EHD1

Summary

EHD1 (EH domain containing 1, HGNC:3242) is a protein-coding gene on chromosome 11q13.1, encoding EH domain-containing protein 1 (Q9H4M9). ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis.

This gene belongs to a highly conserved gene family encoding EPS15 homology (EH) domain-containing proteins. The protein-binding EH domain was first noted in EPS15, a substrate for the epidermal growth factor receptor. The EH domain has been shown to be an important motif in proteins involved in protein-protein interactions and in intracellular sorting. The protein encoded by this gene is thought to play a role in the endocytosis of IGF1 receptors. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 10938 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited renal tubular disease (Moderate, GenCC)
• Clinical variants (ClinVar): 75 total
• Druggable target: yes
• MANE Select transcript: NM_006795

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3242
Approved symbol	EHD1
Name	EH domain containing 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	H-PAST, HPAST1, FLJ42622, FLJ44618
Ensembl gene	ENSG00000110047
Ensembl biotype	protein_coding
OMIM	605888
Entrez	10938

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000320631, ENST00000359393, ENST00000411683, ENST00000421510, ENST00000433803, ENST00000455148, ENST00000457202, ENST00000466015, ENST00000484846, ENST00000488711, ENST00000489379, ENST00000498472, ENST00000621096, ENST00000909783

RefSeq mRNA: 3 — MANE Select: NM_006795 NM_001282444, NM_001282445, NM_006795

CCDS: CCDS73315, CCDS8084

Canonical transcript exons

ENST00000320631 — 5 exons

Exon	Start	End
ENSE00001063417	64859924	64860336
ENSE00001222092	64878061	64878621
ENSE00001813867	64851642	64854857
ENSE00003668907	64874421	64874518
ENSE00003788678	64855322	64855486

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.8620 / max 2329.1349, expressed in 1820 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120495	60.9842	1818
120493	4.7654	1691
120479	0.8480	75
120478	0.8010	86
120476	0.4534	173
120477	0.2510	47
120496	0.2507	59
120482	0.1973	90
120498	0.1037	37
120500	0.0636	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.65	gold quality
right testis	UBERON:0004534	98.62	gold quality
granulocyte	CL:0000094	97.51	gold quality
blood	UBERON:0000178	97.07	gold quality
testis	UBERON:0000473	96.34	gold quality
spleen	UBERON:0002106	95.80	gold quality
vermiform appendix	UBERON:0001154	95.77	gold quality
apex of heart	UBERON:0002098	95.55	gold quality
right coronary artery	UBERON:0001625	95.45	gold quality
lymph node	UBERON:0000029	95.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.81	gold quality
cerebellar hemisphere	UBERON:0002245	94.79	gold quality
caecum	UBERON:0001153	94.78	gold quality
cerebellar cortex	UBERON:0002129	94.75	gold quality
monocyte	CL:0000576	94.42	gold quality
sperm	CL:0000019	94.36	gold quality
leukocyte	CL:0000738	94.35	gold quality
saphenous vein	UBERON:0007318	94.32	gold quality
cerebellum	UBERON:0002037	94.31	gold quality
bone marrow cell	CL:0002092	94.27	gold quality
mononuclear cell	CL:0000842	94.08	gold quality
periodontal ligament	UBERON:0008266	93.93	gold quality
upper lobe of left lung	UBERON:0008952	93.77	gold quality
male germ cell	CL:0000015	93.67	gold quality
ileal mucosa	UBERON:0000331	93.65	gold quality
popliteal artery	UBERON:0002250	93.55	gold quality
tibial artery	UBERON:0007610	93.53	gold quality
stromal cell of endometrium	CL:0002255	93.51	gold quality
upper lobe of lung	UBERON:0008948	93.41	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.38	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.47
E-MTAB-6379	no	90.18
E-CURD-11	no	42.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, FOXC1, NR4A3, ZNF699

miRNA regulators (miRDB)

48 targeting EHD1, 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-190A-3P	100.00	80.35	5520
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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-2467-3P	98.65	67.18	1969

Literature-anchored findings (GeneRIF, showing 40)

