EHBP1L1

Summary

EHBP1L1 (EH domain binding protein 1 like 1, HGNC:30682) is a protein-coding gene on chromosome 11q13.1, encoding EH domain-binding protein 1-like protein 1 (Q8N3D4). May act as Rab effector protein and play a role in vesicle trafficking.

Predicted to act upstream of or within several processes, including enucleation; erythrocyte differentiation; and mitochondrion localization. Located in membrane.

Source: NCBI Gene 254102 — RefSeq curated summary.

At a glance

• Gene–disease (curated): non-immune hydrops fetalis (Strong, GenCC)
• GWAS associations: 20
• Clinical variants (ClinVar): 297 total — 1 likely-pathogenic
• MANE Select transcript: NM_001099409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30682
Approved symbol	EHBP1L1
Name	EH domain binding protein 1 like 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp762C186, TANGERIN
Ensembl gene	ENSG00000173442
Ensembl biotype	protein_coding
OMIM	619583
Entrez	254102

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 24 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000309295, ENST00000526990, ENST00000527214, ENST00000529056, ENST00000529099, ENST00000529596, ENST00000531106, ENST00000533237, ENST00000533364, ENST00000533465, ENST00000634639, ENST00000905137, ENST00000939748, ENST00000968317, ENST00000968318, ENST00000968319, ENST00000968320, ENST00000968321, ENST00000968322, ENST00000968323, ENST00000968324, ENST00000968325, ENST00000968326, ENST00000968327, ENST00000968328, ENST00000968329, ENST00000968330, ENST00000968331, ENST00000968332, ENST00000968333, ENST00000968334

RefSeq mRNA: 2 — MANE Select: NM_001099409 NM_001099409, NM_001351087

CCDS: CCDS44649

Canonical transcript exons

ENST00000309295 — 19 exons

Exon	Start	End
ENSE00001191785	65591976	65592090
ENSE00001191789	65591800	65591873
ENSE00001191793	65590493	65590592
ENSE00001191803	65590087	65590210
ENSE00001191808	65589936	65589991
ENSE00001191824	65584959	65585591
ENSE00001191846	65581539	65583765
ENSE00001191850	65581211	65581373
ENSE00001191857	65581058	65581126
ENSE00001191865	65580337	65580479
ENSE00001191873	65580081	65580259
ENSE00001254921	65579341	65579436
ENSE00001254955	65589751	65589820
ENSE00001254973	65584241	65584398
ENSE00001422458	65592203	65592650
ENSE00001562334	65576053	65576406
ENSE00002517570	65579936	65579989
ENSE00003543554	65579078	65579135
ENSE00003657689	65584486	65584534

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.0070 / max 441.3411, expressed in 1683 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115176	28.9625	1682
115177	0.0445	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.02	gold quality
lower esophagus	UBERON:0013473	98.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.65	gold quality
right coronary artery	UBERON:0001625	98.60	gold quality
monocyte	CL:0000576	98.35	gold quality
mucosa of stomach	UBERON:0001199	98.32	gold quality
ascending aorta	UBERON:0001496	98.29	gold quality
thoracic aorta	UBERON:0001515	98.28	gold quality
gastrocnemius	UBERON:0001388	98.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.22	gold quality
popliteal artery	UBERON:0002250	98.21	gold quality
tibial artery	UBERON:0007610	98.21	gold quality
mononuclear cell	CL:0000842	98.16	gold quality
aorta	UBERON:0000947	98.15	gold quality
descending thoracic aorta	UBERON:0002345	98.12	gold quality
left uterine tube	UBERON:0001303	97.98	gold quality
left coronary artery	UBERON:0001626	97.93	gold quality
leukocyte	CL:0000738	97.92	gold quality
lower esophagus mucosa	UBERON:0035834	97.92	gold quality
body of uterus	UBERON:0009853	97.85	gold quality
muscle of leg	UBERON:0001383	97.80	gold quality
spleen	UBERON:0002106	97.46	gold quality
apex of heart	UBERON:0002098	97.45	gold quality
coronary artery	UBERON:0001621	97.12	gold quality
esophagus	UBERON:0001043	97.06	gold quality
colonic epithelium	UBERON:0000397	96.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.87	gold quality
ectocervix	UBERON:0012249	96.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting EHBP1L1, 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-4531	99.99	69.70	3181
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334

