ERBIN

Summary

ERBIN (erbb2 interacting protein, HGNC:15842) is a protein-coding gene on chromosome 5q12.3, encoding Erbin (Q96RT1). Acts as an adapter for the receptor ERBB2, in epithelia.

This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization. It has also been shown to affect the Ras signaling pathway by disrupting Ras-Raf interaction. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 55914 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 1,014 total
• Druggable target: yes
• MANE Select transcript: NM_001253697

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15842
Approved symbol	ERBIN
Name	erbb2 interacting protein
Location	5q12.3
Locus type	gene with protein product
Status	Approved
Aliases	LAP2
Ensembl gene	ENSG00000112851
Ensembl biotype	protein_coding
OMIM	606944
Entrez	55914

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 26 protein_coding, 7 nonsense_mediated_decay, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000284037, ENST00000380938, ENST00000380943, ENST00000416865, ENST00000503913, ENST00000505822, ENST00000506030, ENST00000506744, ENST00000507128, ENST00000507490, ENST00000508515, ENST00000509946, ENST00000511297, ENST00000511671, ENST00000515185, ENST00000699000, ENST00000699001, ENST00000699002, ENST00000699003, ENST00000699004, ENST00000699005, ENST00000699006, ENST00000699007, ENST00000699008, ENST00000699009, ENST00000699010, ENST00000699011, ENST00000699012, ENST00000699013, ENST00000699014, ENST00000874139, ENST00000874140, ENST00000874141, ENST00000874142, ENST00000874143, ENST00000925652, ENST00000925653, ENST00000925654, ENST00000956966, ENST00000956967

RefSeq mRNA: 6 — MANE Select: NM_001253697 NM_001006600, NM_001253697, NM_001253698, NM_001253699, NM_001253701, NM_018695

CCDS: CCDS34172, CCDS3990, CCDS58951, CCDS58952, CCDS58953, CCDS58954

Canonical transcript exons

ENST00000284037 — 26 exons

Exon	Start	End
ENSE00000749858	66048667	66048781
ENSE00000837126	66013549	66013638
ENSE00000837127	66014669	66014725
ENSE00000837128	66053406	66054951
ENSE00000912221	65992710	65992907
ENSE00000912222	65994747	65994864
ENSE00000912223	66012049	66012127
ENSE00000912224	66021322	66021385
ENSE00000912225	66023290	66023364
ENSE00000912226	66024306	66024450
ENSE00000912227	66025480	66025552
ENSE00000912229	66026302	66026417
ENSE00000912230	66028274	66028343
ENSE00000912231	66038383	66038482
ENSE00000912232	66043077	66043198
ENSE00000912233	66044137	66044310
ENSE00000912234	66046353	66046538
ENSE00000912235	66050783	66050966
ENSE00001082465	66072169	66072291
ENSE00001147720	65988635	65988682
ENSE00001850711	65926575	65926806
ENSE00001896859	66078423	66082546
ENSE00003501162	66076875	66076949
ENSE00003602038	66076316	66076408
ENSE00003676737	66025848	66025977
ENSE00003788322	66075024	66075230

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9650 / max 399.7117, expressed in 1779 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56714	12.4381	1580
56711	3.2377	1385
56710	2.6723	1195
56713	1.4427	741
56712	0.6726	384
203574	0.4335	219
56715	0.0682	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.26	gold quality
lateral globus pallidus	UBERON:0002476	99.21	gold quality
cranial nerve II	UBERON:0000941	98.89	gold quality
globus pallidus	UBERON:0001875	98.72	gold quality
subthalamic nucleus	UBERON:0001906	98.61	gold quality
medial globus pallidus	UBERON:0002477	98.57	gold quality
inferior vagus X ganglion	UBERON:0005363	98.43	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.30	gold quality
medulla oblongata	UBERON:0001896	98.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.26	gold quality
superior vestibular nucleus	UBERON:0007227	98.18	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.11	gold quality
substantia nigra pars compacta	UBERON:0001965	97.85	gold quality
calcaneal tendon	UBERON:0003701	97.55	gold quality
inferior olivary complex	UBERON:0002127	97.52	gold quality
CA1 field of hippocampus	UBERON:0003881	97.15	gold quality
epithelium of nasopharynx	UBERON:0001951	97.14	gold quality
ventral tegmental area	UBERON:0002691	97.12	gold quality
caput epididymis	UBERON:0004358	97.07	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.96	gold quality
corpus epididymis	UBERON:0004359	96.95	gold quality
jejunal mucosa	UBERON:0000399	96.84	gold quality
seminal vesicle	UBERON:0000998	96.64	gold quality
superficial temporal artery	UBERON:0001614	96.62	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.52	gold quality
stromal cell of endometrium	CL:0002255	96.45	gold quality
colonic epithelium	UBERON:0000397	96.44	gold quality
renal medulla	UBERON:0000362	96.40	gold quality
biceps brachii	UBERON:0001507	96.33	gold quality
trabecular bone tissue	UBERON:0002483	96.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	95.75
E-HCAD-25	yes	61.25
E-ANND-3	yes	7.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB, TNF

