ROR1

Summary

ROR1 (receptor tyrosine kinase like orphan receptor 1, HGNC:10256) is a protein-coding gene on chromosome 1p31.3, encoding Inactive tyrosine-protein kinase transmembrane receptor ROR1 (Q01973). Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo.

This gene encodes a receptor tyrosine kinase-like orphan receptor that modulates neurite growth in the central nervous system. The encoded protein is a glycosylated type I membrane protein that belongs to the ROR subfamily of cell surface receptors. It is a pseudokinase that lacks catalytic activity and may interact with the non-canonical Wnt signalling pathway. This gene is highly expressed during early embryonic development but expressed at very low levels in adult tissues. Increased expression of this gene is associated with B-cell chronic lymphocytic leukaemia. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 4919 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive 108 (Moderate, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 290 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_005012

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10256
Approved symbol	ROR1
Name	receptor tyrosine kinase like orphan receptor 1
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185483
Ensembl biotype	protein_coding
OMIM	602336
Entrez	4919

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371079, ENST00000371080, ENST00000482426

RefSeq mRNA: 2 — MANE Select: NM_005012 NM_001083592, NM_005012

CCDS: CCDS41344, CCDS626

Canonical transcript exons

ENST00000371079 — 9 exons

Exon	Start	End
ENSE00001454303	64177428	64181498
ENSE00001454305	63774017	63774508
ENSE00003516915	64050686	64050716
ENSE00003538526	64137369	64137496
ENSE00003553651	64049691	64049978
ENSE00003559494	64009305	64009376
ENSE00003719568	64158981	64159192
ENSE00003735973	64142405	64142650
ENSE00003746077	64140109	64140426

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 83.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4138 / max 130.4036, expressed in 1109 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3196	6.0786	1102
3197	0.1737	84
3198	0.1615	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	83.40	gold quality
popliteal artery	UBERON:0002250	82.98	gold quality
tibial artery	UBERON:0007610	82.97	gold quality
islet of Langerhans	UBERON:0000006	81.96	gold quality
right coronary artery	UBERON:0001625	81.81	gold quality
lower lobe of lung	UBERON:0008949	81.16	gold quality
aorta	UBERON:0000947	81.00	gold quality
saphenous vein	UBERON:0007318	81.00	gold quality
blood vessel layer	UBERON:0004797	79.90	gold quality
descending thoracic aorta	UBERON:0002345	79.58	gold quality
sural nerve	UBERON:0015488	79.29	gold quality
buccal mucosa cell	CL:0002336	78.80	gold quality
thoracic aorta	UBERON:0001515	78.41	gold quality
ascending aorta	UBERON:0001496	78.11	gold quality
left coronary artery	UBERON:0001626	77.24	gold quality
smooth muscle tissue	UBERON:0001135	77.05	gold quality
coronary artery	UBERON:0001621	76.92	gold quality
parietal pleura	UBERON:0002400	76.82	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.79	gold quality
colonic epithelium	UBERON:0000397	76.21	gold quality
stomach	UBERON:0000945	76.07	gold quality
lung	UBERON:0002048	75.87	gold quality
pancreas	UBERON:0001264	75.56	gold quality
skin of hip	UBERON:0001554	75.25	gold quality
gall bladder	UBERON:0002110	75.09	gold quality
body of stomach	UBERON:0001161	74.90	gold quality
ventricular zone	UBERON:0003053	74.79	gold quality
endocervix	UBERON:0000458	74.74	gold quality
heart	UBERON:0000948	74.19	gold quality
pleura	UBERON:0000977	73.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	14.63
E-ANND-3	yes	5.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

208 targeting ROR1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-188-3P	100.00	68.76	1240
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376

Literature-anchored findings (GeneRIF, showing 40)