• A tubular EHD1-containing compartment involved in the recycling of major histocompatibility complex class I molecules to the plasma membrane (PMID:12032069)
• EHD3: a protein that resides in recycling tubular and vesicular membrane structures and interacts with EHD1. (PMID:12121420)
• a novel interacting partner for EHD1, rabenosyn-5, was revealed. (PMID:15020713)
• ATP binding is required for oligomerization of mRme-1/EHD1, which in turn is required for its association with endosomes (PMID:15710626)
• Data support a role for EHD1 in beta1 integrin recycling, and demonstrate a requirement for EHD1 in integrin-mediated downstream functions. (PMID:17284518)
• Rab8a and Myosin Vb colocalize to a tubular network containing EHD1 and EHD3, which does not contain Rab11a. (PMID:17507647)
• Solution structure of the 133 C-terminal residues of EHD1, which includes the EH domain, was solved. (PMID:17899392)
• Results show that EHD1 undergoes serine-phosphorylation, and suggest that EHD1 phosphorylation occurs between early endosomes and the endocytic recycling compartment. (PMID:18661112)
• Data show that EH domain mutant (K483E) that associates exclusively with punctate membranes displayed decreased binding to phosphatidylinositol-4-phosphate and other phosphoinositides. (PMID:19369419)
• The results indicate that NPF is the preferred binding motif for the EHD1 EH-domain, but both the DPF and GPF motifs are capable of binding with lower affinity. (PMID:19798736)
• These data implicate MICAL-L1 as an unusual type of Rab effector that regulates endocytic recycling by recruiting and linking EHD1 and Rab8a on membrane tubules. (PMID:19864458)
• A new class of cardiac trafficking proteins(EHD1, EHD2, EHD3, EHD4) regulates cardiac membrane protein targeting. (PMID:20489164)
• EHD1 is involved in the control of CD59 transport from pre-sorting endosomes to the ERC in a PKC-dependent manner (PMID:20961375)
• Rabankyrin-5 interacts with EHD1 and Vps26 to regulate endocytic trafficking and retromer function (PMID:22284051)
• the lipid modifier cPLA2alpha and EHD1 are involved in the vesiculation of CD59-containing endosomes (PMID:22456504)
• evidence that the functions of both EHD1 and EHD4 are primarily in TRE membrane vesiculation, whereas EHD3 is a membrane-tubulating protein. (PMID:24019528)
• MICAL-L1-mediated recruitment of EHD1 to Src-containing recycling endosomes is required for the release of Src from the perinuclear endocytic recycling compartment in response to growth factor stimulation. (PMID:24481818)
• Data indicate that concordant transforming growth factor-beta1 (TGFbeta-1) positive and EH-domain containing 1 (EHD1) negative as a strong favorable prognosis factor in non-small cell lung cancer (NSCLC). (PMID:24946721)
• that Molecule Interacting with CasL Like-1 and Eps15 Homology Domain protein 1 differentially influence microtubule dynamics during early and late mitosis (PMID:25287187)
• Transport through recycling endosomes requires EHD1 recruitment by a phosphatidylserine translocase. (PMID:25595798)
• Authors found that Eps15-homology domain 1 (EHD1), a protein that associates with the endocytic recycling compartment (ERC), colocalizes with active R-Ras in transiently expressed HeLa cells. (PMID:26378252)
• van der Waals interactions should be the main consideration when we design peptide inhibitors of EHD1 EH domain with high affinities. (PMID:26465136)
• Results suggest that EHD1 is a cisplatin (CDDP)-resistant gene that suppresses DNA adduct-induced apoptosis by modulating intracellular CDDP concentrations. (PMID:27411790)
• this study shows that overexpression of EHD1 induced the epithelial-mesenchymal transition and increased the metastatic potential of lung cancer cells in vitro and in vivo (PMID:27531895)
• RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor. (PMID:28215104)
• Depletion of myosin-Va significantly inhibits the attachment of preciliary vesicles to the distal appendages of the mother centriole and decreases cilia assembly. Myosin-Va functions upstream of EHD1- and Rab11-mediated ciliary vesicle formation. (PMID:29335527)
• EHD1 may be an independent prognostic marker in lung cancer and that the NF-kappaB/miR-590/EHD1 signalling pathway might be a potentially effective therapy for overcoming EGFR-TKI resistance. (PMID:29549343)
• PACSIN1 and EHD1 assemble membrane tubules from the developing intracellular cilium that attach to the plasma membrane, creating an extracellular membrane channel to the outside of the cell. (PMID:30683896)
• The expression of EHD1 was negatively correlated with disease-free survival and overall survival of osteosarcoma patients. (PMID:30975166)
• the data obtained in this study suggest that EHD1 plays a critical role in Non-small cell lung cancer (NSCLC) angiogenesis via b2AR signaling and highlight a potential target for antiangiogenic therapy. (PMID:31023336)
• Data support the notion that a pool of centriolar gamma-tubulin and/or alpha-tubulin-beta-tubulin heterodimers anchor MICAL-L1 to the centriole, where it might recruit EHD1 to promote ciliogenesis. (PMID:31615969)
• aberrant EHD1 signaling in the endometrium of RIF patients contributes to impaired decidualization and ultimately to implantation failure. EHD1 interacts with Wnt4, and this interaction leads to the suppression of Wnt4/beta-catenin signaling and impaired decidualization (PMID:31707150)
• RUSC2 and EHD1 function in a common pathway to positively regulate the basal traffic of Epidermal growth factor receptor from the Golgi compartment to the cell surface to ensure optimal surface receptor levels for subsequent ligand-mediated activation and cellular responses. (PMID:31932478)
• EHD1 Modulates Cx43 Gap Junction Remodeling Associated With Cardiac Diseases. (PMID:32138615)
• Identification of phostensin in association with Eps 15 homology domain-containing protein 1 (EHD1) and EHD4. (PMID:32800345)
• Eps15 Homology Domain Protein 4 (EHD4) is required for Eps15 Homology Domain Protein 1 (EHD1)-mediated endosomal recruitment and fission. (PMID:32966336)
• A feedback circuit comprising EHD1 and 14-3-3zeta sustains beta-catenin/c-Myc-mediated aerobic glycolysis and proliferation in non-small cell lung cancer. (PMID:34217785)
• A Founder Mutation in EHD1 Presents with Tubular Proteinuria and Deafness. (PMID:35149593)
• EHD1 promotes the cancer stem cell (CSC)-like traits of glioma cells via interacting with CD44 and suppressing CD44 degradation. (PMID:35616188)
• EHD1 promotes CP110 ubiquitination by centriolar satellite delivery of HERC2 to the mother centriole. (PMID:37074924)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ehd1b	ENSDARG00000014793
danio_rerio	ehd1a	ENSDARG00000098853
mus_musculus	Ehd1	ENSMUSG00000024772
rattus_norvegicus	Ehd1	ENSRNOG00000043503
drosophila_melanogaster	Past1	FBGN0016693
caenorhabditis_elegans		WBGENE00004373