miRNA regulators (miRDB)

183 targeting ERBIN, 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-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 35)

• PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF (PMID:11821434)
• interacts in vivo with p0071 and may be involved in the organization of adherens junctions and the desmosomes of epithelia (PMID:12047349)
• Erbin is a novel suppressor of Ras signaling by disrupting the Ras-Raf interaction; a negative regulator of the Ras-Raf-Erk signaling pathway (PMID:12379659)
• selective binding and sequestration of this residue in its unphosphorylated state by the Erbin PDZ provides a novel mechanism for regulation of the ErbB2-mediated signaling and oncogenicity (PMID:12444095)
• In this review, erbin is shown to inhibit epidermal growth factor signaling by preventing the activation of the Raf-1 kinase by Ras. (PMID:12966186)
• Erbin is a regulator of Nod2-dependent NF-kappaB signaling with a role in inflammatory responses (PMID:16203728)
• Erbin has a regulatory role in the Ras-Raf-MEK pathway and may inhibit ERK activation by disrupting the Sur-8-Ras/Raf interaction (PMID:16301319)
• Structural analyses reveal that the differences between Erbin PDZ domain and the first PDZ domain of ZO-1 in specificity can be accounted for by two key differences in primary sequence. (PMID:16737969)
• ErbB2, APC, beta-catenin, c-Rel and HTLV-1 Tax were identified as ligands of the PDZ domain of Erbin. (PMID:17100642)
• Results define Erbin as a novel negative modulator of Smad2/Smad3 functions and expand the physiological role of Erbin to the regulation of TGFbeta signaling. (PMID:17591701)
• Both palmitoylation and leucine-rich repeats are required for the plasma membrane localization of ERBIN. (PMID:18498353)
• erbin acts as a negative regulator of beta-catenin/T-cell-factor-dependent gene expression. An erbin mutant with a deletion of the N-terminal leucine-rich repeat allows the PDZ domain of erbin to increase beta-catenin/T-cell-factor-dependent transcription (PMID:18667832)
• Arginine 279, glutamic acid 246 in Smad3 and glutamic acid 1321 in Erbin are important for these proteins binding. (PMID:19013433)
• This review discusses all-intracellular and membrane-associated localization of Densin-180 and its signaling, including a phosphorylation-rich area. (PMID:19187442)
• ERBIN binds to SARA using a domain (amino acids 1208-1265) that also interacts with SMAD2 and SMAD3, which we have called the SSID (SARA- and SMAD-interacting domain) (PMID:21878490)
• Data conclude that LAP2 is widely overexpressed in diverse digestive tract cancers and LAP2beta regulates motility of cancer cells and suggest that LAP2beta may have utility for diagnostics and therapeutics in digestive tract cancers. (PMID:22745766)
• These results unravel a critical role of c-Myb in promoting Erbin transcription in G2/M phase and also predict an unappreciated function of Erbin in cell cycle progression. (PMID:22880131)
• DSG1 and Erbin cooperate to repress MAPK signaling and promote keratinocyte differentiation. (PMID:23524970)
• Data reveal that Erbin is a negative regulator of AKT activation and suggest that Erbin may play a role in breast cancer progression. (PMID:23711387)
• Data suggest that Erbin can interact with Sema4C, and co-expression of Erbin blocks the process of Sema4C-induced epithelial-mesenchymal transition. (PMID:24142719)
• analysis of the C-terminal ligand specificity of the erbin PDZ domain (PMID:24813123)
• Erbin is an ErbB2 regulator for breast tumor formation and progression (PMID:25288731)
• Erbin promotes tumourigenesis and tumour growth in colorectal cancer by stabilizing epidermal growth factor receptor (PMID:25521828)
• Erbin loss accelerates cell cycle though down-regulating p21 and p27 expression. Erbin is a novel negative modulator of Akt1-Skp2-p27 signaling pathway. (PMID:26025650)
• STAT3 activation promotes ERBIN expression and negatively regulates TGF-beta activity by the formation of a STAT3-ERBIN-SMAD2/3 complex. (PMID:28126831)
• Our data uncovered an important role of Erbin in regulating hepatocellular carcinoma (HCC) tumorigenesis through inactivating ERalpha-mediated tumor-suppressive signaling, suggesting a new strategy for tamoxifen therapy in HCC by targeting Erbin/ERalpha signaling axis. (PMID:28192186)
• Erbin interacted with kinase suppressor of Ras 1 (KSR1) and displaced it from the RAF/MEK/ERK complex to prevent signal propagation..These findings establish the scaffold protein Erbin as a negative regulator of EMT and tumorigenesis in colorectal cancer through direct suppression of Akt and RAS/RAF signaling (PMID:29980571)
• miR-23c inhibited cell proliferation and accelerated apoptosis by attenuating ERBB2IP. (PMID:30103114)
• Erbin is mainly localized in endothelial cells in human umbilical veins and plays a critical role in endothelial cell migration and tubular formation via the Smad1/5 pathway. (PMID:30367512)
• Erbb2 interacting protein (ERBB2IP), a known target of miR-23c, was positively regulated by KTN1-AS1. (PMID:30551364)
• Findings show that ERBIN is required for Dsg1 requires to downregulate EGFR/Erk signaling and fully suppress invadopodia formation. (PMID:30655320)
• The leucine-rich repeat signaling scaffolds Shoc2 and Erbin: cellular mechanism and role in disease. (PMID:32558243)
• Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer. (PMID:33707428)
• Exosomal ERBB2IP contributes to tumor growth via elevating PSAT1 expression in non-small cell lung carcinoma. (PMID:37192746)
• Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity. (PMID:38232736)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	erbin	ENSDARG00000044281
mus_musculus	Erbin	ENSMUSG00000021709
rattus_norvegicus	Erbin	ENSRNOG00000047137