• investigation of mutations in GCL modifier subunit and the GCL catalytic subunit that modify catalytic activity and lower glutathione levels (PMID:12954617)
• overexpression of GCLm extended the mean life span only up to 24% (PMID:16148000)
• The ROR1 protein modulates the growth of neurites as well as their branching pattern in hippocampal neurons. (PMID:15654020)
• finsings show ROR1 protein is selectively expressed on the surface of B-cell chronic lymphocytic leukemia (B-CLL) cells, whereas normal B cells, other normal blood cells, and normal adult tissues do not express cell surface ROR1 (PMID:18223214)
• ROR1 is an oncofetal surface antigen and survival-signaling receptor in chronic lymphocytic leukemia. (PMID:18287027)
• Overexpression of orphan receptor tyrosine kinase Ror1 is associated with acute lymphoblastic leukemia (PMID:18354269)
• The majority of CLL cells exhibited Ror1 surface expression (71% mean; range 36-92%). Two different variants of the Ror1 protein, 105 and 130 kDa, were identified. (PMID:18546292)
• expression of ROR1 and WT1 in B-ALL is associated with the differentiation stage of the leukemic cells (PMID:18604725)
• results indicate that ROR1 expression is not limited to chronic lymphoid leukaemia cases, but it is more prevalent in non-Hodgkin lymphomas (PMID:20597086)
• Data suggest that constitutively activated Stat3 binds to the ROR1 promoter and activates ROR1 in CLL cells. (PMID:20686606)
• ROR1 has characteristics of an oncofetal gene and is expressed in undifferentiated embryonic stem cells, B-cell chronic lymphocytic leukemia and mantle cell lymphoma, but not in major adult tissues. (PMID:20702778)
• Detection of a high level of ROR1 expression in blood cells might assist in early detection of renal malignancies. (PMID:21079657)
• Ror1 undergoes complex post-translational modifications by glycosylation and mono-ubiquitination. These modifications regulate Ror1 localization and signalling, and are highly variable among individual chronic lymphocytic leukemia patients. (PMID:21481194)
• Findings suggest a critical role for Ror1 in malignant phenotypes sustained by the Met oncogene. (PMID:21487037)
• ROR1 is uniformly and highly expressed in all in chronic lymphocytic leukemia (CLL) cases at initial diagnosis and can serve as a diagnostic tool. (PMID:21531460)
• A panel of mAbs demonstrated high affinity and specificity for a diverse set of epitopes that involve all three extracellular domains of ROR1, are accessible on the cell surface, and mediate internalization (PMID:21698301)
• ROR1 is expressed on hematogones (non-neoplastic human B-lymphocyte precursors) and a minority of precursor-B acute lymphoblastic leukemia. (PMID:21813176)
• nuclear-localized ROR1 may play an important role in cell migration and cytoskeleton remodeling (PMID:22199287)
• ROR1 was overexpressed in acute lymphoblastic leukemia (PMID:22369092)
• ROR1 is expressed in human breast cancers and has biological and clinical significance (PMID:22403610)
• that the receptor tyrosine kinase ROR1 was overexpressed in most patients with various hematological malignancies of both lymphoid and myeloid origins. (PMID:22988987)
• Many different human cancers express ROR1 and ROR1 may play a functional role in promoting tumor cell growth. (PMID:23041612)
• t(1;19) Acute Lymphoblastic Leukemia cells universally exhibit expression of and dependence on the cell surface receptor ROR1. (PMID:23153538)
• cell surface expression in pediatric B-ALL along with its virtual absence from normal tissues and circulating cells makes ROR1 a promising target for mAb-based therapies. (PMID:23285131)
• Our results show that customizing spacer design and increasing affinity of ROR1-CARs enhances T-cell effector function and recognition of ROR1(+) tumors. (PMID:23620405)
• Data indicate that type I receptor tyrosine kinase-like orphan receptor ROR1 may regulate EMT and metastasis and that antibodies targeting ROR1 can inhibit cancer progression and metastasis. (PMID:23771907)
• Data shows that ROR1 and ROR2 are inversely expressed in melanomas and negatively regulate each other. Also, hypoxia initiates a shift of ROR1-positive melanomas to a more invasive, ROR2-positive phenotype. (PMID:24104062)
• CLL cells expressed different isoforms of ROR1. (PMID:24205204)
• ROR1 can interact with TCL1 and enhance leukemogenesis in Emu-TCL1 transgenic mice. (PMID:24379361)
• ROR1 is only detectable in embryonic tissue and generally absent in adult tissue, making the protein an ideal drug target for cancer therapy. [Review] (PMID:24752542)
• Human ROR1 and ROR2 are receptor tyrosine kinase-like pseudokinases. (PMID:25029443)
• ROR1 expression is correlated with malignant attributes of ovarian cancer and it may serve as a novel prognostic marker in ovarian cancer. (PMID:25056203)
• Data indicate that shRNA silencing of type I receptor tyrosine kinase-like orphan receptor (ROR1) cells, or treatment with anti-ROR1 mAb UC-961 impaired the capacity of ovarian cancer cells to form spheroids or tumor xenografts. (PMID:25411317)
• The newly developed OSU-2S delivery using ROR1-directed immunonanoparticles provide selective targeting of OSU-2S to MCL and other ROR1(+) malignancies, sparing normal B cells. (PMID:25937048)
• Significantly down-regulates the activity of the PI3K/AKT/mTOR signaling pathway. (PMID:25978653)
• Both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells. (PMID:26173023)
• High expression of ROR1 (63%), pAkt (36%), and pCREB (20%) was observed in gastric adenocarcinomas, and expression of these proteins was well intercorrelated. (PMID:26245996)
• Data show that ROR1 contributes to melanoma progression by promoting cell growth and migration. (PMID:26509654)
• Data show that silencing receptor tyrosine kinases (RTKs) ROR2 and ROR1 has a strong inhibitory effect on the ability of ovarian cancer cells to proliferate, migrate and invade. (PMID:26515598)
• Data show that the majority of chronic lymphocytic leukemia (CLL) patients had antibodies against receptor tyrosine kinase ROR1. (PMID:26562161)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ror1	ENSDARG00000015176
mus_musculus	Ror1	ENSMUSG00000035305
rattus_norvegicus	Ror1	ENSRNOG00000029449

