ENTREP2

Summary

ENTREP2 (endosomal transmembrane epsin interactor 2, HGNC:29075) is a protein-coding gene on chromosome 15q13.1, encoding Protein ENTREP2 (O60320).

Predicted to be located in membrane.

Source: NCBI Gene 23359 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 296 total — 4 pathogenic
• MANE Select transcript: NM_015307

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29075
Approved symbol	ENTREP2
Name	endosomal transmembrane epsin interactor 2
Location	15q13.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0574, TMEM228
Ensembl gene	ENSG00000104059
Ensembl biotype	protein_coding
OMIM	620052
Entrez	23359

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000261275, ENST00000560021, ENST00000560050, ENST00000560082, ENST00000910616, ENST00000918352, ENST00000918353, ENST00000918354, ENST00000918355

RefSeq mRNA: 5 — MANE Select: NM_015307 NM_001387214, NM_001387215, NM_001387216, NM_001387217, NM_015307

CCDS: CCDS45198

Canonical transcript exons

ENST00000261275 — 11 exons

Exon	Start	End
ENSE00000672900	29120252	29123655
ENSE00001784749	29570505	29570979
ENSE00003465657	29252368	29252478
ENSE00003532547	29126267	29126491
ENSE00003533998	29381775	29381831
ENSE00003545805	29137034	29137194
ENSE00003583872	29128789	29128864
ENSE00003588965	29151734	29151841
ENSE00003641870	29124687	29124761
ENSE00003644491	29136366	29136501
ENSE00003789592	29196430	29196564

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 86.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3159 / max 29.1266, expressed in 150 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149069	0.2705	139
149066	0.0455	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.02	gold quality
Ammon’s horn	UBERON:0001954	85.21	gold quality
primary visual cortex	UBERON:0002436	84.68	gold quality
anterior cingulate cortex	UBERON:0009835	84.21	gold quality
temporal lobe	UBERON:0001871	83.97	gold quality
amygdala	UBERON:0001876	83.91	gold quality
superior frontal gyrus	UBERON:0002661	83.12	gold quality
prefrontal cortex	UBERON:0000451	82.63	gold quality
frontal cortex	UBERON:0001870	82.49	gold quality
cerebral cortex	UBERON:0000956	82.40	gold quality
right frontal lobe	UBERON:0002810	82.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.62	gold quality
putamen	UBERON:0001874	79.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.59	gold quality
caudate nucleus	UBERON:0001873	78.15	gold quality
cortical plate	UBERON:0005343	77.32	gold quality
nucleus accumbens	UBERON:0001882	77.08	gold quality
brain	UBERON:0000955	76.10	gold quality
hypothalamus	UBERON:0001898	74.56	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.21	gold quality
cerebellum	UBERON:0002037	73.49	gold quality
cerebellar cortex	UBERON:0002129	73.41	gold quality
cerebellar hemisphere	UBERON:0002245	73.39	gold quality
mucosa of transverse colon	UBERON:0004991	72.82	gold quality
body of pancreas	UBERON:0001150	72.06	gold quality
pancreas	UBERON:0001264	71.55	gold quality
islet of Langerhans	UBERON:0000006	70.11	gold quality
substantia nigra	UBERON:0002038	69.85	gold quality
transverse colon	UBERON:0001157	68.32	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	19.40
E-ANND-3	no	0.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting ENTREP2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam189a1	ENSDARG00000053380
mus_musculus	Entrep2	ENSMUSG00000030518
rattus_norvegicus	Entrep2	ENSRNOG00000023496

Paralogs (2): ENTREP1 (ENSG00000135063), ENTREP3 (ENSG00000160767)

Protein

Protein identifiers

Protein ENTREP2 — O60320 (reviewed: O60320)

Alternative names: Endosomal transmembrane epsin interactor 2, Transmembrane protein 228

All UniProt accessions (2): H0YKM1, O60320

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the ENTREP family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60320-1	1	yes
O60320-2	2

RefSeq proteins (5): NP_001374143, NP_001374144, NP_001374145, NP_001374146, NP_056122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030431	ENTREP1-3	Family