Paralogs (31): LRRC7 (ENSG00000033122), PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), LRRC39 (ENSG00000122477), LRCH2 (ENSG00000130224), LRCH1 (ENSG00000136141), LRRC8A (ENSG00000136802), LRRC1 (ENSG00000137269), MFHAS1 (ENSG00000147324), LRRC27 (ENSG00000148814), LRRK1 (ENSG00000154237), LRRC58 (ENSG00000163428), LRRC2 (ENSG00000163827), LRRC18 (ENSG00000165383), LRRC28 (ENSG00000168904), LRRC8E (ENSG00000171017), LRRC8C (ENSG00000171488), LRRC8D (ENSG00000171492), PIDD1 (ENSG00000177595), SCRIB (ENSG00000180900), LRCH3 (ENSG00000186001), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRC69 (ENSG00000214954), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

Erbin — Q96RT1 (reviewed: Q96RT1)

Alternative names: Densin-180-like protein, Erbb2-interacting protein, Protein LAP2

All UniProt accessions (15): A0A8V8TML0, A0A8V8TML4, A0A8V8TML6, A0A8V8TMM1, A0A8V8TN18, A0A8V8TN23, A0A8V8TN29, A0A8V8TP04, A0A8V8TP09, A0A8V8TP15, A0A8V8TPC7, A0A8V8TPD2, B4DIP2, Q96RT1, H0YA04

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated ‘Tyr-1248’ of receptor ERBB2, it may contribute to stabilize this unphosphorylated state. Inhibits NOD2-dependent NF-kappa-B signaling and pro-inflammatory cytokine secretion.

Subunit / interactions. Interacts with ERBB2, BPAG1 and ITGB4. May favor the localization of ERBB2, by restricting its presence to the basolateral membrane of epithelial cells. Also found to interact with ARVCF and delta catenin. Interacts (via C-terminus) with DST Isoform 3 (via N-terminus). Interacts with NOD2 (via CARD domain).

Subcellular location. Cell junction. Hemidesmosome. Nucleus membrane. Basolateral cell membrane.

Tissue specificity. Highly expressed in brain, heart, kidney, muscle and stomach, followed by liver, spleen and intestine.

Similarity. Belongs to the LAP (LRR and PDZ) protein family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q96RT1-1	1	yes
Q96RT1-2	2
Q96RT1-3	3
Q96RT1-4	4
Q96RT1-5	5
Q96RT1-6	6
Q96RT1-7	7
Q96RT1-8	8
Q96RT1-9	9

RefSeq proteins (6): NP_001006600, NP_001240626, NP_001240627, NP_001240628, NP_001240630, NP_061165 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR050614	Synaptic_Scaffolding_LAP-MAGUK	Family
IPR055414	LRR_R13L4/SHOC2-like	Domain

Pfam: PF00595, PF13855, PF23598

UniProt features (89 total): modified residue 21, repeat 17, compositionally biased region 9, sequence conflict 9, splice variant 8, sequence variant 7, strand 7, region of interest 6, turn 2, chain 1, domain 1, helix 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
2H3L	X-RAY DIFFRACTION	1
6Q0N	X-RAY DIFFRACTION	1.18
6Q0M	X-RAY DIFFRACTION	1.2
1MFG	X-RAY DIFFRACTION	1.25
7LUL	X-RAY DIFFRACTION	1.65
2QBW	X-RAY DIFFRACTION	1.8
6UBH	X-RAY DIFFRACTION	1.8
1MFL	X-RAY DIFFRACTION	1.88
6Q0U	X-RAY DIFFRACTION	1.89
3CH8	X-RAY DIFFRACTION	1.9
1N7T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RT1-F1	56.01	0.31

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 (21): 440, 444, 483, 485, 569, 598, 602, 603, 620, 715, 852, 857, 872, 917, 920, 931, 972, 1104, 1158, 1179 …

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-1227986	Signaling by ERBB2
R-HSA-8863795	Downregulation of ERBB2 signaling
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9634285	Constitutive Signaling by Overexpressed ERBB2
R-HSA-9652282	Drug-mediated inhibition of ERBB2 signaling
R-HSA-9664565	Signaling by ERBB2 KD Mutants
R-HSA-9665233	Resistance of ERBB2 KD mutants to trastuzumab
R-HSA-9665244	Resistance of ERBB2 KD mutants to sapitinib
R-HSA-9665245	Resistance of ERBB2 KD mutants to tesevatinib
R-HSA-9665246	Resistance of ERBB2 KD mutants to neratinib
R-HSA-9665247	Resistance of ERBB2 KD mutants to osimertinib
R-HSA-9665249	Resistance of ERBB2 KD mutants to afatinib
R-HSA-9665250	Resistance of ERBB2 KD mutants to AEE788
R-HSA-9665251	Resistance of ERBB2 KD mutants to lapatinib
R-HSA-9665348	Signaling by ERBB2 ECD mutants
R-HSA-9665686	Signaling by ERBB2 TMD/JMD mutants
R-HSA-9665737	Drug resistance in ERBB2 TMD/JMD mutants

MSigDB gene sets: 320 (showing top): E2F_Q4, GCM_MAP4K4, E2F_Q4_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, TAATAAT_MIR126, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_RESPONSE_TO_PEPTIDE, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_SIGNALING_PATHWAY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_RESPONSE_TO_MURAMYL_DIPEPTIDE, SRF_Q5_01