Paralogs (10): EHD3 (ENSG00000013016), EHD2 (ENSG00000024422), EPS15 (ENSG00000085832), EHD4 (ENSG00000103966), EPS15L1 (ENSG00000127527), REPS1 (ENSG00000135597), REPS2 (ENSG00000169891), SRL (ENSG00000185739), ITSN2 (ENSG00000198399), ITSN1 (ENSG00000205726)

Protein

Protein identifiers

EH domain-containing protein 1 — Q9H4M9 (reviewed: Q9H4M9)

Alternative names: PAST homolog 1, Testilin

All UniProt accessions (8): Q9H4M9, A0A024R571, B2R5U3, C9IZH1, C9J2Z4, C9JC03, C9JDQ8, C9JIJ3

UniProt curated annotations — full annotation on UniProt →

Function. ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis. In vitro causes vesiculation of endocytic membranes. Acts in early endocytic membrane fusion and membrane trafficking of recycling endosomes. Recruited to endosomal membranes upon nerve growth factor stimulation, indirectly regulates neurite outgrowth. Plays a role in myoblast fusion. Involved in the unidirectional retrograde dendritic transport of endocytosed BACE1 and in efficient sorting of BACE1 to axons implicating a function in neuronal APP processing. Plays a role in the formation of the ciliary vesicle (CV), an early step in cilium biogenesis. Proposed to be required for the fusion of distal appendage vesicles (DAVs) to form the CV by recruiting SNARE complex component SNAP29. Is required for recruitment of transition zone proteins CEP290, RPGRIP1L, TMEM67 and B9D2, and of IFT20 following DAV reorganization before Rab8-dependent ciliary membrane extension. Required for the loss of CCP110 form the mother centriole essential for the maturation of the basal body during ciliogenesis.