Pfam: PF04103

UniProt features (15 total): sequence variant 5, transmembrane region 4, compositionally biased region 3, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60320-F1	59.09	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): chr15q13, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, BASAKI_YBX1_TARGETS_DN, MODULE_207, BMI1_DN_MEL18_DN.V1_UP, CBX7_TARGET_GENES, HSD17B8_TARGET_GENES, IGLV5_37_TARGET_GENES, LHX9_TARGET_GENES, MIR570_3P, MIR106B_5P, MIR20A_5P, MIR106A_5P, MIR17_5P, MIR20B_5P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENTREP2	DRC11L	A6NCM1	606
ENTREP2	TMEM278	A6NKF7	452
ENTREP2	TMEM145	Q8NBT3	450
ENTREP2	APBA2	Q99767	450
ENTREP2	STUM	Q69YW2	447
ENTREP2	FAM81A	Q8TBF8	432
ENTREP2	FAM171B	Q6P995	430
ENTREP2	HEATR9	A2RTY3	428
ENTREP2	ANKRD62	A6NC57	420
ENTREP2	TMEM179	Q6ZVK1	420
ENTREP2	CT62	P0C5K7	418
ENTREP2	RNF212	Q495C1	407
ENTREP2	TMEM91	Q6ZNR0	405
ENTREP2	N4BP1	O75113	392
ENTREP2	AMER3	Q8N944	392

IntAct

0 interactions, top by confidence:

BioGRID (1): FAM189A1 (Biochemical Activity)

ESM2 similar proteins: A0A1B0GW64, A0A5F4BST2, A0PJX4, A8MVS5, A8MWV9, B0FP48, E5RIL1, E9PGG2, O14836, O60320, O95998, P09564, Q01113, Q01114, Q13477, Q2KI80, Q2T9R2, Q3TS39, Q3UPR0, Q3URD2, Q4V9L6, Q5FVJ4, Q5M869, Q6A044, Q6UWJ8, Q75VT8, Q864V4, Q8BRJ3, Q8BX43, Q8C503, Q8IVY1, Q8K5A9, Q8N112, Q8NC24, Q8NDY8, Q8QZT4, Q8R138, Q969Z4, Q9BUF7, Q9CQM1

Diamond homologs: O60320, P81408, Q15884, Q4FZH1, Q5HZJ5, Q6A044

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	177
Likely benign	99
Benign	6

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
146702	GRCh38/hg38 15q11.2-14(chr15:23319714-38089582)x1	Pathogenic
1703672	GRCh37/hg19 15q11.2-13.1(chr15:22770421-29855014)	Pathogenic
267796	NM_138704.4(NSMCE3):c.626C>T (p.Pro209Leu)	Pathogenic
57008	GRCh38/hg38 15q13.1-13.3(chr15:28314197-32343758)x1	Pathogenic

SpliceAI

5304 predictions. Top by Δscore:

Variant	Effect	Δscore
15:29126492:C:CC	acceptor_gain	1.0000
15:29128783:GCTTA:G	donor_loss	1.0000
15:29128784:CTTAC:C	donor_loss	1.0000
15:29128785:TTA:T	donor_loss	1.0000
15:29128786:TA:T	donor_loss	1.0000
15:29128788:C:CT	donor_loss	1.0000
15:29181894:T:A	donor_gain	1.0000
15:29252362:ACTT:A	donor_loss	1.0000
15:29252363:CTTA:C	donor_loss	1.0000
15:29252364:TTACC:T	donor_loss	1.0000
15:29252366:A:AC	donor_gain	1.0000
15:29252366:A:C	donor_loss	1.0000
15:29252367:C:A	donor_loss	1.0000
15:29252367:C:CC	donor_gain	1.0000
15:29252367:CCAA:C	donor_gain	1.0000
15:29381828:GCACC:G	acceptor_loss	1.0000
15:29381829:CACCT:C	acceptor_loss	1.0000
15:29381830:ACC:A	acceptor_loss	1.0000
15:29381832:C:CA	acceptor_loss	1.0000
15:29381833:T:A	acceptor_loss	1.0000
15:29124124:AGTGC:A	donor_gain	0.9900
15:29124211:CAGG:C	donor_gain	0.9900
15:29124235:C:A	donor_gain	0.9900
15:29124306:G:A	donor_gain	0.9900
15:29126262:CCTA:C	donor_loss	0.9900
15:29126264:TA:T	donor_loss	0.9900
15:29126487:TGGTA:T	acceptor_gain	0.9900
15:29126488:GGTA:G	acceptor_gain	0.9900
15:29126489:GTA:G	acceptor_gain	0.9900
15:29126490:TA:T	acceptor_gain	0.9900