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078)

Protein

Protein identifiers

Inactive tyrosine-protein kinase transmembrane receptor ROR1 — Q01973 (reviewed: Q01973)

Alternative names: Neurotrophic tyrosine kinase, receptor-related 1

All UniProt accessions (1): Q01973

UniProt curated annotations — full annotation on UniProt →

Function. Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo. Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling. In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells. Via IGFBP5 ligand, forms a complex with ERBB2 to enhance CREB oncogenic signaling.

Subunit / interactions. Interacts with ERBB2 and IGFBP5.

Subcellular location. Membrane. Cell projection. Axon.

Tissue specificity. Expressed strongly in human heart, lung and kidney, but weakly in the CNS. Isoform Short is strongly expressed in fetal and adult CNS and in a variety of human cancers, including those originating from CNS or PNS neuroectoderm.

Disease relevance. Deafness, autosomal recessive, 108 (DFNB108) [MIM:617654] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q01973-1	Long	yes
Q01973-2	Short, T-ROR1
Q01973-3	3

RefSeq proteins (2): NP_001077061, NP_005003* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR016247	Tyr_kinase_rcpt_ROR	Family
IPR018056	Kringle_CS	Conserved_site
IPR020067	Frizzled_dom	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036790	Frizzled_dom_sf	Homologous_superfamily
IPR038178	Kringle_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00051, PF01392, PF07679, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

UniProt features (77 total): helix 17, strand 13, sequence variant 10, disulfide bond 9, compositionally biased region 4, glycosylation site 4, domain 4, splice variant 3, region of interest 2, binding site 2, topological domain 2, turn 2, signal peptide 1, chain 1, modified residue 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7TNG	X-RAY DIFFRACTION	1.4
6BA5	X-RAY DIFFRACTION	1.62
6TU9	X-RAY DIFFRACTION	1.94
6BAN	X-RAY DIFFRACTION	1.95
5Z55	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01973-F1	69.17	0.26

Antibody-complex structures (SAbDab): 2 — 6BA5, 6BAN

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 (2): 479–487; 506

Post-translational modifications (1): 645

Disulfide bonds (9): 79–131, 170–235, 178–228, 219–260, 248–296, 252–282, 313–391, 334–374, 362–386

Glycosylation sites (4): 47, 66, 184, 315

Mutagenesis-validated functional residues (1):

Position	Phenotype
482	no effect on kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5140745	WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT
R-HSA-3858494	Beta-catenin independent WNT signaling
R-HSA-4086400	PCP/CE pathway

MSigDB gene sets: 251 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, FREAC2_01, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, MODULE_64, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, AAAYRNCTG_UNKNOWN, MODULE_66, GOBP_EAR_DEVELOPMENT

GO Biological Process (9): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), sensory perception of sound (GO:0007605), cell population proliferation (GO:0008283), astrocyte development (GO:0014002), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), inner ear development (GO:0048839), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), protein phosphorylation (GO:0006468), Wnt signaling pathway (GO:0016055)

GO Molecular Function (11): transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), coreceptor activity (GO:0015026), Wnt-protein binding (GO:0017147), signaling receptor activity (GO:0038023), Wnt receptor activity (GO:0042813), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): stress fiber (GO:0001725), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), axon (GO:0030424), signaling receptor complex (GO:0043235), axon terminus (GO:0043679), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
PCP/CE pathway	1
Signal Transduction	1
Signaling by WNT	1
Beta-catenin independent WNT signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
enzyme-linked receptor protein signaling pathway	1
sensory perception of mechanical stimulus	1
cellular process	1
glial cell development	1
astrocyte differentiation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
ear development	1
anatomical structure development	1
phosphorylation	1
protein modification process	1
cell surface receptor signaling pathway	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
signaling receptor activity	1
protein binding	1
molecular transducer activity	1
transmembrane signaling receptor activity	1
Wnt signaling pathway	1
Wnt-protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
actomyosin	1
contractile actin filament bundle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
neuron projection	1
protein-containing complex	1
neuron projection terminus	1

Protein interactions and networks

STRING

1118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ROR1	WNT5A	P41221	988
ROR1	TCL1A	P56279	697
ROR1	PACSIN2	Q9UNF0	632
ROR1	WNT3A	P56704	584
ROR1	CAP1	Q01518	568
ROR1	RORA	P35397	552
ROR1	CAVIN1	Q6NZI2	552
ROR1	CEP70	Q8NHQ1	547
ROR1	EGFR	P00533	541
ROR1	WNT3	P56703	537
ROR1	TCL1B	O95988	530
ROR1	RETNLB	Q9BQ08	490
ROR1	CD8A	P01732	481
ROR1	DCN	P07585	478
ROR1	RETN	Q9HD89	463

IntAct

63 interactions, top by confidence:

A	B	Type	Score
EGFR	ERBB3	psi-mi:“MI:0914”(association)	0.920
PIK3R1	ERBB3	psi-mi:“MI:0914”(association)	0.920
ROR1	SRC	psi-mi:“MI:0915”(physical association)	0.680
ROR1	SRC	psi-mi:“MI:0407”(direct interaction)	0.680
SRC	ROR1	psi-mi:“MI:0217”(phosphorylation reaction)	0.680
FZD7	LRP6	psi-mi:“MI:2364”(proximity)	0.620
FZD7	LRP6	psi-mi:“MI:0914”(association)	0.620
EGFR	ROR1	psi-mi:“MI:0915”(physical association)	0.580
ROR1	EGFR	psi-mi:“MI:0914”(association)	0.580
ROR1	EGFR	psi-mi:“MI:0915”(physical association)	0.580
ROR1	Src	psi-mi:“MI:0915”(physical association)	0.540
ROR1	Src	psi-mi:“MI:0217”(phosphorylation reaction)	0.540
SERPINB13	TTC4	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
ROR1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
ROR1	PLEC	psi-mi:“MI:0915”(physical association)	0.400
Src	ROR1	psi-mi:“MI:0915”(physical association)	0.400
PPM1B	ROR1	psi-mi:“MI:0915”(physical association)	0.370
PPM1F	ROR1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (152): ROR1 (Proximity Label-MS), TOP1 (Negative Genetic), SMARCB1 (Negative Genetic), ROR1 (Negative Genetic), VHL (Negative Genetic), ROR1 (Affinity Capture-MS), PPM1B (Two-hybrid), PPM1F (Two-hybrid), ILKAP (Two-hybrid), PTPRR (Two-hybrid), PTPN6 (Two-hybrid), DUSP14 (Two-hybrid), DUSP18 (Two-hybrid), DUSP19 (Two-hybrid), DUSP21 (Two-hybrid)

ESM2 similar proteins: A4IGL7, D3ZB51, E9PZ19, O75882, O94779, O95970, P00533, P02469, P07942, P13590, P15209, P24503, P24786, P33150, P39038, P55245, P55283, P68500, P97300, P97527, P97546, Q01279, Q01973, Q03351, Q16288, Q16620, Q1EGL2, Q3B7N0, Q3UQ28, Q5IFJ9, Q5IS37, Q5IS82, Q5R945, Q63604, Q6IS24, Q6VNS1, Q7TPD3, Q7TT15, Q8K4Y5, Q8N475

Diamond homologs: A0A7J6K144, O18783, P00734, P06868, P08519, P12545, P14210, P14417, P17945, P20918, P26927, P26928, P80010, Q01177, Q01973, Q08048, Q16609, Q24K22, Q29485, Q2TV78, Q5R537, Q5R8X6, Q76BS1, Q7M323, Q867B7, Q9BH09, Q9V6K3, Q9Z139, A0M8R7, A0M8S8, A1X150, B3MH43, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, O15146

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
WNT5A	up-regulates	ROR1	binding
ROR1	up-regulates	SRC	phosphorylation
hsa-miR-382-5p	“down-regulates quantity by repression”	ROR1	“post transcriptional regulation”
ROR1	“up-regulates activity”	ERBB3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
Signaling by ERBB2 KD Mutants	5	64.1×	4e-06
RAF/MAP kinase cascade	6	11.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of MAPK cascade	6	10.1×	6e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	9.8×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	181
Likely benign	52
Benign	24

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59971	GRCh38/hg38 1p32.1-31.1(chr1:59632500-76730877)x1	Pathogenic

SpliceAI

4569 predictions. Top by Δscore:

Variant	Effect	Δscore
1:64049935:C:T	donor_gain	1.0000
1:64049939:G:GT	donor_gain	1.0000
1:64049974:GTTTG:G	donor_gain	1.0000
1:64049975:T:G	donor_gain	1.0000
1:64049979:G:GG	donor_gain	1.0000
1:64049979:GTA:G	donor_loss	1.0000
1:64050676:A:AG	acceptor_gain	1.0000
1:64050677:T:G	acceptor_gain	1.0000
1:64050717:G:GG	donor_gain	1.0000
1:64102282:GCGAT:G	donor_gain	1.0000
1:64137367:A:AG	acceptor_gain	1.0000
1:64137368:G:GC	acceptor_gain	1.0000
1:64137368:GA:G	acceptor_gain	1.0000
1:64137368:GAGA:G	acceptor_gain	1.0000
1:64137368:GAGAT:G	acceptor_gain	1.0000
1:64137497:G:GA	donor_loss	1.0000
1:64137497:G:GG	donor_gain	1.0000
1:64140107:A:AG	acceptor_gain	1.0000
1:64140108:G:GG	acceptor_gain	1.0000
1:64140108:GCT:G	acceptor_gain	1.0000
1:64140422:TAAAA:T	donor_gain	1.0000
1:64140424:AAA:A	donor_gain	1.0000
1:64140425:AA:A	donor_gain	1.0000
1:64140427:G:GG	donor_gain	1.0000
1:64142584:G:GT	donor_gain	1.0000
1:64158967:A:AG	acceptor_gain	1.0000
1:64158968:T:G	acceptor_gain	1.0000
1:64158972:T:TA	acceptor_gain	1.0000
1:64158975:A:AG	acceptor_gain	1.0000
1:64158976:C:G	acceptor_gain	1.0000

AlphaMissense

6167 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:64049757:T:C	L77P	1.000
1:64049762:T:A	C79S	1.000
1:64049762:T:C	C79R	1.000
1:64049763:G:A	C79Y	1.000
1:64049763:G:C	C79S	1.000
1:64049764:C:G	C79W	1.000
1:64049798:T:A	W91R	1.000
1:64049798:T:C	W91R	1.000
1:64049799:G:C	W91S	1.000
1:64049800:G:C	W91C	1.000
1:64049800:G:T	W91C	1.000
1:64049806:A:C	K93N	1.000
1:64049806:A:T	K93N	1.000
1:64049874:T:C	L116P	1.000
1:64049889:T:A	L121H	1.000
1:64049913:T:C	F129S	1.000
1:64049918:T:A	C131S	1.000
1:64049918:T:C	C131R	1.000
1:64049919:G:A	C131Y	1.000
1:64049919:G:C	C131S	1.000
1:64049920:C:G	C131W	1.000
1:64049958:G:A	G144E	1.000
1:64049970:T:A	V148D	1.000
1:64137394:T:A	C170S	1.000
1:64137394:T:C	C170R	1.000
1:64137395:G:A	C170Y	1.000
1:64137395:G:C	C170S	1.000
1:64137403:T:G	Y173D	1.000
1:64137409:G:A	G175R	1.000
1:64137409:G:C	G175R	1.000

dbSNP variants (sampled 300 via entrez): RS1000004094 (1:64102762 A>G), RS1000004326 (1:64037954 C>G), RS1000007441 (1:64059741 CAGTT>C), RS1000014016 (1:63831341 A>G), RS1000027695 (1:63789696 T>G), RS1000028284 (1:63970969 C>G), RS1000029593 (1:64131219 G>T), RS1000051365 (1:64066340 T>C), RS1000059961 (1:63881036 A>G), RS1000069322 (1:64021841 T>C), RS1000073192 (1:64146909 A>G), RS1000074826 (1:64104250 G>A,T), RS1000111994 (1:63988507 C>A), RS1000118588 (1:63838157 A>G), RS1000128528 (1:64081599 A>C)

Disease associations

OMIM: gene MIM:602336 | disease phenotypes: MIM:617654

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal recessive 108	Moderate	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive
nonsyndromic genetic hearing loss	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Limited	AR

Mondo (3): hearing loss, autosomal recessive 108 (MONDO:0033200), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564609	Deafness, Autosomal Recessive (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4665585 (SINGLE PROTEIN), CHEMBL6195509 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195558 (PROTEIN-PROTEIN INTERACTION)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type VIII RTKs: ROR family