GO Biological Process (17): protein targeting (GO:0006605), cell adhesion (GO:0007155), signal transduction (GO:0007165), epidermal growth factor receptor signaling pathway (GO:0007173), integrin-mediated signaling pathway (GO:0007229), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), response to muramyl dipeptide (GO:0032495), response to lipopolysaccharide (GO:0032496), intracellular signal transduction (GO:0035556), intermediate filament cytoskeleton organization (GO:0045104), basal protein localization (GO:0045175), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070433), cellular response to tumor necrosis factor (GO:0071356), negative regulation of monocyte chemotactic protein-1 production (GO:0071638), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), regulation of gene expression (GO:0010468)

GO Molecular Function (4): signaling receptor binding (GO:0005102), ErbB-2 class receptor binding (GO:0005176), structural constituent of cytoskeleton (GO:0005200), protein binding (GO:0005515)

GO Cellular Component (16): basement membrane (GO:0005604), nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), basolateral plasma membrane (GO:0016323), nuclear speck (GO:0016607), cell junction (GO:0030054), hemidesmosome (GO:0030056), neuromuscular junction (GO:0031594), nuclear membrane (GO:0031965), glutamatergic synapse (GO:0098978), postsynaptic specialization (GO:0099572), membrane (GO:0016020), anchoring junction (GO:0070161), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Drug resistance in ERBB2 KD mutants	8
RHO GTPase cycle	7
Signaling by ERBB2	2
Signaling by ERBB2 in Cancer	2
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse	3
cellular process	2
response to oxygen-containing compound	2
intracellular anatomical structure	2
cytoskeleton organization	2
plasma membrane region	2
establishment of protein localization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ERBB signaling pathway	1
cell surface receptor signaling pathway	1
response to nitrogen compound	1
response to molecule of bacterial origin	1
response to lipid	1
signal transduction	1
intermediate filament-based process	1
intracellular protein localization	1
establishment or maintenance of apical/basal cell polarity	1
negative regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	1
nucleotide-binding oligomerization domain containing 2 signaling pathway	1
regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1
negative regulation of chemokine production	1
monocyte chemotactic protein-1 production	1
regulation of monocyte chemotactic protein-1 production	1
regulation of biological quality	1
gene expression	1
regulation of macromolecule biosynthetic process	1
protein binding	1
signaling receptor binding	1
structural molecule activity	1
cytoskeleton	1
binding	1
extracellular matrix	1
intracellular membrane-bounded organelle	1
membrane	1

Protein interactions and networks

STRING

2609 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERBIN	ERBB2	P04626	993
ERBIN	NOD2	Q9HC29	892
ERBIN	DSG1	Q02413	877
ERBIN	ZFYVE9	O95405	827
ERBIN	LMNB1	P20700	818
ERBIN	ITGB4	P16144	789
ERBIN	DST	Q03001	784
ERBIN	CTNND2	Q9UQB3	758
ERBIN	SHOC2	Q9UQ13	750
ERBIN	PKP4	Q99569	740
ERBIN	ARVCF	O00192	733
ERBIN	EGFR	P00533	722
ERBIN	TMPO	P08918	721
ERBIN	SMAD2	Q15796	653
ERBIN	DLG4	P78352	637

IntAct

526 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
ERBIN	PKP4	psi-mi:“MI:0915”(physical association)	0.730
PKP4	ERBIN	psi-mi:“MI:0407”(direct interaction)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
NOD2	ERBIN	psi-mi:“MI:0915”(physical association)	0.660
NOD2	ERBIN	psi-mi:“MI:0403”(colocalization)	0.660
ERBIN	NOD2	psi-mi:“MI:0915”(physical association)	0.660
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
ERBIN	CTNND2	psi-mi:“MI:0915”(physical association)	0.610
ERBIN	ARVCF	psi-mi:“MI:0915”(physical association)	0.610
ERBIN	GAS2L2	psi-mi:“MI:0915”(physical association)	0.610
ERBIN	E6	psi-mi:“MI:0915”(physical association)	0.610
E	ERBIN	psi-mi:“MI:0915”(physical association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
ARVCF	ERBIN	psi-mi:“MI:0407”(direct interaction)	0.610
GAS2L2	ERBIN	psi-mi:“MI:0407”(direct interaction)	0.610