AlphaMissense

3467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:29381809:C:T	G81D	1.000
15:29381810:C:G	G81R	1.000
15:29381818:C:T	G78E	1.000
15:29381819:C:G	G78R	1.000
15:29381819:C:T	G78R	1.000
15:29570519:A:G	W69R	1.000
15:29570519:A:T	W69R	1.000
15:29570574:G:C	S50R	1.000
15:29570574:G:T	S50R	1.000
15:29570576:T:G	S50R	1.000
15:29570596:C:T	G43E	1.000
15:29570597:C:G	G43R	1.000
15:29570597:C:T	G43R	1.000
15:29570618:C:G	G36R	1.000
15:29570618:C:T	G36R	1.000
15:29151793:A:G	C191R	0.999
15:29151837:A:G	L176P	0.999
15:29252426:C:T	G110D	0.999
15:29252427:C:G	G110R	0.999
15:29252438:A:G	L106P	0.999
15:29252441:A:C	M105R	0.999
15:29252467:G:C	F96L	0.999
15:29252467:G:T	F96L	0.999
15:29252469:A:G	F96L	0.999
15:29381812:A:T	I80K	0.999
15:29381818:C:A	G78V	0.999
15:29570512:C:T	G71D	0.999
15:29570513:C:A	G71C	0.999
15:29570513:C:G	G71R	0.999
15:29570517:C:A	W69C	0.999

dbSNP variants (sampled 300 via entrez): RS1000002397 (15:29281116 A>G), RS1000013013 (15:29182839 TA>T,TAA), RS1000013917 (15:29204842 C>T), RS1000016408 (15:29605521 A>G), RS1000019211 (15:29340013 T>C), RS1000019706 (15:29479660 C>A,T), RS1000019786 (15:29628485 A>C), RS1000020193 (15:29657226 T>C,G), RS1000020535 (15:29590134 G>A), RS1000025846 (15:29602935 G>A,T), RS1000030350 (15:29325860 A>T), RS1000031950 (15:29518300 A>G,T), RS1000039286 (15:29241059 G>A), RS1000043193 (15:29322464 T>C), RS1000044413 (15:29162774 C>T)

Disease associations

OMIM: gene MIM:620052 | disease phenotypes: MIM:617241, MIM:105830

GenCC curated gene-disease

Mondo (3): lung disease, immunodeficiency, and chromosome breakage syndrome; (MONDO:0014984), Angelman syndrome (MONDO:0007113), congenital portosystemic shunt (MONDO:0018811)