Literature-anchored findings (GeneRIF, showing 2)

• Data demonstrate that EHBP1L1 links Rab8 and the Bin1-dynamin complex, which generates membrane curvature and excises the vesicle at the endocytic recycling compartment for apical transport. (PMID:26833786)
• EHBP1L1 Drives Immune Evasion in Renal Cell Carcinoma through Binding and Stabilizing JAK1. (PMID:36775874)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ehbp1l1a	ENSDARG00000057353
mus_musculus	Ehbp1l1	ENSMUSG00000024937
rattus_norvegicus	Ehbp1l1	ENSRNOG00000056038
drosophila_melanogaster	Ehbp1	FBGN0034180

Paralogs (7): ASPM (ENSG00000066279), MICALL1 (ENSG00000100139), EHBP1 (ENSG00000115504), GAS2 (ENSG00000148935), MICALL2 (ENSG00000164877), GAS2L1 (ENSG00000185340), SMTNL1 (ENSG00000214872)

Protein

Protein identifiers

EH domain-binding protein 1-like protein 1 — Q8N3D4 (reviewed: Q8N3D4)

All UniProt accessions (4): Q8N3D4, A0A0U1RQH4, E9PIH6, H0YDZ9

UniProt curated annotations — full annotation on UniProt →

Function. May act as Rab effector protein and play a role in vesicle trafficking.

Subunit / interactions. Interacts with RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); at least in case of RAB8A can bind 2 molecules of RAB8A simultaneously; ternary complex formation of RAB8A, RAB13 and EHBP1L1 is possible.

Subcellular location. Endosome.

Post-translational modifications. Prenylated. Farnelysation (predominant) and geranylgeranylation has been observed in vitro.

Domain organisation. The CAAX motif is a signal for prenylation and required for endosomal colocalization with Rab8 and Rab10. The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms).

RefSeq proteins (2): NP_001092879, NP_001338016 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR019448	NT-C2	Domain
IPR022735	bMERB_dom	Domain
IPR036872	CH_dom_sf	Homologous_superfamily
IPR050540	F-actin_Monoox_Mical	Family

Pfam: PF00307, PF10358, PF12130

UniProt features (40 total): modified residue 13, compositionally biased region 10, sequence variant 6, domain 3, region of interest 3, sequence conflict 2, chain 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3D4-F1	49.98	0.12

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 (13): 170, 173, 191, 285, 310, 367, 430, 454, 895, 964, 1168, 1257, 1273

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, chr11q13, RICKMAN_METASTASIS_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_ENDOCYTIC_RECYCLING, GOMF_ACTIN_BINDING, GOBP_LOCALIZATION_WITHIN_MEMBRANE, NAKAMURA_METASTASIS_MODEL_DN, MULLIGHAN_MLL_SIGNATURE_1_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, NUYTTEN_NIPP1_TARGETS_DN, GEORGES_TARGETS_OF_MIR192_AND_MIR215

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): endosome (GO:0005768), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1114 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EHBP1L1	RAB8A	P24407	706
EHBP1L1	RILPL1	Q5EBL4	643
EHBP1L1	TIGD3	Q6B0B8	609
EHBP1L1	RAB10	P61026	567
EHBP1L1	FRMD8	Q9BZ67	537
EHBP1L1	RAB29	O14966	534
EHBP1L1	ASIC4	Q96FT7	509
EHBP1L1	RILPL2	Q969X0	501
EHBP1L1	BUD13	Q9BRD0	493
EHBP1L1	CAMTA1	Q9Y6Y1	482
EHBP1L1	SLC25A45	Q8N413	476
EHBP1L1	FAM89B	Q8N5H3	468
EHBP1L1	ZPR1	O75312	461
EHBP1L1	APOA5	Q6Q788	448
EHBP1L1	KCNK7	Q9Y2U2	442

IntAct

20 interactions, top by confidence:

