PROM1
prominin 1, the group of CD molecules
Basic information
Region (hg38): 4:15963076-16084378
Previous symbols: [ "PROML1", "MCDR2", "STGD4" ]
Links
Phenotypes
GenCC
Source:
- Stargardt disease (Supportive), mode of inheritance: AD
- retinitis pigmentosa (Supportive), mode of inheritance: AD
- cone-rod dystrophy (Supportive), mode of inheritance: AD
- retinitis pigmentosa 41 (Definitive), mode of inheritance: AR
- cone-rod dystrophy 12 (Strong), mode of inheritance: AR
- retinal macular dystrophy type 2 (Strong), mode of inheritance: AD
- retinitis pigmentosa 41 (Strong), mode of inheritance: AR
- inherited retinal dystrophy (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cone-rod dystrophy 12; Macular dystrophy, retinal, 2; Stargardt disease 4; Retinitis pigmentosa 41 | 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 | 10205271; 10587575; 12657606; 17605048; 18654668; 20393116; 20859302; 24474277; 26702251; 29416601; 31576780 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (64 variants)
- Retinal dystrophy (11 variants)
- Retinitis pigmentosa 41 (7 variants)
- Cone-rod dystrophy 12 (6 variants)
- Cone-rod dystrophy (5 variants)
- Retinitis pigmentosa (3 variants)
- Stargardt disease (3 variants)
- Retinal macular dystrophy type 2 (2 variants)
- Stargardt disease 4 (2 variants)
- Leber congenital amaurosis 1 (1 variants)
- Isolated macular dystrophy (1 variants)
- Macular dystrophy (1 variants)
- PROM1-related disorder (1 variants)
- Leber congenital amaurosis (1 variants)
- Cone-rod dystrophy 12;Retinitis pigmentosa 41;Stargardt disease 4;Retinal macular dystrophy type 2 (1 variants)
- Retinal macular dystrophy type 2;Retinitis pigmentosa 41 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PROM1 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 | 10 | 110 | 125 | |||
| missense | 384 | 396 | ||||
| nonsense | 24 | 32 | ||||
| start loss | 2 | |||||
| frameshift | 27 | 34 | ||||
| inframe indel | 4 | |||||
| splice donor/acceptor (+/-2bp) | 14 | 20 | 35 | |||
| splice region | 2 | 1 | 34 | 30 | 7 | 74 |
| non coding | 24 | 107 | 34 | 166 | ||
| Total | 66 | 40 | 427 | 222 | 39 |
Highest pathogenic variant AF is 0.0000789
Variants in PROM1
This is a list of pathogenic ClinVar variants found in the PROM1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-15963077-A-G | not specified | Uncertain significance (Dec 07, 2023) | ||
| 4-15968233-T-C | Retinitis pigmentosa • Stargardt disease 4 • Cone-rod dystrophy 12 • Retinal macular dystrophy type 2 | Uncertain significance (Jan 12, 2018) | ||
| 4-15968244-T-C | Cone-rod dystrophy 12 • Retinitis pigmentosa • Stargardt disease 4 • Retinal macular dystrophy type 2 | Uncertain significance (Jan 12, 2018) | ||
| 4-15968250-T-G | Retinal macular dystrophy type 2 • Cone-rod dystrophy 12 • Retinitis pigmentosa • Stargardt disease 4 | Uncertain significance (Jan 12, 2018) | ||
| 4-15968315-T-C | Stargardt disease 4 • Cone-rod dystrophy 12 • Retinitis pigmentosa • Retinal macular dystrophy type 2 | Benign (Jan 13, 2018) | ||
| 4-15968323-T-C | Retinitis pigmentosa • Cone-rod dystrophy 12 • Stargardt disease 4 • Retinal macular dystrophy type 2 | Uncertain significance (Jan 12, 2018) | ||
| 4-15968341-C-T | Stargardt disease 4 • Retinal macular dystrophy type 2 • Cone-rod dystrophy 12 • Retinitis pigmentosa | Conflicting classifications of pathogenicity (Jan 12, 2018) | ||
| 4-15968408-G-C | Retinitis pigmentosa • Stargardt disease 4 • Cone-rod dystrophy 12 • Retinal macular dystrophy type 2 | Uncertain significance (Jan 13, 2018) | ||
| 4-15968430-T-C | Retinitis pigmentosa • Cone-rod dystrophy 12 • Retinal macular dystrophy type 2 • Stargardt disease 4 | Uncertain significance (Jan 12, 2018) | ||
| 4-15968612-C-T | Retinal macular dystrophy type 2 • Cone-rod dystrophy 12 • Stargardt disease 4 • Retinitis pigmentosa | Uncertain significance (Jan 12, 2018) | ||
| 4-15968709-G-A | Retinal macular dystrophy type 2 • Stargardt disease 4 • Cone-rod dystrophy 12 • Retinitis pigmentosa | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 4-15968712-G-C | Cone-rod dystrophy 12 • Stargardt disease 4 • Retinal macular dystrophy type 2 • Retinitis pigmentosa | Uncertain significance (Jan 12, 2018) | ||
| 4-15968726-T-G | Stargardt disease 4 • Cone-rod dystrophy 12 • Retinal macular dystrophy type 2 • Retinitis pigmentosa | Benign (Apr 30, 2020) | ||
| 4-15968753-A-T | Stargardt disease 4 • Retinitis pigmentosa • Retinal macular dystrophy type 2 • Cone-rod dystrophy 12 | Uncertain significance (Jan 12, 2018) | ||
| 4-15968813-A-T | Stargardt disease 4 • Retinitis pigmentosa • Cone-rod dystrophy 12 • Retinal macular dystrophy type 2 | Uncertain significance (Jan 13, 2018) | ||
| 4-15968842-T-A | Cone-rod dystrophy 12 • Stargardt disease 4 • Retinitis pigmentosa • Retinal macular dystrophy type 2 | Uncertain significance (Jan 13, 2018) | ||
| 4-15969195-A-G | Stargardt disease 4 • Retinitis pigmentosa • Retinal macular dystrophy type 2 • Cone-rod dystrophy 12 | Uncertain significance (Jan 12, 2018) | ||
| 4-15969204-T-C | Cone-rod dystrophy 12 • Stargardt disease 4 • Retinal macular dystrophy type 2 • Retinitis pigmentosa | Uncertain significance (Jan 13, 2018) | ||
| 4-15969286-C-A | Retinitis pigmentosa • Cone-rod dystrophy 12 • Retinal macular dystrophy type 2 • Stargardt disease 4 | Uncertain significance (Jan 13, 2018) | ||
| 4-15969308-TC-T | Macular dystrophy, retinal • Cone-Rod Dystrophy, Dominant • Stargardt Disease, Dominant • Retinitis Pigmentosa, Recessive | Likely benign (Jun 14, 2016) | ||
| 4-15971069-A-C | Uncertain significance (Oct 17, 2022) | |||
| 4-15971072-G-T | Uncertain significance (Apr 15, 2021) | |||
| 4-15971075-G-A | Uncertain significance (Oct 23, 2023) | |||
| 4-15971081-G-C | Inborn genetic diseases | Uncertain significance (Sep 27, 2021) | ||
| 4-15971091-C-CA | Benign (Nov 11, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PROM1 | protein_coding | protein_coding | ENST00000510224 | 26 | 121303 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.95e-22 | 0.0399 | 124483 | 0 | 176 | 124659 | 0.000706 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.613 | 478 | 442 | 1.08 | 0.0000232 | 5627 |
| Missense in Polyphen | 150 | 147.2 | 1.019 | 2005 | ||
| Synonymous | 0.111 | 168 | 170 | 0.989 | 0.00000964 | 1621 |
| Loss of Function | 1.26 | 39 | 48.5 | 0.805 | 0.00000245 | 629 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00126 | 0.00125 |
| Ashkenazi Jewish | 0.0000994 | 0.0000994 |
| East Asian | 0.000670 | 0.000668 |
| Finnish | 0.000236 | 0.000232 |
| European (Non-Finnish) | 0.000935 | 0.000920 |
| Middle Eastern | 0.000670 | 0.000668 |
| South Asian | 0.000305 | 0.000294 |
| Other | 0.000834 | 0.000826 |
dbNSFP
Source:
- Function
- FUNCTION: May play a role in cell differentiation, proliferation and apoptosis (PubMed:24556617). Binds cholesterol in cholesterol- containing plasma membrane microdomains and may play a role in the organization of the apical plasma membrane in epithelial cells. During early retinal development acts as a key regulator of disk morphogenesis. Involved in regulation of MAPK and Akt signaling pathways. In neuroblastoma cells suppresses cell differentiation such as neurite outgrowth in a RET-dependent manner (PubMed:20818439). {ECO:0000269|PubMed:20818439, ECO:0000269|PubMed:24556617}.;
- Disease
- DISEASE: Retinitis pigmentosa 41 (RP41) [MIM:612095]: 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:10587575, ECO:0000269|PubMed:17605048}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cone-rod dystrophy 12 (CORD12) [MIM:612657]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors. {ECO:0000269|PubMed:18654668}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Stargardt disease 4 (STGD4) [MIM:603786]: A common hereditary macular degeneration. It is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. {ECO:0000269|PubMed:18654668}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinal macular dystrophy 2 (MCDR2) [MIM:608051]: A bull's-eye macular dystrophy characterized by bilateral annular atrophy of retinal pigment epithelium at the macula. {ECO:0000269|PubMed:18654668}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Transcriptional misregulation in cancer - Homo sapiens (human);Extracellular vesicle-mediated signaling in recipient cells
(Consensus)
Recessive Scores
- pRec
- 0.315
Intolerance Scores
- loftool
- rvis_EVS
- -1.37
- rvis_percentile_EVS
- 4.48
Haploinsufficiency Scores
- pHI
- 0.317
- hipred
- N
- hipred_score
- 0.207
- ghis
- 0.448
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.739
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prom1
- Phenotype
- cellular phenotype; growth/size/body region phenotype; vision/eye 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); pigmentation phenotype; neoplasm; 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- retina layer formation;photoreceptor cell maintenance;retina morphogenesis in camera-type eye;camera-type eye photoreceptor cell differentiation;glomerular visceral epithelial cell differentiation;glomerular parietal epithelial cell differentiation;positive regulation of nephron tubule epithelial cell differentiation
- Cellular component
- photoreceptor outer segment;extracellular space;endoplasmic reticulum;endoplasmic reticulum-Golgi intermediate compartment;plasma membrane;integral component of plasma membrane;microvillus;cilium;cell surface;apical plasma membrane;microvillus membrane;vesicle;photoreceptor outer segment membrane;extracellular exosome;prominosome
- Molecular function
- protein binding;cholesterol binding;actinin binding;cadherin binding