Orphanet (2): Angelman syndrome (Orphanet:72), Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001376_1	Life threatening arrhythmia	5.000000e-06
GCST001762_795	Obesity-related traits	7.000000e-06
GCST008516_7	Skin pigmentation (conditioned on rs1426654 and rs35397)	6.000000e-10
GCST009507_5	Triglyceride levels	2.000000e-07
GCST012048_33	Triglyceride levels	2.000000e-09
GCST012490_490	Femur bone mineral density x serum urate levels interaction	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004269	cardiac arrhythmia
EFO:0004530	triglyceride measurement
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D017204	Angelman Syndrome	C10.228.662.075; C16.131.077.095; C16.131.260.040; C16.320.180.040; C16.320.447.250
C531619	Happy puppet syndrome (formerly) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	2
Valproic Acid	affects expression, increases methylation	2
trichostatin A	decreases expression	1
sodium arsenite	affects methylation	1
pentanal	increases expression	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02893254	PHASE3	COMPLETED	Efficacy and Safety of IBI303 in Adult Patients With Active Ankylosing Spondylitis
NCT03882918	PHASE3	TERMINATED	An Open-Label Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of OV101 in Individuals With Angelman Syndrome
NCT06415344	PHASE3	ENROLLING_BY_INVITATION	Long-term Extension of GTX-102 in Angelman Syndrome
NCT06617429	PHASE3	ACTIVE_NOT_RECRUITING	Phase 3 Efficacy and Safety Study of GTX-102 in Pediatric Subjects With Angelman Syndrome (AS)
NCT06914609	PHASE3	RECRUITING	REVEAL: A Phase 3 Study of ION582 in Angelman Syndrome
NCT07605429	PHASE3	NOT_YET_RECRUITING	Phase III Clinical Study of Rugonersen in Angelman Syndrome.
NCT02056665	PHASE2	COMPLETED	Study to Evaluate the Efficacy and Safety of Minocycline in Angelman Syndrome
NCT02996305	PHASE2	COMPLETED	A Study in Adults and Adolescents With Angelman Syndrome (STARS)
NCT05011851	PHASE2	COMPLETED	An Open-Label Study of the Safety, Tolerability, and Pharmacokinetics of Oral NNZ-2591 in Angelman Syndrome
NCT05630066	PHASE2	COMPLETED	A Study to Investigate the Pharmacokinetics (PK) and Safety and to Provide Proof of Mechanism of Alogabat in Children and Adolescents Aged 5-17 Years With Angelman Syndrome (AS) With Deletion Genotype.
NCT07157254	PHASE2	RECRUITING	A Safety and Efficacy Study of GTX-102 in Subjects With Deletion- or Nondeletion-type Angelman Syndrome (AS)
NCT00829439	PHASE1	COMPLETED	Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome
NCT03109756	PHASE1	COMPLETED	Single Dose Pharmacokinetic (PK) Study
NCT04428281	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of RO7248824 in Participants With Angelman Syndrome (AS)
NCT04863794	PHASE1	COMPLETED	A Study To Assess Distribution Of RO7248824 In The Central Nervous System Following Single Intrathecal Doses Of [89zr] Labeled RO7248824 In Healthy Male Participants
NCT01281475	PHASE2/PHASE3	COMPLETED	A Trial of Levodopa in Angelman Syndrome
NCT04259281	PHASE1/PHASE2	COMPLETED	A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome
NCT05127226	PHASE1/PHASE2	RECRUITING	HALOS: A Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of Multiple Ascending Doses of ION582 in Participants With Angelman Syndrome
NCT07181837	PHASE1/PHASE2	RECRUITING	A Phase 1/2 Study of the Safety and Efficacy of MVX-220 in Angelman Syndrome
NCT04103333	EARLY_PHASE1	COMPLETED	Angelman Syndrome (AS) Biomarker Study
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00296764	Not specified	COMPLETED	Characterization of Angelman Syndrome
NCT00348933	Not specified	COMPLETED	Dietary Supplements for the Treatment of Angelman Syndrome
NCT01531582	Not specified	COMPLETED	Minocycline in the Treatment of Angelman Syndrome
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT02670694	Not specified	COMPLETED	Sleep Abnormalities in Rare Genetic Disorders: AS, RTT, and PW
NCT03235037	Not specified	COMPLETED	Clinical Trial of Levodopa/Carbidopa ( Sinemet) Therapy in Angel Man Syndrome
NCT03358823	Not specified	COMPLETED	Study on the Brain Network of Angelman Syndrome
NCT03644693	Not specified	COMPLETED	Nutritional Formulation for Angelman Syndrome
NCT03650569	Not specified	COMPLETED	Italian Angelman Syndrome Registry
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03836300	Not specified	ENROLLING_BY_INVITATION	Parent and Infant Inter(X)Action Intervention (PIXI)
NCT04392596	Not specified	COMPLETED	Study of Bone Mineral Density and Trabecular Bone Score in Patients With Ankylosing Spondylitis
NCT04507997	Not specified	RECRUITING	Angelman Syndrome Natural History Study
NCT04768803	Not specified	UNKNOWN	Ghrelin in Patients With a Rare Disease Associated With Intellectual Disability, and Hyperphagia, and/or Overweight, and/or Obesity
NCT05100810	Not specified	UNKNOWN	Angelman Syndrome Natural History Study-FAST UK
NCT05293184	Not specified	RECRUITING	The Global Angelman Syndrome Registry
NCT05637697	Not specified	COMPLETED	Angelman Syndrome Video Assessment (ASVA) Source Material Study
NCT05783791	Not specified	COMPLETED	Development of a Newborn Screening Assay for Angelman Syndrome and Prader-Willi Syndrome
NCT05945576	Not specified	RECRUITING	IDMet (RaDiCo Cohort) (RaDiCo-IDMet)