A	B	Type	Score
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
KANK4	TRAPPC3	psi-mi:“MI:0914”(association)	0.640
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
GPN3	POLR3A	psi-mi:“MI:0914”(association)	0.530
SGF29	MATN2	psi-mi:“MI:0914”(association)	0.530
NUP58	EHBP1L1	psi-mi:“MI:0915”(physical association)	0.400
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
UBXN6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350
RRP7A	EHBP1L1	psi-mi:“MI:0914”(association)	0.350
ANO4	LAGE3	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
SH3KBP1	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
EHBP1L1		psi-mi:“MI:0915”(physical association)	0.000
	EHBP1L1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (59): EHBP1L1 (Co-fractionation), EHBP1L1 (Proximity Label-MS), EHBP1L1 (Co-localization), EHBP1L1 (Co-localization), BIN1 (Co-localization), RAB8A (Co-localization), RAB8B (Co-localization), EHBP1L1 (Affinity Capture-RNA), EHBP1L1 (Affinity Capture-MS), EHBP1L1 (Proximity Label-MS), EHBP1L1 (Proximity Label-MS), EHBP1L1 (Proximity Label-MS), EHBP1L1 (Proximity Label-MS), EHBP1L1 (Proximity Label-MS), EHBP1L1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0J9YX94, A0A0J9YXQ4, A0A0J9YY54, A0A494C1R9, A5D7L8, A6NDY0, A6NKD2, A7E321, E9PGG2, F6SZT2, O14771, O19110, O75807, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0CW24, P17564, P78358, Q01534, Q0P5N2, Q15735, Q2KI51, Q2M329, Q587J8, Q5DTT8, Q5R5G8, Q5R6R8, Q5SV97, Q60465, Q62881, Q69ZB3, Q6P752, Q86V59, Q8BSI6, Q8IWY8, Q8N3D4, Q8VD63

Diamond homologs: A5D7D1, A8MU46, D3ZEN0, D3ZHV2, D3ZQL6, D4A1F2, E1BBG2, E7F9T0, F1MF74, F1QH17, F1QWK4, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O76329, O88990, O94851, O97592, P05094, P05095, P11277, P11530, P11531, P11532, P11533, P12814, P15508, P18091, P20111, P30427, P35609, P46939, P53814, P57780

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	257
Likely benign	16
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3377198	NM_001099409.3(EHBP1L1):c.491+1G>A	Likely pathogenic

SpliceAI

3204 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65579076:A:AG	acceptor_gain	1.0000
11:65579077:G:GG	acceptor_gain	1.0000
11:65579990:G:GG	donor_gain	1.0000
11:65580071:T:TA	acceptor_gain	1.0000
11:65580072:G:A	acceptor_gain	1.0000
11:65580076:CACA:C	acceptor_loss	1.0000
11:65580079:A:AG	acceptor_gain	1.0000
11:65580079:A:T	acceptor_loss	1.0000
11:65580079:AG:A	acceptor_gain	1.0000
11:65580080:G:GA	acceptor_loss	1.0000
11:65580080:G:GG	acceptor_gain	1.0000
11:65580080:GG:G	acceptor_gain	1.0000
11:65580080:GGA:G	acceptor_gain	1.0000
11:65580080:GGAGT:G	acceptor_gain	1.0000
11:65580188:G:GG	donor_gain	1.0000
11:65580207:GC:G	donor_gain	1.0000
11:65580213:C:G	donor_gain	1.0000
11:65580255:GCCAC:G	donor_gain	1.0000
11:65580260:G:GG	donor_gain	1.0000
11:65580335:AG:A	acceptor_gain	1.0000
11:65580336:GG:G	acceptor_gain	1.0000
11:65580475:GCCAG:G	donor_gain	1.0000
11:65580476:CCAGG:C	donor_loss	1.0000
11:65580477:CAGGT:C	donor_loss	1.0000
11:65580478:AGGT:A	donor_loss	1.0000
11:65580479:GG:G	donor_loss	1.0000
11:65580480:G:GA	donor_loss	1.0000
11:65581047:A:AG	acceptor_gain	1.0000
11:65581048:C:G	acceptor_gain	1.0000
11:65581050:A:AG	acceptor_gain	1.0000