BioGRID (368): ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Proximity Label-MS), ERBB2IP (Proximity Label-MS), ERBB2IP (Proximity Label-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS)

ESM2 similar proteins: A1A5X2, A5PK13, A6H639, A7SFP1, A8XWW4, B0W6M9, B3LWU3, B3P3E8, B4IBI9, B4JTV9, B4LXW1, B4N9T4, B4PU77, B4QVR7, B5DX45, D3ZXS4, O61967, P28191, P34284, Q0VD31, Q14160, Q22875, Q3UM45, Q4H4B6, Q4R642, Q5BJ29, Q5JU00, Q5M8G4, Q6GPJ5, Q7KIN0, Q7KRY7, Q7SXW3, Q7XNY1, Q80TH2, Q80U72, Q80VQ1, Q8BGI7, Q8BH70, Q8CI70, Q8K3W2

Diamond homologs: A0A8C0TYJ0, A0A8P0N4K0, A5PKA5, F1MCA7, G5ECY0, O14907, O14910, O35274, O35867, O55164, O61967, O62674, O62675, O62676, O88951, O88952, P31016, P57105, P70175, P70587, P78352, P97879, Q0P5E6, Q0P5F3, Q12959, Q13424, Q13425, Q13884, Q14160, Q15599, Q22638, Q28626, Q28C55, Q2KIB6, Q32LE7, Q32LM6, Q3T0C9, Q3UHD6, Q4H4B6, Q5EBL8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ARVCF	“up-regulates activity”	ERBIN	binding
CTNND2	“up-regulates activity”	ERBIN	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 199 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	43.3×	3e-09
Activation of BAD and translocation to mitochondria	7	43.0×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	37.9×	5e-08
Activation of BH3-only proteins	7	28.0×	4e-07
Intrinsic Pathway for Apoptosis	8	18.9×	8e-07
RHO GTPases activate PKNs	7	17.9×	8e-06
EPHA-mediated growth cone collapse	5	15.3×	7e-04
Apoptosis	10	13.5×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
regulation of ERK1 and ERK2 cascade	5	17.4×	2e-03
embryonic skeletal system morphogenesis	7	16.4×	3e-04
ephrin receptor signaling pathway	6	12.4×	2e-03
positive regulation of protein localization to plasma membrane	7	11.4×	1e-03
cellular response to retinoic acid	7	9.8×	2e-03
cell surface receptor protein tyrosine kinase signaling pathway	7	7.3×	8e-03
intracellular protein localization	9	5.6×	6e-03
cell migration	14	5.2×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1014 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	598
Likely benign	326
Benign	46

Top pathogenic / likely-pathogenic (0)

SpliceAI

4137 predictions. Top by Δscore:

Variant	Effect	Δscore
5:65992695:A:AG	acceptor_gain	1.0000
5:65992695:ATTC:A	acceptor_gain	1.0000
5:65992704:TTGCA:T	acceptor_loss	1.0000
5:65992706:GCAGT:G	acceptor_loss	1.0000
5:65992707:CAGTG:C	acceptor_loss	1.0000
5:65992708:A:AG	acceptor_gain	1.0000
5:65992708:AGTG:A	acceptor_loss	1.0000
5:65992709:G:A	acceptor_loss	1.0000
5:65992709:G:GA	acceptor_gain	1.0000
5:65992709:GT:G	acceptor_gain	1.0000
5:65992905:AAG:A	donor_gain	1.0000
5:65992906:AG:A	donor_gain	1.0000
5:65992907:GG:G	donor_gain	1.0000
5:65992907:GGTA:G	donor_loss	1.0000
5:65992908:G:GG	donor_gain	1.0000
5:65992908:GTAT:G	donor_loss	1.0000
5:65992909:T:A	donor_loss	1.0000
5:65994742:A:AG	acceptor_gain	1.0000
5:65994743:A:G	acceptor_gain	1.0000
5:65994745:A:AG	acceptor_gain	1.0000
5:65994746:G:A	acceptor_loss	1.0000
5:65994746:G:GT	acceptor_gain	1.0000
5:65994746:GC:G	acceptor_gain	1.0000
5:65994746:GCA:G	acceptor_gain	1.0000
5:65994746:GCAA:G	acceptor_gain	1.0000
5:65994746:GCAAC:G	acceptor_gain	1.0000
5:65994860:GAATG:G	donor_gain	1.0000
5:65994862:ATGG:A	donor_loss	1.0000
5:65994865:G:GA	donor_loss	1.0000
5:65994865:G:GG	donor_gain	1.0000