ChEMBL bioactivities

77 potent at pChembl≥5 of 78 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.92	Kd	1.21	nM	CHEMBL6145153
8.80	Kd	1.57	nM	CHEMBL6150322
8.76	Kd	1.72	nM	CHEMBL6152828
8.66	IC50	2.2	nM	CHEMBL5428267
8.53	Kd	2.98	nM	CHEMBL6167251
8.52	Kd	3	nM	CHEMBL5397768
8.28	IC50	5.3	nM	CHEMBL5397895
8.28	IC50	5.2	nM	CHEMBL5399065
8.20	IC50	6.3	nM	CHEMBL5427174
8.14	IC50	7.2	nM	CHEMBL5437151
8.14	IC50	7.2	nM	CHEMBL5408107
8.07	IC50	8.6	nM	CHEMBL5410563
8.00	IC50	10	nM	CHEMBL5396415
8.00	IC50	9.9	nM	CHEMBL5424562
7.96	Kd	11	nM	CHEMBL5416192
7.91	IC50	12.3	nM	CHEMBL5422581
7.89	IC50	13	nM	CHEMBL5416192
7.84	IC50	14.4	nM	CHEMBL5427967
7.75	IC50	17.6	nM	CHEMBL6192385
7.66	Kd	22	nM	CHEMBL5411958
7.58	Kd	26.5	nM	CHEMBL6164860
7.54	Kd	28.5	nM	CHEMBL6103061
7.54	Kd	29	nM	CHEMBL6192385
7.52	Kd	30.4	nM	CHEMBL6192248
7.47	Kd	34	nM	CHEMBL5415252
7.40	Kd	39.8	nM	CHEMBL6142760
7.39	Kd	40.5	nM	CHEMBL6148650
7.18	IC50	66	nM	CHEMBL5411958
7.18	Kd	66.5	nM	CHEMBL6171958
7.10	Kd	80	nM	CHEMBL6190382
7.00	Kd	100	nM	CHEMBL5559059
6.96	Kd	110	nM	CHEMBL5557876
6.92	Kd	119	nM	CHEMBL6191357
6.91	Kd	124	nM	CHEMBL6134237
6.85	Kd	140	nM	CHEMBL5505848
6.83	Kd	147	nM	CHEMBL6134395
6.83	Kd	148	nM	CHEMBL6188793
6.82	Kd	152	nM	CHEMBL6147692
6.80	Kd	160	nM	CHEMBL5559363
6.75	Kd	180	nM	CHEMBL5512504
6.73	Kd	188	nM	CHEMBL6192589
6.70	Kd	200	nM	CHEMBL6191663
6.58	Kd	260	nM	CHEMBL5542135
6.58	Kd	261	nM	CHEMBL6146330
6.55	Kd	284	nM	CHEMBL6192897
6.50	Kd	313	nM	CHEMBL6193424
6.49	IC50	324.6	nM	CHEMBL5559059
6.48	Kd	330	nM	CHEMBL5523378
6.47	Kd	335	nM	CHEMBL6192640
6.46	Kd	348	nM	CHEMBL6193066

