ROR1

receptor tyrosine kinase like orphan receptor 1, the group of I-set domain containing|Receptor tyrosine kinases

Basic information

Region (hg38): 1:63774017-64181498

Previous symbols: [ "NTRKR1" ]

Links

ENSG00000185483 ∙ NCBI:4919 ∙ OMIM:602336 ∙ HGNC:10256 ∙ Uniprot:Q01973 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive 108 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive 108 (Limited), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• hearing loss, autosomal recessive 108 (Limited), mode of inheritance: Unknown
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 108	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may possibly benefit developmental outcomes in some individuals, including speech and language development	Audiologic/Otolaryngologic	27162350

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ROR1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ROR1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				37	8	45
missense			94	3	1	98
nonsense						0
start loss						0
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region				2	1	3
non coding				3	13	16
Total	0	0	97	43	22

Variants in ROR1

This is a list of pathogenic ClinVar variants found in the ROR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-63774394-G-A			Benign (May 22, 2021)
1-63774426-G-A			Likely benign (Jan 20, 2023)
1-63774431-G-T		not specified	Uncertain significance (Nov 08, 2022)
1-63774433-C-A		not specified	Uncertain significance (Jan 11, 2024)
1-63774440-G-A			Uncertain significance (Dec 21, 2023)
1-63774451-C-T			Uncertain significance (Sep 07, 2022)
1-63774459-G-GGCGCTGCTGGCC			Uncertain significance (Sep 30, 2023)
1-63774471-C-T			Likely benign (Jul 20, 2023)
1-63774491-G-A		not specified	Uncertain significance (Nov 06, 2022)
1-63774516-G-T			Likely benign (Nov 27, 2023)
1-63774569-C-T			Benign (May 14, 2021)
1-64009132-C-T			Benign (May 14, 2021)
1-64009249-A-G			Benign (May 24, 2021)
1-64009315-G-A			Likely benign (Nov 02, 2022)
1-64009337-C-T		not specified	Uncertain significance (May 23, 2023)
1-64009338-C-G			Uncertain significance (Feb 18, 2021)
1-64009338-C-T		not specified	Uncertain significance (Oct 26, 2022)
1-64009377-G-A			Uncertain significance (Sep 08, 2023)
1-64009387-G-T			Benign (Jan 11, 2024)
1-64049683-G-T			Benign (Oct 25, 2022)
1-64049707-C-T		Hearing loss, autosomal recessive 108	Benign (Jan 31, 2024)
1-64049734-G-A			Benign/Likely benign (Jan 22, 2024)
1-64049738-C-G			Uncertain significance (Mar 04, 2023)
1-64049766-A-G		not specified	Uncertain significance (Dec 16, 2023)
1-64049782-A-T			Likely benign (Oct 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ROR1	protein_coding	protein_coding	ENST00000371079	9	407489

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00355	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.17	373	511	0.730	0.0000286	6147
Missense in Polyphen		137	225.59	0.60731		2612
Synonymous	1.09	171	190	0.900	0.0000106	1867
Loss of Function	4.79	4	34.3	0.117	0.00000165	437

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (PubMed:25029443). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (PubMed:25029443, PubMed:27162350). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350). {ECO:0000269|PubMed:25029443, ECO:0000269|PubMed:27162350}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:27162350}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Nuclear Receptors;Wnt Signaling Pathway;Wnt Signaling Pathway;Signaling by WNT;Signal Transduction;WNT5A-dependent internalization of FZD2, FZD5 and ROR2;PCP/CE pathway;Beta-catenin independent WNT signaling;Wnt (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.189
• rvis_EVS: -1.59
• rvis_percentile_EVS: 3.05

Haploinsufficiency Scores

• pHI: 0.888
• hipred: Y
• hipred_score: 0.728
• ghis: 0.601

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.403

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ror1
• Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: transmembrane receptor protein tyrosine kinase signaling pathway;sensory perception of sound;astrocyte development;peptidyl-tyrosine phosphorylation;positive regulation of I-kappaB kinase/NF-kappaB signaling;inner ear development;anatomical structure development;positive regulation of NF-kappaB transcription factor activity;Wnt signaling pathway, planar cell polarity pathway
• Cellular component: stress fiber;plasma membrane;integral component of plasma membrane;cell surface;axon;receptor complex;axon terminus
• Molecular function: transmembrane receptor protein tyrosine kinase activity;protein binding;ATP binding;Wnt-protein binding;Wnt-activated receptor activity;coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway