ENTHD1

Summary

ENTHD1 (ENTH domain containing 1, HGNC:26352) is a protein-coding gene on chromosome 22q13.1, encoding ENTH domain-containing protein 1 (Q8IYW4).

Predicted to enable clathrin binding activity and phospholipid binding activity. Predicted to be involved in endocytosis. Predicted to be part of clathrin vesicle coat. Predicted to be active in endosome and plasma membrane.

Source: NCBI Gene 150350 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_152512

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26352
Approved symbol	ENTHD1
Name	ENTH domain containing 1
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25421
Ensembl gene	ENSG00000176177
Ensembl biotype	protein_coding
Entrez	150350

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000325157, ENST00000490326

RefSeq mRNA: 1 — MANE Select: NM_152512 NM_152512

CCDS: CCDS13998

Canonical transcript exons

ENST00000325157 — 7 exons

Exon	Start	End
ENSE00001247423	39765223	39765609
ENSE00001247429	39820993	39821113
ENSE00001247443	39743044	39744283
ENSE00001247451	39835840	39835958
ENSE00001290271	39887400	39887903
ENSE00001325790	39861765	39862007
ENSE00001425670	39893695	39893760

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 88.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0113 / max 8.5706, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194298	0.0096	4
194297	0.0017	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.31	gold quality
right testis	UBERON:0004534	74.18	gold quality
left testis	UBERON:0004533	73.14	gold quality
testis	UBERON:0000473	72.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.05	gold quality
tibial nerve	UBERON:0001323	64.88	gold quality
sperm	CL:0000019	61.68	silver quality
lower lobe of lung	UBERON:0008949	55.40	silver quality
lymph node	UBERON:0000029	54.41	gold quality
adult organism	UBERON:0007023	52.61	gold quality
vermiform appendix	UBERON:0001154	52.24	gold quality
nucleus accumbens	UBERON:0001882	52.24	gold quality
monocyte	CL:0000576	50.20	gold quality
caecum	UBERON:0001153	49.52	gold quality
leukocyte	CL:0000738	49.01	silver quality
granulocyte	CL:0000094	44.91	silver quality
gall bladder	UBERON:0002110	44.18	silver quality
tonsil	UBERON:0002372	43.53	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
colonic epithelium	UBERON:0000397	42.30	gold quality
visceral pleura	UBERON:0002401	42.29	gold quality
vastus lateralis	UBERON:0001379	41.67	gold quality
oviduct epithelium	UBERON:0004804	41.67	gold quality
quadriceps femoris	UBERON:0001377	41.63	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
islet of Langerhans	UBERON:0000006	41.17	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting ENTHD1, 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-4776-3P	100.00	68.73	1340
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-6830-5P	99.01	68.73	1884

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Enthd1	ENSMUSG00000050439
rattus_norvegicus	Enthd1	ENSRNOG00000025344
drosophila_melanogaster	lqf	FBGN0028582
caenorhabditis_elegans		WBGENE00001329

Paralogs (5): EPN3 (ENSG00000049283), EPN1 (ENSG00000063245), EPN2 (ENSG00000072134), CLINT1 (ENSG00000113282), MYCBPAP (ENSG00000136449)

Protein

Protein identifiers

ENTH domain-containing protein 1 — Q8IYW4 (reviewed: Q8IYW4)

Alternative names: Epsin-2B

All UniProt accessions (1): Q8IYW4

RefSeq proteins (1): NP_689725* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008942	ENTH_VHS	Homologous_superfamily
IPR013809	ENTH	Domain

Pfam: PF01417

UniProt features (4 total): chain 1, domain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYW4-F1	57.58	0.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): RNGTGGGC_UNKNOWN, GOBP_VESICLE_MEDIATED_TRANSPORT, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOCC_COATED_VESICLE, TCF11_01, GGGNNTTTCC_NFKB_Q6_01, GOCC_VESICLE_COAT, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS, NKX3A_01, GOCC_CLATHRIN_COATED_VESICLE, GOCC_CLATHRIN_COAT, GOCC_CLATHRIN_VESICLE_COAT, chr22q13, GOCC_CLATHRIN_COATED_VESICLE_MEMBRANE

GO Biological Process (1): endocytosis (GO:0006897)

GO Molecular Function (3): phospholipid binding (GO:0005543), clathrin binding (GO:0030276), protein binding (GO:0005515)

GO Cellular Component (4): endosome (GO:0005768), plasma membrane (GO:0005886), clathrin vesicle coat (GO:0030125), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
lipid binding	1
protein binding	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
clathrin coat	1
vesicle coat	1
clathrin-coated vesicle membrane	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

657 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENTHD1	S4R434	S4R434	575
ENTHD1	ZNHIT2	Q9UHR6	531
ENTHD1	KATNA1	O75449	520
ENTHD1	PRDM10	Q9NQV6	496
ENTHD1	TSGA10IP	Q3SY00	473
ENTHD1	SLITRK1	Q96PX8	462
ENTHD1	KIF18A	Q8NI77	458
ENTHD1	FAXC	Q5TGI0	454
ENTHD1	HERC5	Q9UII4	450
ENTHD1	LINC03042	Q6ZUL3	431
ENTHD1	FSCN3	Q9NQT6	427
ENTHD1	MEIOB	Q8N635	408
ENTHD1	CNPY2	Q9Y2B0	402
ENTHD1	HUS1B	Q8NHY5	378
ENTHD1	DNAJC11	Q9NVH1	373

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ENTHD1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.670
SNAPIN	ENTHD1	psi-mi:“MI:0915”(physical association)	0.670
ENTHD1	HADHA	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350
ENTHD1	C1orf226	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): ENTHD1 (Two-hybrid), ENTHD1 (Proximity Label-MS), SNAPIN (Affinity Capture-MS), TRIOBP (Affinity Capture-MS), LRRC45 (Affinity Capture-MS), SASS6 (Affinity Capture-MS), KLC4 (Affinity Capture-MS), C1orf226 (Affinity Capture-MS), VPS53 (Affinity Capture-MS), SMTNL2 (Affinity Capture-MS), TXLNG (Affinity Capture-MS), CEP250 (Affinity Capture-MS), TXLNA (Affinity Capture-MS), CEP55 (Affinity Capture-MS), BLOC1S3 (Affinity Capture-MS)

ESM2 similar proteins: B0S6S9, B7ZUL2, D2HXI8, D3Z987, D3ZJ47, E1BC15, E1BFR5, O43303, P10242, P29352, P51957, P56715, Q06190, Q06BR1, Q0P5X5, Q1X8D7, Q3V089, Q49A88, Q5BQN8, Q5RCM2, Q5RD97, Q5SW75, Q5W0B1, Q5ZLE9, Q60DG4, Q62394, Q6KAQ7, Q6NRK3, Q6PJP8, Q6ZP01, Q6ZU52, Q6ZV73, Q76I76, Q80WQ8, Q86UW6, Q86V20, Q86XD8, Q8C0P0, Q8IYH5, Q8IYW4

Diamond homologs: A7Z035, O74423, O88339, O95208, P47160, P78813, Q05785, Q12518, Q14677, Q4V882, Q54EH1, Q67YI9, Q80VP1, Q8CHU3, Q8IYW4, Q8VY07, Q91W69, Q93YP4, Q99KN9, Q9H201, Q9Y6I3, Q9Z1Z3, Q07872

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	18
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2007 predictions. Top by Δscore:

