38	DUSP14	psi-mi:“MI:0914”(association)	0.530
TOM1L2	NDUFA6	psi-mi:“MI:0914”(association)	0.530
NHLH2	AP3B1	psi-mi:“MI:0914”(association)	0.530
LDLRAD4	WWP2	psi-mi:“MI:0914”(association)	0.530
OIP5	CYTH3	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530

BioGRID (125): CUEDC1 (Biochemical Activity), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Biochemical Activity), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS), CUEDC1 (Affinity Capture-MS)

ESM2 similar proteins: A2AFR3, A4FV57, B3KU38, F1LXF1, G3V9M2, O00287, O09112, O88450, P0C6S7, P11274, P22681, P22682, P49797, Q03353, Q03354, Q03355, Q13387, Q14CM0, Q3UR85, Q5RDF5, Q5T6S3, Q68FF6, Q69Z61, Q6GR30, Q6PAJ1, Q6ZMZ0, Q6ZN18, Q6ZWB6, Q7SXV2, Q7Z6G8, Q80ZQ5, Q86VZ6, Q8BIE6, Q8BIZ1, Q8CE64, Q8R3B7, Q8TEK3, Q8WXI2, Q96N64, Q9CXG9

Diamond homologs: Q8R3V6, Q9NWM3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	CUEDC1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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
negative regulation of Notch signaling pathway	5	17.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2429780	NC_000017.10:g.(?55442363)(56309063_?)del	Pathogenic
2429783	NC_000017.10:g.(?55806534)(56540597_?)del	Pathogenic

SpliceAI

2146 predictions. Top by Δscore:

Variant	Effect	Δscore
17:57866469:CTTAC:C	donor_loss	1.0000
17:57866471:TA:T	donor_loss	1.0000
17:57866472:A:C	donor_loss	1.0000
17:57866473:CCT:C	donor_gain	1.0000
17:57866473:CCTCT:C	donor_loss	1.0000
17:57866545:C:CC	acceptor_gain	1.0000
17:57868149:CGA:C	donor_gain	1.0000
17:57868172:T:TA	donor_gain	1.0000
17:57868184:T:TA	donor_gain	1.0000
17:57868244:C:CC	acceptor_gain	1.0000
17:57869120:A:AC	donor_gain	1.0000
17:57869121:C:CC	donor_gain	1.0000
17:57869121:CA:C	donor_gain	1.0000
17:57869126:T:A	donor_gain	1.0000
17:57869300:T:TA	donor_gain	1.0000
17:57869301:C:A	donor_gain	1.0000
17:57871281:GTTAC:G	donor_loss	1.0000
17:57871282:TTAC:T	donor_loss	1.0000
17:57871283:TA:T	donor_loss	1.0000
17:57871284:ACCTG:A	donor_loss	1.0000
17:57871285:C:CG	donor_loss	1.0000
17:57871365:TCGAT:T	acceptor_gain	1.0000
17:57871366:CGAT:C	acceptor_gain	1.0000
17:57871366:CGATC:C	acceptor_gain	1.0000
17:57871367:GAT:G	acceptor_gain	1.0000
17:57871367:GATC:G	acceptor_loss	1.0000
17:57871369:TCTG:T	acceptor_loss	1.0000
17:57871370:C:CC	acceptor_gain	1.0000
17:57871370:CTGGA:C	acceptor_loss	1.0000
17:57872659:CCA:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000046805 (17:57901807 G>A,C,T), RS1000052012 (17:57910893 GCT>G), RS1000054667 (17:57877748 G>A), RS1000055749 (17:57945580 C>G,T), RS1000067619 (17:57938740 G>A), RS1000112498 (17:57904274 A>G), RS1000141383 (17:57902198 AAAAAAACAAAAAAC>A,AAAAAAAC,AAAAAAACAAAAAACAAAAAAC), RS1000157270 (17:57901112 G>A), RS1000160359 (17:57865759 C>T), RS1000167450 (17:57952054 C>T), RS1000185941 (17:57861758 G>A), RS1000200806 (17:57874567 C>T), RS1000245375 (17:57901371 T>A), RS1000272293 (17:57901387 T>C), RS1000317370 (17:57914051 T>C)

Disease associations

OMIM: gene MIM:620552 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000783_3	Multiple sclerosis–Brain Glutamate Levels	2.000000e-06
GCST006073_15	Tenofovir clearance in HIV infection	2.000000e-07
GCST90002395_273	Mean platelet volume	2.000000e-09

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

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
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	3
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, affects expression	2
Benzo(a)pyrene	affects methylation	2
Tetrachlorodibenzodioxin	increases expression	2
Aflatoxin B1	increases methylation	2
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
bisphenol A	increases methylation	1
beta-lapachone	decreases expression	1
afimoxifene	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
ICG 001	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Fulvestrant	increases methylation	1
Atrazine	decreases expression	1
Estrogens	decreases reaction, increases expression	1
Lead	decreases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Quercetin	increases expression	1
Tamoxifen	affects cotreatment, decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders