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ROR1

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

Basic information

Region (hg38): 1:63774016-64181498

Previous symbols: [ "NTRKR1" ]

Links

ENSG00000185483NCBI:4919OMIM:602336HGNC:10256Uniprot:Q01973AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Deafness, autosomal recessive 108ARAudiologic/OtolaryngologicEarly recognition and treatment of hearing impairment may possibly benefit developmental outcomes in some individuals, including speech and language developmentAudiologic/Otolaryngologic27162350

ClinVar

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

  • not provided (99 variants)
  • Inborn genetic diseases (30 variants)
  • Hearing loss, autosomal recessive 108 (7 variants)

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
24
clinvar
9
clinvar
33
missense
70
clinvar
3
clinvar
1
clinvar
74
nonsense
0
start loss
0
frameshift
0
inframe indel
1
clinvar
1
splice donor/acceptor (+/-2bp)
1
clinvar
1
splice region
1
1
2
non coding
2
clinvar
13
clinvar
15
Total 0 0 72 29 23

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)1235539
1-63774426-G-A Likely benign (Jan 20, 2023)2812612
1-63774431-G-T Inborn genetic diseases Uncertain significance (Nov 08, 2022)2323769
1-63774433-C-A Uncertain significance (Jan 11, 2024)2964495
1-63774440-G-A Uncertain significance (Dec 21, 2023)1933914
1-63774451-C-T Uncertain significance (Sep 07, 2022)2061856
1-63774459-G-GGCGCTGCTGGCC Uncertain significance (Sep 30, 2023)1509071
1-63774471-C-T Likely benign (Jul 20, 2023)2975684
1-63774491-G-A Inborn genetic diseases Uncertain significance (Nov 06, 2022)2257395
1-63774516-G-T Likely benign (Nov 27, 2023)1647648
1-63774569-C-T Benign (May 14, 2021)1268836
1-64009132-C-T Benign (May 14, 2021)1238957
1-64009249-A-G Benign (May 24, 2021)1260821
1-64009315-G-A Likely benign (Nov 02, 2022)2713771
1-64009337-C-T Inborn genetic diseases Uncertain significance (May 23, 2023)2550512
1-64009338-C-G Uncertain significance (Feb 18, 2021)1471609
1-64009338-C-T Inborn genetic diseases Uncertain significance (Oct 26, 2022)2206763
1-64009377-G-A Uncertain significance (Sep 08, 2023)2749573
1-64009387-G-T Benign (Jan 11, 2024)1585811
1-64049683-G-T Benign (Oct 25, 2022)1599733
1-64049707-C-T Hearing loss, autosomal recessive 108 Benign (Jan 31, 2024)1240716
1-64049734-G-A Benign/Likely benign (Jan 22, 2024)1574543
1-64049738-C-G Uncertain significance (Mar 04, 2023)2722209
1-64049782-A-T Likely benign (Oct 29, 2023)2841904
1-64049796-G-A Uncertain significance (Jan 15, 2023)2901002

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ROR1protein_codingprotein_codingENST00000371079 9407489
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9960.00355125741071257480.0000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.173735110.7300.00002866147
Missense in Polyphen137225.590.607312612
Synonymous1.091711900.9000.00001061867
Loss of Function4.79434.30.1170.00000165437

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002890.0000289
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00003520.0000352
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.0001640.000163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

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