Subunit / interactions. Homooligomer, and heterooligomer with EHD2, EHD3 and EHD4, ATP-binding is required for heterooligomerization. Interacts (via EH domain) with MICALL1 (via NPF1 motif); the interaction is direct and recruits EHD1 to membranes. Interacts with RAB35; the interaction is indirect through MICALL1 and recruits EHD1 to membranes. Interacts (via EH domain) with PACSIN2 (via NPF motifs); regulates localization to tubular recycling endosome membranes. Interacts with PACSIN1. Interacts with RAB8A. Interacts with FER1L5 (via second C2 domain). Interacts with MYOF. Interacts with ZFYVE20. Interacts (via EH domain) with RAB11FIP2. Interacts (via EH domain) with ANKFY1/Rabankyrin-5 (via NPF motif).

Subcellular location. Recycling endosome membrane. Early endosome membrane. Cell membrane. Cell projection. Cilium membrane.

Tissue specificity. Highly expressed in testis.

Domain organisation. The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.

RefSeq proteins (3): NP_001269373, NP_001269374, NP_006786* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000261	EH_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030381	G_DYNAMIN_dom	Domain
IPR031692	EHD_N	Domain
IPR040990	DUF5600	Domain
IPR045063	Dynamin_N	Domain

Pfam: PF00350, PF12763, PF16880, PF18150

UniProt features (44 total): sequence conflict 10, binding site 7, helix 6, mutagenesis site 5, region of interest 5, domain 3, modified residue 3, strand 2, chain 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2JQ6	SOLUTION NMR
2KFF	SOLUTION NMR
2KFG	SOLUTION NMR
2KFH	SOLUTION NMR
2KSP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4M9-F1	89.65	0.74

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (7): 65–72; 220; 258; 489; 491; 493; 500

Post-translational modifications (3): 1, 355, 456

Mutagenesis-validated functional residues (5):

Position	Phenotype
65	abolishes atp-binding and localizes to cytoplasm.
203	greatly reduces oligomerization and interaction with rab11fip2.
468	loss of interaction with micall1.
483	loss of accumulation at the ciliary pocket. loss of function in ciliogenesis. loss of association with tubulovesicular s
485	loss of accumulation at the ciliary pocket. loss of function in ciliogenesis. abolishes interaction with rab11fip2. no e

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 444 (showing top): CREL_01, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_STEROL_HOMEOSTASIS, GCANCTGNY_MYOD_Q6, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, AREB6_03, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, SCIBETTA_KDM5B_TARGETS_UP, GOMF_GTPASE_BINDING

GO Biological Process (18): intracellular protein transport (GO:0006886), endocytosis (GO:0006897), positive regulation of cholesterol storage (GO:0010886), positive regulation of neuron projection development (GO:0010976), neuron projection development (GO:0031175), endocytic recycling (GO:0032456), low-density lipoprotein particle clearance (GO:0034383), cholesterol homeostasis (GO:0042632), protein homooligomerization (GO:0051260), cilium assembly (GO:0060271), protein localization to cilium (GO:0061512), protein localization to plasma membrane (GO:0072659), positive regulation of myoblast fusion (GO:1901741), cellular response to nerve growth factor stimulus (GO:1990090), positive regulation of endocytic recycling (GO:2001137), protein transport (GO:0015031), endosomal transport (GO:0016197), cell projection organization (GO:0030030)

GO Molecular Function (10): calcium ion binding (GO:0005509), ATP binding (GO:0005524), GTP binding (GO:0005525), protein-macromolecule adaptor activity (GO:0030674), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), cadherin binding (GO:0045296), nucleotide binding (GO:0000166), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (20): cytoplasm (GO:0005737), early endosome (GO:0005769), lipid droplet (GO:0005811), plasma membrane (GO:0005886), cilium (GO:0005929), endosome membrane (GO:0010008), membrane (GO:0016020), ciliary pocket membrane (GO:0020018), endocytic vesicle (GO:0030139), platelet dense tubular network membrane (GO:0031095), early endosome membrane (GO:0031901), perinuclear region of cytoplasm (GO:0048471), presynaptic active zone (GO:0048786), recycling endosome membrane (GO:0055038), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), endosome (GO:0005768), endomembrane system (GO:0012505), cell projection (GO:0042995), ciliary membrane (GO:0060170)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
bounding membrane of organelle	3
intracellular protein localization	2
intracellular transport	2
vesicle-mediated transport	2
purine ribonucleoside triphosphate binding	2
protein binding	2
endosome	2
cytoplasmic vesicle	2
endosome membrane	2
protein transport	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
cholesterol storage	1
positive regulation of lipid storage	1
regulation of cholesterol storage	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
neuron development	1
plasma membrane bounded cell projection organization	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
plasma lipoprotein particle clearance	1
low-density lipoprotein particle disassembly	1
sterol homeostasis	1
protein complex oligomerization	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
protein localization to organelle	1
protein localization to membrane	1
protein localization to cell periphery	1
myoblast fusion	1

Protein interactions and networks

STRING

1224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EHD1	MICALL1	Q8N3F8	985
EHD1	SNAP29	O95721	967
EHD1	RBSN	Q9H1K0	960
EHD1	PACSIN2	Q9UNF0	895
EHD1	SNX1	Q13596	813
EHD1	EHBP1	Q8NDI1	800
EHD1	ARF6	P26438	771
EHD1	RAB8A	P24407	770
EHD1	RAB11FIP2	Q7L804	747
EHD1	VPS45	Q9NRW7	746
EHD1	PACSIN1	Q9BY11	728
EHD1	RAB5A	P20339	723
EHD1	RAB11A	P24410	697
EHD1	BIN1	O00499	681
EHD1	EEA1	Q15075	663

IntAct

154 interactions, top by confidence:

A	B	Type	Score
EHD1	MICALL1	psi-mi:“MI:0407”(direct interaction)	0.850
EHD1	MICALL1	psi-mi:“MI:0915”(physical association)	0.850
MICALL1	EHD1	psi-mi:“MI:0915”(physical association)	0.850
EHD1	MICALL1	psi-mi:“MI:0403”(colocalization)	0.850
EHD1	MICALL1	psi-mi:“MI:2364”(proximity)	0.850
RAB11A	EVI5	psi-mi:“MI:0914”(association)	0.800
EHD3	EHD1	psi-mi:“MI:0915”(physical association)	0.760
EHD3	EHD1	psi-mi:“MI:0403”(colocalization)	0.760
EHD1	EHD3	psi-mi:“MI:0915”(physical association)	0.760
EHD1	ANKFY1	psi-mi:“MI:0915”(physical association)	0.730
ANKFY1	EHD1	psi-mi:“MI:0915”(physical association)	0.730
EHD1	RBSN	psi-mi:“MI:0915”(physical association)	0.730
EHD1	RBSN	psi-mi:“MI:0403”(colocalization)	0.730
EXOC8	EXOC5	psi-mi:“MI:0914”(association)	0.730
ANKFY1	EHD1	psi-mi:“MI:0403”(colocalization)	0.730
ANKFY1	EHD1	psi-mi:“MI:0407”(direct interaction)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710

BioGRID (239): EHD1 (Affinity Capture-Western), EHD1 (Two-hybrid), EHD1 (Affinity Capture-MS), RAB11FIP2 (Two-hybrid), RAB11FIP2 (Affinity Capture-Western), RBSN (Two-hybrid), EHD1 (Two-hybrid), EHD3 (Two-hybrid), EHD1 (Two-hybrid), EHD1 (Affinity Capture-MS), EHD1 (Affinity Capture-MS), EHD1 (Affinity Capture-MS), EHD1 (Affinity Capture-MS), EHD1 (Affinity Capture-MS), EHD1 (Affinity Capture-MS)

ESM2 similar proteins: A2VEI2, A8WQT4, B3MIF1, D6WIX5, O70200, P41044, P55008, P55009, P81076, Q02892, Q1LY46, Q21153, Q295E6, Q3UQ44, Q5E9G1, Q5E9R3, Q5RBP4, Q5TM25, Q5ZK33, Q641Z6, Q6AXZ3, Q6CM00, Q6DJ05, Q6FRV0, Q6GQ76, Q74ZK6, Q803R5, Q803V3, Q8CD10, Q8IQ70, Q8IYU8, Q8R491, Q94CF0, Q95PZ2, Q969Q6, Q99P77, Q9BDK2, Q9BZE4, Q9EQP2, Q9FEE2

Diamond homologs: A1CD74, A1CPG1, A1D2B8, A1DC51, A1DDY6, A2QRG2, A2R180, A3LN86, A3M008, A4R8N4, A5DF78, A5DP36, A5DVD6, A5DXI9, A6R7X5, A6RFP4, A6S9N4, A6SIJ6, A7E7N7, A7EKZ0, B0XR88, B0YC95, B2AS96, B2AWS3, L7IIY8, O42287, O54916, O94685, P0CT09, P32521, P42566, P42567, Q0CPW4, Q0D0N9, Q1DQC1, Q1DUU2, Q2H2V8, Q2H922, Q2UCH0, Q2UDY8

SIGNOR signaling

0 interactions.

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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	5	22.7×	2e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	11.0×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
exocytosis	10	13.0×	5e-06
endocytic recycling	5	11.4×	9e-03
endocytosis	11	8.9×	2e-05
protein localization to plasma membrane	9	8.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	6
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

579 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64854853:AGTTC:A	acceptor_gain	1.0000
11:64854854:GTTC:G	acceptor_gain	1.0000
11:64854855:TTC:T	acceptor_gain	1.0000
11:64854856:TC:T	acceptor_gain	1.0000
11:64854857:CCTG:C	acceptor_gain	1.0000
11:64854858:C:CC	acceptor_gain	1.0000
11:64854858:C:CG	acceptor_loss	1.0000
11:64854859:T:G	acceptor_loss	1.0000
11:64854865:C:CT	acceptor_gain	1.0000
11:64854866:G:T	acceptor_gain	1.0000
11:64855316:CCGTA:C	donor_loss	1.0000
11:64855317:CGTAC:C	donor_loss	1.0000
11:64855318:GTAC:G	donor_loss	1.0000
11:64855319:TA:T	donor_loss	1.0000
11:64855484:AACC:A	acceptor_loss	1.0000
11:64855486:CCTGT:C	acceptor_loss	1.0000
11:64855487:CT:C	acceptor_loss	1.0000
11:64855488:T:C	acceptor_loss	1.0000
11:64859962:T:TA	donor_gain	1.0000
11:64872686:A:C	donor_gain	1.0000
11:64874415:GTTTA:G	donor_loss	1.0000
11:64874416:TTTAC:T	donor_loss	1.0000
11:64874417:TTACC:T	donor_loss	1.0000
11:64874418:TAC:T	donor_loss	1.0000
11:64874419:A:C	donor_loss	1.0000
11:64874420:CCT:C	donor_gain	1.0000
11:64878056:GGTAC:G	donor_loss	1.0000
11:64878057:GTAC:G	donor_loss	1.0000
11:64878058:TAC:T	donor_loss	1.0000
11:64878060:C:CT	donor_loss	1.0000

AlphaMissense

3550 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:64854418:A:G	L507P	1.000
11:64854428:C:G	A504P	1.000
11:64854430:A:G	L503P	1.000
11:64854451:A:G	L496P	1.000
11:64854485:A:G	W485R	1.000
11:64854485:A:T	W485R	1.000
11:64854496:A:G	L481P	1.000
11:64854511:A:G	L476P	1.000
11:64854538:G:T	A467D	1.000
11:64854621:C:A	W439C	1.000
11:64854621:C:G	W439C	1.000
11:64854623:A:G	W439R	1.000
11:64854623:A:T	W439R	1.000
11:64855461:A:G	L314P	1.000
11:64859938:C:G	A301P	1.000
11:64859949:A:G	L297P	1.000
11:64859954:A:C	N295K	1.000
11:64859954:A:T	N295K	1.000
11:64859958:A:G	L294P	1.000
11:64860006:A:G	L278P	1.000
11:64860117:C:T	G241D	1.000
11:64860118:C:G	G241R	1.000
11:64860120:A:G	L240P	1.000
11:64860125:C:A	W238C	1.000
11:64860125:C:G	W238C	1.000
11:64860127:A:G	W238R	1.000
11:64860127:A:T	W238R	1.000
11:64860132:A:G	L236P	1.000
11:64860135:G:T	A235D	1.000
11:64860136:C:G	A235P	1.000

dbSNP variants (sampled 300 via entrez): RS1000039155 (11:64862666 A>C,G), RS1000186532 (11:64858601 G>A), RS1000348967 (11:64867028 G>A), RS1000428484 (11:64864024 G>A,C), RS1000457244 (11:64860904 C>G,T), RS1000527583 (11:64853991 C>G,T), RS1000549705 (11:64872442 T>C), RS1000655486 (11:64878572 C>T), RS1000690020 (11:64853272 C>A), RS1001056420 (11:64875509 C>A,T), RS1001106578 (11:64869191 G>A,C,T), RS1001111900 (11:64851818 TTTG>T), RS1001157010 (11:64864395 C>A,T), RS1001203109 (11:64864638 T>C,G), RS1001277383 (11:64877892 G>T)

Disease associations

OMIM: gene MIM:605888 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited renal tubular disease	Moderate	Autosomal recessive

Mondo (1): inherited renal tubular disease (MONDO:0015962)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295942 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 11 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.52	Kd	3000	nM	CHEMBL4215523
5.00	Kd	9900	nM	CHEMBL4214569

PubChem BioAssay actives

2 with measured affinity, of 15 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(3S,6S,9S,15S,18S,21S,24S)-9-[4-[acetyl-[2-(3-hydroxy-6-oxoxanthen-9-yl)benzoyl]amino]butyl]-3-(2-amino-2-oxoethyl)-21-benzyl-18-(2-carboxyethyl)-6-[(4-hydroxyphenyl)methyl]-2,5,8,11,14,17,20,23-octaoxo-1,4,7,10,13,16,19,22-octazabicyclo[22.3.0]heptacosan-15-yl]propanoic acid	1371996: Binding affinity to GST-fused EHD1 EH domain (unknown origin) expressed in Escherichia coli BL21 cells measured after 1 hr in presence of 15 mM NaCl by fluorescence polarization assay	kd	3.0000	uM
3-[(3S,6S,15S,18S,21S,24S)-3-(2-amino-2-oxoethyl)-21-benzyl-18-(2-carboxyethyl)-6-[(4-hydroxyphenyl)methyl]-2,5,8,11,14,17,20,23-octaoxo-1,4,7,10,13,16,19,22-octazabicyclo[22.3.0]heptacosan-15-yl]propanoic acid	1372001: Binding affinity to GST-fused EHD1 EH domain (unknown origin) expressed in Escherichia coli BL21 cells in presence of 150 mM NaCl by isothermal calorimetric titration method	kd	9.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	increases expression, affects expression, affects response to substance, affects cotreatment	3
Valproic Acid	increases methylation, increases expression	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Estradiol	increases expression	2
Formaldehyde	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	decreases expression	1
cobaltous chloride	decreases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	increases oxidation, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4186162	Binding	Inhibition of fluorescence-labelled cNPF1 probe binding to GST-fused EHD1 EH domain (unknown origin) expressed in Escherichia coli BL21 cells pretreated for 30 mins followed by fluorescence-labelled cNPF1 probe addition measured after 1 hr	Thioether-stapled macrocyclic inhibitors of the EH domain of EHD1. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D6TX	TC-71 EHD1 KO	Cancer cell line	Male
CVCL_D6TY	A-673 EHD1 KO	Cancer cell line	Female
CVCL_E0CF	Ubigene HeLa EHD1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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