AlphaMissense

9712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65579103:T:A	W44R	1.000
11:65579103:T:C	W44R	1.000
11:65579350:T:A	W58R	1.000
11:65579350:T:C	W58R	1.000
11:65579352:G:C	W58C	1.000
11:65579352:G:T	W58C	1.000
11:65579969:T:A	W98R	1.000
11:65579969:T:C	W98R	1.000
11:65576354:T:C	F18L	0.999
11:65576355:T:C	F18S	0.999
11:65576356:C:A	F18L	0.999
11:65576356:C:G	F18L	0.999
11:65576361:T:C	F20S	0.999
11:65576367:C:A	A22D	0.999
11:65576382:T:C	L27P	0.999
11:65576405:T:A	W35R	0.999
11:65576405:T:C	W35R	0.999
11:65579392:T:A	W72R	0.999
11:65579392:T:C	W72R	0.999
11:65579976:T:C	F100S	0.999
11:65580214:T:C	L149P	0.999
11:65580366:T:C	L174P	0.999
11:65584283:T:A	W1046R	0.999
11:65584283:T:C	W1046R	0.999
11:65584343:T:A	W1066R	0.999
11:65584343:T:C	W1066R	0.999
11:65584962:T:C	F1102L	0.999
11:65584964:C:A	F1102L	0.999
11:65584964:C:G	F1102L	0.999
11:65584972:T:C	F1105S	0.999

dbSNP variants (sampled 300 via entrez): RS1000012937 (11:65577270 G>A), RS1000059647 (11:65576721 G>A), RS1000067271 (11:65589446 C>G), RS1000083692 (11:65583449 G>T), RS1000298836 (11:65576407 G>A), RS1000371086 (11:65589202 C>T), RS1000406774 (11:65588921 A>G), RS1000621049 (11:65587152 A>G), RS1000632146 (11:65574862 A>G), RS1000694424 (11:65587429 C>A,T), RS1000723738 (11:65587809 A>C), RS1000737045 (11:65588658 A>G), RS1000921349 (11:65580869 C>T), RS1001046286 (11:65579026 A>T), RS1001087017 (11:65584664 T>C)

Disease associations

OMIM: gene MIM:619583 | disease phenotypes: MIM:236750

GenCC curated gene-disease

Disease	Classification	Inheritance
non-immune hydrops fetalis	Strong	Autosomal recessive

Mondo (1): non-immune hydrops fetalis (MONDO:0009369)

Orphanet (1): Non-immune hydrops fetalis (Orphanet:363999)

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000766_7	Non-alcoholic fatty liver disease histology (lobular)	9.000000e-07
GCST002481_8	Acne (severe)	3.000000e-11
GCST002495_1	Blood pressure (age interaction)	6.000000e-07
GCST002495_2	Blood pressure (age interaction)	3.000000e-07
GCST004605_50	Mean corpuscular hemoglobin concentration	1.000000e-11
GCST004621_25	Red cell distribution width	2.000000e-17
GCST004630_250	Mean corpuscular hemoglobin	1.000000e-11
GCST005194_195	Coronary artery disease	3.000000e-10
GCST005790_22	Rosacea symptom severity	5.000000e-07
GCST006804_95	Red cell distribution width	1.000000e-22
GCST010173_129	Triglyceride levels	2.000000e-10
GCST010866_82	Coronary artery disease	2.000000e-17
GCST011365_143	Myocardial infarction	3.000000e-06
GCST90002390_33	Mean corpuscular hemoglobin	1.000000e-34
GCST90002391_199	Mean corpuscular hemoglobin concentration	2.000000e-15
GCST90002392_349	Mean corpuscular volume	2.000000e-24
GCST90002404_515	Red cell distribution width	3.000000e-61
GCST90020025_1877	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_1494	Waist-hip index	5.000000e-09
GCST90020029_325	Waist circumference adjusted for body mass index	1.000000e-10

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0008007	age at assessment
EFO:0006340	mean arterial pressure
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0009180	rosacea severity measurement
EFO:0004530	triglyceride measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
FR900359	decreases phosphorylation	1
testosterone enanthate	affects expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
entinostat	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dieldrin	decreases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04308603	Not specified	COMPLETED	Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
NCT05528796	Not specified	ENROLLING_BY_INVITATION	Uncovering the Etiologies of Non-immune Hydrops Fetalis