CLRN1

clarin 1, the group of Clarins

Basic information

Region (hg38): 3:150926163-150972727

Previous symbols: [ "USH3", "USH3A", "RP61" ]

Links

ENSG00000163646 ∙ NCBI:7401 ∙ OMIM:606397 ∙ HGNC:12605 ∙ Uniprot:P58418 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Usher syndrome type 3A (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Usher syndrome type 3 (Supportive), mode of inheritance: AR
• Usher syndrome type 3A (Definitive), mode of inheritance: AR
• retinitis pigmentosa 61 (Strong), mode of inheritance: AR
• retinitis pigmentosa 61 (Strong), mode of inheritance: AR
• Usher syndrome type 3A (Strong), mode of inheritance: AR
• Usher syndrome type 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 61; Usher sydnrome, type 3A	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Ophthalmologic	7711740; 8975700; 9719374; 11524702; 12080385; 12145752; 14569126; 15521980; 19753315; 21310491; 21675857
Hearing loss has been reported to be postlingual

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLRN1 gene.

• not_provided (270 variants)
• Usher_syndrome_type_3A (70 variants)
• Usher_syndrome_type_3 (56 variants)
• Retinitis_pigmentosa_61 (51 variants)
• Inborn_genetic_diseases (34 variants)
• Retinal_dystrophy (34 variants)
• not_specified (19 variants)
• CLRN1-related_disorder (12 variants)
• Usher_syndrome (10 variants)
• Retinitis_pigmentosa (9 variants)
• Rare_genetic_deafness (5 variants)
• Neuronal_ceroid_lipofuscinosis (4 variants)
• Hearing_impairment (3 variants)
• Optic_atrophy (1 variants)
• Melnick-Fraser_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLRN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000174878.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	91	1	94
missense	8	16	114	2		140
nonsense	8	14				22
start loss	1	2				3
frameshift	16	20				36
splice donor/acceptor (+/-2bp)	3	6				9
Total	36	58	116	93	1

Highest pathogenic variant AF is 0.00028073802

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLRN1	protein_coding	protein_coding	ENST00000328863	4	46837

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.71e-8	0.0688	125520	2	226	125748	0.000907

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.593	150	131	1.15	0.00000667	1603
Missense in Polyphen		63	49.408	1.2751		600
Synonymous	0.243	49	51.2	0.957	0.00000304	482
Loss of Function	-0.488	11	9.39	1.17	4.98e-7	112

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000630	0.000630
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.00712	0.00705
European (Non-Finnish)	0.000423	0.000422
Middle Eastern	0.000218	0.000217
South Asian	0.00	0.00
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a role in the excitatory ribbon synapse junctions between hair cells and cochlear ganglion cells and presumably also in analogous synapses within the retina. {ECO:0000269|PubMed:12080385}.
• Disease: DISEASE: Retinitis pigmentosa 61 (RP61) [MIM:614180]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:21310491}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.147

Intolerance Scores

• loftool: 0.641
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.75

Haploinsufficiency Scores

• pHI: 0.182
• hipred: N
• hipred_score: 0.123
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clrn1
• Phenotype: hearing/vestibular/ear 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: clrn1
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased functionality

Gene ontology

• Biological process: actin filament organization;visual perception;sensory perception of sound;positive regulation of lamellipodium assembly;photoreceptor cell maintenance;cell motility;response to stimulus;sensory perception of light stimulus;equilibrioception;auditory receptor cell stereocilium organization
• Cellular component: microtubule;plasma membrane;microvillus;integral component of membrane;lamellipodium;trans-Golgi network transport vesicle;stereocilium;basal part of cell