PubChem BioAssay actives

39 with measured affinity, of 86 total; 36 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
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-N-(2-amino-2-oxoethyl)-9-benzyl-21-(hydroxymethyl)-12,24,33-tris[(4-hydroxyphenyl)methyl]-15,36-bis(1H-indol-3-ylmethyl)-10-methyl-6,30-bis(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-27-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0022	uM
(3R,9S,12S,15S,21S,24S,30S,33S)-N-(2-amino-2-oxoethyl)-33-benzyl-9,12,15-tris(3-carbamimidamidopropyl)-24-(hydroxymethyl)-30-[(4-hydroxyphenyl)methyl]-28-methyl-5,8,11,14,17,20,23,26,29,32,35-undecaoxo-21-[(4-phenylphenyl)methyl]-1-thia-4,7,10,13,16,19,22,25,28,31,34-undecazacyclohexatriacontane-3-carboxamide	2005019: Binding affinity to full length human His-tagged ROR1 (937 residues ) assessed as dissociation constant by SPR analysis	kd	0.0030	uM
(3S,6S,12R,15S,18S,21S,24S,30S,33S,36S,39S)-N-(2-amino-2-oxoethyl)-6,18-dibenzyl-30-(hydroxymethyl)-3,21,33-tris[(4-hydroxyphenyl)methyl]-24-(1H-indol-3-ylmethyl)-19-methyl-15-(2-methylpropyl)-2,5,8,14,17,20,23,26,29,32,35,38-dodecaoxo-36-propan-2-yl-10-thia-1,4,7,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-12-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0052	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-N,21-bis(2-amino-2-oxoethyl)-9,36-dibenzyl-12-(4-hydroxyphenyl)-24,33-bis[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10-methyl-30-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-6,27-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0053	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-N-(2-amino-2-oxoethyl)-9,36-dibenzyl-30-(3-carbamimidamidopropyl)-21-(hydroxymethyl)-12,24,33-tris[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10-methyl-6-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-27-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0063	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-9,36-dibenzyl-21-(hydroxymethyl)-12,24,33-tris[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10-methyl-6,30-bis(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-27-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0072	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-N-(2-amino-2-oxoethyl)-21-(3-amino-3-oxopropyl)-9,36-dibenzyl-12,24,33-tris[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10-methyl-6,30-bis(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-27-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0072	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-N-(2-amino-2-oxoethyl)-9,36-dibenzyl-12,21,24,33-tetrakis[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10-methyl-6,30-bis(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-27-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0086	uM
3-[(5S,8S,11S,14S,17S,20S,26S,29S,32S,35S,38R)-38-[(2-amino-2-oxoethyl)carbamoyl]-5,32-dibenzyl-8,17,29-tris[(4-hydroxyphenyl)methyl]-26-(1H-indol-3-ylmethyl)-31-methyl-11,35-bis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33,36-dodecaoxo-14-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacont-20-yl]propanoic acid	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0099	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-30-(4-aminobutyl)-N-(2-amino-2-oxoethyl)-9,36-dibenzyl-21-(hydroxymethyl)-12,24,33-tris[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10-methyl-6-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-27-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0100	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-N-(2-amino-2-oxoethyl)-9,36-dibenzyl-21-(hydroxymethyl)-12,24,33-tris[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10-methyl-6,30-bis(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-27-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005019: Binding affinity to full length human His-tagged ROR1 (937 residues ) assessed as dissociation constant by SPR analysis	kd	0.0110	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-N-(2-amino-2-oxoethyl)-9,36-dibenzyl-21-(hydroxymethyl)-12,24,33-tris[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10,27-dimethyl-6,30-bis(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0123	uM
2-[(5S,8S,11S,14S,17S,20S,26S,29S,32S,35S,38R)-38-[(2-amino-2-oxoethyl)carbamoyl]-5,32-dibenzyl-8,17,29-tris[(4-hydroxyphenyl)methyl]-26-(1H-indol-3-ylmethyl)-31-methyl-11,35-bis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33,36-dodecaoxo-14-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacont-20-yl]acetic acid	2005027: Binding affinity to human ROR1 expressed in HEK293 cells by cell based assay	ic50	0.0144	uM
(3R,6S,9S,12S,15S,18S,24S,27S)-15-(2-amino-2-hydroxyethyl)-18,27-dibenzyl-9,24-bis[(4-hydroxyphenyl)methyl]-6-(1H-indol-3-ylmethyl)-16-methyl-12-(2-methylpropyl)-5,8,11,14,17,20,23,26,29-nonaoxo-1-thia-4,7,10,13,16,19,22,25,28-nonazacyclotriacontane-3-carboxamide	2005019: Binding affinity to full length human His-tagged ROR1 (937 residues ) assessed as dissociation constant by SPR analysis	kd	0.0220	uM
(3R,6S,9S,12S,15S,21S,24S,27S,30S,33S,36S)-N-[2-[[2-[[2-[[(2R)-1-amino-6-[(3’,6’-dihydroxy-3-oxospiro[2-benzofuran-1,9’-xanthene]-5-carbonyl)amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]-9,36-dibenzyl-21-(hydroxymethyl)-12,24,33-tris[(4-hydroxyphenyl)methyl]-15-(1H-indol-3-ylmethyl)-10-methyl-6,30-bis(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-27-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2005019: Binding affinity to full length human His-tagged ROR1 (937 residues ) assessed as dissociation constant by SPR analysis	kd	0.0340	uM
N-[3-[4-(methoxymethoxy)phenyl]-1-methylindol-6-yl]-4-methyl-3-[2-(1H-pyrazolo[3,4-b]pyridin-4-yl)ethynyl]benzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1000	uM
3-[2-(6-acetamido-3-pyridinyl)ethynyl]-N-[3-[4-(methoxymethoxy)phenyl]-1-methylindol-6-yl]-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1100	uM
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[1-methyl-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]indol-6-yl]benzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1400	uM
N-[3-[4-(methoxymethoxy)phenyl]-1-methylindol-6-yl]-4-methyl-3-[2-(1H-pyrazolo[5,4-b]pyridin-5-yl)ethynyl]benzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1600	uM
N-[3-(6-fluoro-3-pyridinyl)-1-methylindol-6-yl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.1800	uM
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-N-[3-[4-(methoxymethoxy)phenyl]-1-methylindol-6-yl]-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.2600	uM
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[1-methyl-3-[4-(4-methylpiperazin-1-yl)phenyl]indol-6-yl]benzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.3300	uM
(2R)-5,7-bis(methoxymethoxy)-2-(4-methoxyphenyl)-2,3-dihydrochromen-4-one	2066205: Binding affinity to N-terminal His-tagged ROR1 frizzled domain (61 to 393 residues) (unknown origin) transfected in baculovirus infected High Five cells assessed as dissociation constant by SPR analysis	kd	0.4700	uM
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-N-[3-[4-(2-methoxyethoxy)phenyl]-1-methylindol-6-yl]-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.5700	uM
N-[3-(3-cyanophenyl)-1-methylindol-6-yl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.5800	uM
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-(1-methylindol-6-yl)benzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.6200	uM
N-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-methylindol-6-yl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.7000	uM
N-[3-(4-cyanophenyl)-1-methylindol-6-yl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.7800	uM
N-[3-(3,4-dimethoxyphenyl)-1-methylindol-6-yl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.8500	uM
N-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.8800	uM
N-[3-(2-fluoro-3-pyridinyl)-1-methylindol-6-yl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.9500	uM
N-[3-(6-fluoro-3-pyridinyl)-1-methylindol-6-yl]-4-methyl-3-[2-(1H-pyrazolo[3,4-b]pyridin-4-yl)ethynyl]benzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	1.6500	uM
N-[1-ethyl-3-(6-fluoro-3-pyridinyl)indol-6-yl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	1.8100	uM
3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-N-[1-methyl-3-(4-morpholin-4-ylphenyl)indol-6-yl]benzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	2.4800	uM
N-[3-(6-fluoro-3-pyridinyl)-1-methylindol-6-yl]-4-methyl-3-[2-(1H-pyrrolo[2,3-b]pyridin-5-yl)ethynyl]benzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	4.7500	uM
N-[3-(dimethylamino)phenyl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	2066076: Binding affinity to ROR1 kinase domain (453 to 783 residues) (unknown origin) assessed as dissociation constant by SPR analysis	kd	8.2500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	6
Benzo(a)pyrene	decreases expression, increases methylation	4
trichostatin A	increases expression, affects cotreatment	3
Dexamethasone	affects cotreatment, increases expression	3
Formaldehyde	decreases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
entinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	increases abundance, increases expression, affects methylation	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	2
8-Bromo Cyclic Adenosine Monophosphate	decreases expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression, affects cotreatment	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression, decreases expression	1
butyraldehyde	decreases expression	1
versicolorin A	decreases expression	1
nickel sulfate	decreases expression	1
cupric oxide	decreases expression	1
hydroquinone	decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
cylindrospermopsin	decreases expression	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

40 unique, capped per target: 40 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5358430	Binding	Binding affinity to full length human His-tagged ROR1 (937 residues ) assessed as dissociation constant by SPR analysis	Exploration of macrocyclic peptide binders to the extracellular CRD domain of human receptor tyrosine kinase-like orphan receptor 1 (ROR1). — Bioorg Med Chem Lett

Cellosaurus cell lines

10 cell lines: 7 cancer cell line, 2 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B9R7	Abcam A-549 ROR1 KO	Cancer cell line	Male
CVCL_D7ZL	Ubigene A-549 ROR1 KO	Cancer cell line	Male
CVCL_E0MX	Ubigene HeLa ROR1 KO	Cancer cell line	Female
CVCL_E6RL	Genomeditech CHO-K1 H_ROR1	Spontaneously immortalized cell line	Female
CVCL_E6UT	Genomeditech HEK-293 H_ROR1	Transformed cell line	Female
CVCL_E8II	Jurkat-NFAT-Luc2-ROR1-KO-CD16-V158 clone 2A6	Cancer cell line	Male
CVCL_TJ53	HAP1 ROR1 (-) 1	Cancer cell line	Male
CVCL_TJ54	HAP1 ROR1 (-) 2	Cancer cell line	Male
CVCL_TJ55	HAP1 ROR1 (-) 3	Cancer cell line	Male
CVCL_UE49	293T human ROR1	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations