CRB1
crumbs cell polarity complex component 1, the group of Crumbs complex
Basic information
Region (hg38): 1:197268203-197478455
Previous symbols: [ "RP12" ]
Links
Phenotypes
GenCC
Source:
- Leber congenital amaurosis 8 (Definitive), mode of inheritance: AR
- retinitis pigmentosa (Supportive), mode of inheritance: AD
- Leber congenital amaurosis (Supportive), mode of inheritance: AD
- nanophthalmia (Supportive), mode of inheritance: AD
- pigmented paravenous retinochoroidal atrophy (Supportive), mode of inheritance: AD
- Leber congenital amaurosis 8 (Strong), mode of inheritance: AR
- retinitis pigmentosa 12 (Definitive), mode of inheritance: AR
- pigmented paravenous retinochoroidal atrophy (Limited), mode of inheritance: AD
- Leber congenital amaurosis 8 (Strong), mode of inheritance: AR
- retinitis pigmentosa 12 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Leber congenital amaurosis 8; Retinitis pigmentosa 12, autosomal recessive; Pigmented paravenous chorioretinal atrophy | AD/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 | Ophthalmologic | 434087; 6614113; 3778279; 2801856; 10508521; 11389483; 15024725; 15623792; 16543197; 16564825; 19140180; 20006823; 21484995; 22065545; 22277662; 23077403; 23379534 |
ClinVar
This is a list of variants' phenotypes submitted to
- Retinitis pigmentosa 12;Leber congenital amaurosis 8 (770 variants)
- Leber congenital amaurosis 8;Retinitis pigmentosa 12 (507 variants)
- Leber congenital amaurosis 8 (354 variants)
- Retinitis pigmentosa 12 (218 variants)
- Pigmented paravenous retinochoroidal atrophy (203 variants)
- not provided (194 variants)
- Leber congenital amaurosis (168 variants)
- Retinitis pigmentosa (100 variants)
- Retinal dystrophy (81 variants)
- Inborn genetic diseases (45 variants)
- not specified (33 variants)
- Leber congenital amaurosis 1 (20 variants)
- Retinitis pigmentosa 12;Pigmented paravenous retinochoroidal atrophy;Leber congenital amaurosis 8 (12 variants)
- Pigmented paravenous retinochoroidal atrophy;Leber congenital amaurosis 8;Retinitis pigmentosa 12 (9 variants)
- CRB1-Related Disorders (7 variants)
- Autosomal recessive retinitis pigmentosa (7 variants)
- Leber congenital amaurosis 8;Pigmented paravenous retinochoroidal atrophy;Retinitis pigmentosa 12 (6 variants)
- Macular dystrophy (6 variants)
- CRB1-related maculopathy (4 variants)
- Leber congenital amaurosis 8;Retinitis pigmentosa 12;Pigmented paravenous retinochoroidal atrophy (4 variants)
- Cone-rod dystrophy (4 variants)
- Early-onset retinal dystrophy (3 variants)
- Retinitis pigmentosa 12;Leber congenital amaurosis 8;Pigmented paravenous retinochoroidal atrophy (3 variants)
- Retinitis Pigmentosa, Recessive (3 variants)
- Cone dystrophy (2 variants)
- CRB1-related condition (2 variants)
- Pigmented paravenous retinochoroidal atrophy;Retinitis pigmentosa 12;Leber congenital amaurosis 8 (2 variants)
- Intellectual disability (2 variants)
- Abnormality of the eye (1 variants)
- Retinitis pigmentosa-deafness syndrome (1 variants)
- CRB1-related disorder (1 variants)
- Stargardt disease (1 variants)
- Autosomal recessive bestrophinopathy (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRB1 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 | 435 | 444 | ||||
| missense | 37 | 90 | 472 | 20 | 619 | |
| nonsense | 59 | 29 | 88 | |||
| start loss | 0 | |||||
| frameshift | 84 | 45 | 131 | |||
| inframe indel | 12 | |||||
| splice donor/acceptor (+/-2bp) | 21 | 30 | ||||
| splice region ? | 3 | 8 | 25 | 36 | ||
| non coding ? | 16 | 50 | 25 | 94 | ||
| Total | 191 | 189 | 499 | 509 | 30 |
Highest pathogenic variant AF is 0.000204
Variants in CRB1
This is a list of pathogenic ClinVar variants found in the CRB1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-197268209-C-T | Retinitis pigmentosa • Leber congenital amaurosis 8 • Pigmented paravenous retinochoroidal atrophy | Uncertain significance (Jan 13, 2018) | ||
| 1-197268218-G-A | Retinitis pigmentosa • Leber congenital amaurosis 8 • Pigmented paravenous retinochoroidal atrophy | Uncertain significance (Jan 13, 2018) | ||
| 1-197268357-C-G | Retinitis pigmentosa • Leber congenital amaurosis 8 • Pigmented paravenous retinochoroidal atrophy | Uncertain significance (Apr 27, 2017) | ||
| 1-197268358-C-T | Retinitis pigmentosa • Leber congenital amaurosis 8 • Pigmented paravenous retinochoroidal atrophy | Uncertain significance (Jan 13, 2018) | ||
| 1-197268411-C-G | Retinal dystrophy | Uncertain significance (Oct 01, 2023) | ||
| 1-197268416-G-A | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Uncertain significance (Jun 13, 2022) | ||
| 1-197268416-GC-G | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Pathogenic (Nov 14, 2022) | ||
| 1-197268421-T-C | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Likely benign (Apr 03, 2022) | ||
| 1-197268424-G-A | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Likely benign (Jan 16, 2021) | ||
| 1-197268426-A-G | Retinitis pigmentosa 12;Leber congenital amaurosis 8 | Uncertain significance (Jul 26, 2022) | ||
| 1-197268427-C-T | Retinitis pigmentosa 12;Leber congenital amaurosis 8 | Likely benign (Jan 31, 2024) | ||
| 1-197268428-AT-A | Retinitis pigmentosa 12 • Retinitis pigmentosa 12;Leber congenital amaurosis 8 | Pathogenic/Likely pathogenic (May 24, 2023) | ||
| 1-197268429-TTAAC-T | Retinitis pigmentosa • Retinitis pigmentosa 12 • Leber congenital amaurosis 8 • Retinitis pigmentosa 12;Leber congenital amaurosis 8 | Pathogenic (Apr 11, 2023) | ||
| 1-197268436-C-T | Retinitis pigmentosa 12;Leber congenital amaurosis 8 | Likely benign (Sep 12, 2022) | ||
| 1-197268441-T-C | Retinitis pigmentosa 12;Leber congenital amaurosis 8 • Leber congenital amaurosis 8 | Conflicting classifications of pathogenicity (Jan 18, 2024) | ||
| 1-197268442-C-T | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Likely benign (Jun 05, 2023) | ||
| 1-197268452-C-T | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Uncertain significance (Aug 09, 2022) | ||
| 1-197268454-C-G | Retinitis pigmentosa 12;Leber congenital amaurosis 8 | Likely benign (Feb 05, 2022) | ||
| 1-197268466-G-A | Retinitis pigmentosa 12;Leber congenital amaurosis 8 | Likely benign (Dec 20, 2023) | ||
| 1-197268466-G-GT | Retinitis pigmentosa | Pathogenic (Jun 24, 2020) | ||
| 1-197268467-C-CT | Leber congenital amaurosis 8 • Inborn genetic diseases • Leber congenital amaurosis 8;Retinitis pigmentosa 12 • Retinitis pigmentosa 12 | Pathogenic (May 13, 2023) | ||
| 1-197268472-C-T | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Likely benign (Dec 26, 2023) | ||
| 1-197268474-A-G | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Uncertain significance (Apr 25, 2022) | ||
| 1-197268475-C-A | Pathogenic (Aug 01, 2016) | |||
| 1-197268477-T-A | Leber congenital amaurosis 8;Retinitis pigmentosa 12 | Uncertain significance (Sep 17, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CRB1 | protein_coding | protein_coding | ENST00000367400 | 12 | 276994 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 5.63e-16 | 0.982 | 125643 | 0 | 105 | 125748 | 0.000418 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -1.28 | 822 | 725 | 1.13 | 0.0000363 | 9340 |
| Missense in Polyphen | 258 | 249.03 | 1.036 | 3278 | ||
| Synonymous | -0.791 | 294 | 277 | 1.06 | 0.0000154 | 2632 |
| Loss of Function | 2.57 | 33 | 53.2 | 0.620 | 0.00000254 | 718 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000717 | 0.000716 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.000870 | 0.000870 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000503 | 0.000501 |
| Middle Eastern | 0.000870 | 0.000870 |
| South Asian | 0.000229 | 0.000229 |
| Other | 0.000655 | 0.000652 |
dbNSFP
Source:
- Function
- FUNCTION: Plays a role in photoreceptor morphogenesis in the retina. May maintain cell polarization and adhesion.;
- Disease
- DISEASE: Note=CRB1 mutations have been found in various retinal dystrophies, chronic and disabling disorders of visual function. They predominantly involve the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the retina, retinal pigment epithelium, Bruch membrane, choroid, or a combination of these tissues. Onset of inherited retinal dystrophies is painless, bilateral and typically progressive. Most people experience gradual peripheral vision loss or tunnel vision, and difficulties with poor illumination and night vision. Central vision is usually unaffected, so the person may still be able to read. However, it can also deteriorate to cause total blindness. Examples of retinal dystrophies are retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy among others. {ECO:0000269|PubMed:20683928, ECO:0000269|PubMed:22065545, ECO:0000269|PubMed:28819299}.; DISEASE: Retinitis pigmentosa 12 (RP12) [MIM:600105]: 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. RP12 is an autosomal recessive, severe form often manifesting in early childhood. Patients experiment progressive visual field loss with severe visual impairment before the age of twenty. Some patients have a preserved paraarteriolar retinal pigment epithelium (PPRPE) and hypermetropia. {ECO:0000269|PubMed:10508521, ECO:0000269|PubMed:11389483, ECO:0000269|PubMed:11559858, ECO:0000269|PubMed:12573663, ECO:0000269|PubMed:12843338, ECO:0000269|PubMed:15459956, ECO:0000269|PubMed:19140180, ECO:0000269|PubMed:19956407, ECO:0000269|PubMed:20591486, ECO:0000269|PubMed:20956273, ECO:0000269|PubMed:21987686, ECO:0000269|PubMed:22065545, ECO:0000269|PubMed:22128245, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:28819299}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leber congenital amaurosis 8 (LCA8) [MIM:613835]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:11231775, ECO:0000269|PubMed:11389483, ECO:0000269|PubMed:12567265, ECO:0000269|PubMed:12573663, ECO:0000269|PubMed:12700176, ECO:0000269|PubMed:12843338, ECO:0000269|PubMed:15024725, ECO:0000269|PubMed:15459956, ECO:0000269|PubMed:15691574, ECO:0000269|PubMed:16205573, ECO:0000269|PubMed:16936081, ECO:0000269|PubMed:17128490, ECO:0000269|PubMed:17438615, ECO:0000269|PubMed:17724218, ECO:0000269|PubMed:18055821, ECO:0000269|PubMed:18682808, ECO:0000269|PubMed:20108431, ECO:0000269|PubMed:20956273, ECO:0000269|PubMed:21602930, ECO:0000269|PubMed:28819299}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pigmented paravenous chorioretinal atrophy (PPCRA) [MIM:172870]: Unusual retinal degeneration characterized by accumulation of pigmentation along retinal veins. PPCRA is dominantly inherited, but exhibited variable expressivity. Males are more likely to exhibit a severe phenotype, whereas females may remain virtually asymptomatic even in later years. The PPCRA phenotype is associated with a mutation in CRB1 gene which is likely to affect the structure of the CRB1 protein. {ECO:0000269|PubMed:15623792}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Hippo signaling pathway - Homo sapiens (human)
(Consensus)
Recessive Scores
- pRec
- 0.195
Intolerance Scores
- loftool
- 0.0401
- rvis_EVS
- -2.56
- rvis_percentile_EVS
- 0.84
Haploinsufficiency Scores
- pHI
- 0.280
- hipred
- N
- hipred_score
- 0.474
- ghis
- 0.581
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.633
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Crb1
- Phenotype
- endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; 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); 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); pigmentation 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); vision/eye phenotype; immune system phenotype;
Gene ontology
- Biological process
- plasma membrane organization;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;establishment or maintenance of cell polarity;cell-cell signaling;eye photoreceptor cell development;establishment or maintenance of epithelial cell apical/basal polarity
- Cellular component
- photoreceptor inner segment;extracellular region;plasma membrane;microvillus;cell-cell adherens junction;integral component of membrane;apical plasma membrane;protein-containing complex
- Molecular function
- calcium ion binding;protein binding