Variant	Effect	Δscore
22:39821111:GTCC:G	acceptor_loss	1.0000
22:39821114:C:A	acceptor_loss	1.0000
22:39861804:T:TA	donor_gain	1.0000
22:39876444:T:TA	donor_gain	1.0000
22:39893689:TGTTA:T	donor_loss	1.0000
22:39893690:GTTAC:G	donor_loss	1.0000
22:39893691:TTACC:T	donor_loss	1.0000
22:39893692:TACC:T	donor_loss	1.0000
22:39893694:C:CA	donor_loss	1.0000
22:39744238:A:C	acceptor_gain	0.9900
22:39744284:C:CC	acceptor_gain	0.9900
22:39782967:T:TC	acceptor_gain	0.9900
22:39820988:TTTAC:T	donor_loss	0.9900
22:39820989:TTAC:T	donor_loss	0.9900
22:39820990:TAC:T	donor_loss	0.9900
22:39820991:ACC:A	donor_loss	0.9900
22:39820992:C:CG	donor_loss	0.9900
22:39820992:CCT:C	donor_gain	0.9900
22:39820994:TGC:T	donor_gain	0.9900
22:39821016:T:TA	donor_gain	0.9900
22:39821114:C:CC	acceptor_gain	0.9900
22:39821118:C:CT	acceptor_gain	0.9900
22:39821119:A:T	acceptor_gain	0.9900
22:39835833:GACTT:G	donor_loss	0.9900
22:39835834:ACTTA:A	donor_loss	0.9900
22:39835835:CTTA:C	donor_loss	0.9900
22:39835836:TTA:T	donor_loss	0.9900
22:39835837:TACC:T	donor_loss	0.9900
22:39835838:A:AT	donor_loss	0.9900
22:39861763:A:AC	donor_gain	0.9900

AlphaMissense

3998 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:39887679:C:G	A24P	0.998
22:39887495:C:T	G85E	0.997
22:39887507:A:G	L81P	0.997
22:39887530:T:A	K73N	0.997
22:39887530:T:G	K73N	0.997
22:39887531:T:A	K73I	0.997
22:39887519:A:G	L77P	0.996
22:39887525:A:G	L75P	0.996
22:39887547:A:G	W68R	0.996
22:39887547:A:T	W68R	0.996
22:39887532:T:C	K73E	0.995
22:39861995:C:G	R121P	0.994
22:39887495:C:A	G85V	0.994
22:39887500:C:A	K83N	0.994
22:39887500:C:G	K83N	0.994
22:39887545:C:A	W68C	0.994
22:39887545:C:G	W68C	0.994
22:39887683:C:A	R22S	0.994
22:39887683:C:G	R22S	0.994
22:39887431:A:C	F106L	0.993
22:39887431:A:T	F106L	0.993
22:39887433:A:G	F106L	0.993
22:39887507:A:T	L81H	0.993
22:39887544:G:T	R69S	0.993
22:39887569:T:A	R60S	0.993
22:39887569:T:G	R60S	0.993
22:39887687:A:T	V21D	0.993
22:39887673:A:G	S26P	0.992
22:39887525:A:T	L75H	0.990
22:39887529:A:G	S74P	0.990

dbSNP variants (sampled 300 via entrez): RS1000028149 (22:39758149 G>A), RS1000028201 (22:39855308 C>G), RS1000041339 (22:39750637 T>G), RS1000055651 (22:39847940 G>A), RS1000068936 (22:39859763 A>C), RS1000102681 (22:39756487 C>A), RS1000134048 (22:39857688 T>C), RS1000171593 (22:39755626 C>T), RS1000185422 (22:39854995 A>G), RS1000190568 (22:39800049 T>C), RS1000199757 (22:39852696 A>G), RS1000230604 (22:39814060 A>G), RS1000256161 (22:39862210 G>A), RS1000258677 (22:39815357 C>A,G,T), RS1000298017 (22:39793838 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005752_107	Systemic lupus erythematosus	5.000000e-08
GCST005951_24	Body mass index	2.000000e-08
GCST009391_1758	Metabolite levels	1.000000e-06
GCST009597_201	Multiple sclerosis	1.000000e-08
GCST009600_9	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	7.000000e-11
GCST90002382_511	Eosinophil percentage of white cells	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010370	lysophosphatidylethanolamine 20:4 measurement
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	decreases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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