AlphaMissense

9383 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:65992798:T:C	L27P	1.000
5:65992828:T:A	V37D	1.000
5:65992870:T:A	L51H	1.000
5:65992870:T:C	L51P	1.000
5:65992886:T:A	N56K	1.000
5:65992886:T:G	N56K	1.000
5:65994778:T:C	L74P	1.000
5:65994794:T:A	N79K	1.000
5:65994794:T:G	N79K	1.000
5:65994829:T:C	L91P	1.000
5:65994838:T:A	L94H	1.000
5:65994838:T:C	L94P	1.000
5:65994847:T:C	L97P	1.000
5:65994863:T:A	N102K	1.000
5:65994863:T:G	N102K	1.000
5:66012116:C:A	N125K	1.000
5:66012116:C:G	N125K	1.000
5:66013596:T:C	L145P	1.000
5:66014695:T:C	L168P	1.000
5:66014698:G:T	R169I	1.000
5:66014705:C:A	N171K	1.000
5:66014705:C:G	N171K	1.000
5:66021354:T:C	L189P	1.000
5:66026330:T:C	L350P	1.000
5:66026336:T:C	L352P	1.000
5:66026346:T:A	N355K	1.000
5:66026346:T:G	N355K	1.000
5:66026415:T:A	N378K	1.000
5:66026415:T:G	N378K	1.000
5:66028276:T:C	L380S	1.000

dbSNP variants (sampled 300 via entrez): RS1000006724 (5:66073802 A>G), RS1000010478 (5:65939507 T>C), RS1000012120 (5:65952516 TG>T), RS1000014037 (5:66033145 T>C), RS1000024906 (5:65980382 C>A,T), RS1000033256 (5:65980675 C>T), RS1000041031 (5:66071493 A>C), RS1000055081 (5:66067315 C>T), RS1000106896 (5:66067527 G>A), RS1000137384 (5:66003574 T>A), RS1000147934 (5:66033455 G>A), RS1000161041 (5:66058344 G>A,C,T), RS1000187774 (5:66034966 G>C,T), RS1000212112 (5:66046229 G>A,C), RS1000278479 (5:65956097 C>T)

Disease associations

OMIM: gene MIM:606944 | disease phenotypes: MIM:601357

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal dominant combined immunodeficiency due to ERBIN deficiency	Limited	AD

Mondo (3): amelia cleft lip palate hydrocephalus iris coloboma (MONDO:0011052), prostate cancer (MONDO:0008315), combined immunodeficiency (MONDO:0015131)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003422_5	Squamous cell carcinoma	4.000000e-06
GCST007000_2	Logical memory (delayed recall) in mild cognitive impairment	8.000000e-07
GCST012490_152	Femur bone mineral density x serum urate levels interaction	4.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C536713	Yim Ebbin syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5483009 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Valproic Acid	affects expression, increases methylation	2
Cadmium Chloride	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	decreases phosphorylation	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
Rosiglitazone	increases expression, decreases reaction	1
Pioglitazone	decreases reaction, increases expression	1
Fulvestrant	increases methylation	1
Troglitazone	affects cotreatment, decreases expression, decreases reaction, increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5383470	Binding	Inhibition of N-terminal GST-tagged Erbin (unknown origin) expressed in Escherichia coli BL21 (DE3) cells/P0071 (unknown origin) complex incubated for 16 hrs by HTRF assay	Discovery of a PDZ Domain Inhibitor Targeting the Syndecan/Syntenin Protein-Protein Interaction: A Semi-Automated “Hit Identification-to-Optimization” Approach. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer