PROM1

prominin 1, the group of CD molecules

Basic information

Region (hg38): 4:15963076-16084378

Previous symbols: [ "PROML1", "MCDR2", "STGD4" ]

Links

ENSG00000007062 ∙ NCBI:8842 ∙ OMIM:604365 ∙ HGNC:9454 ∙ Uniprot:O43490 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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
• retinal macular dystrophy type 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the PROM1 gene.

• not_provided (896 variants)
• Retinal_dystrophy (145 variants)
• Inborn_genetic_diseases (116 variants)
• Cone-rod_dystrophy_12 (113 variants)
• Retinal_macular_dystrophy_type_2 (98 variants)
• Stargardt_disease_4 (95 variants)
• Retinitis_pigmentosa (85 variants)
• Retinitis_pigmentosa_41 (42 variants)
• PROM1-related_disorder (30 variants)
• Cone-rod_dystrophy (14 variants)
• not_specified (12 variants)
• Stargardt_disease (8 variants)
• Autosomal_recessive_retinitis_pigmentosa (4 variants)
• Cone-rod_dystrophy_2 (3 variants)
• Leber_congenital_amaurosis_1 (2 variants)
• Leber_congenital_amaurosis (2 variants)
• Stargardt_Disease,_Dominant (2 variants)
• Retinitis_Pigmentosa,_Recessive (2 variants)
• Cone-Rod_Dystrophy,_Dominant (2 variants)
• Usher_syndrome (2 variants)
• Macular_dystrophy,_retinal (2 variants)
• Isolated_macular_dystrophy (1 variants)
• Retinal_disorders (1 variants)
• Macular_dystrophy (1 variants)
• Optic_atrophy (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. These statistics are base on transcript: NM_000006017.3. 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	1		17	135	5	158
missense	2	11	455	41	1	510
nonsense	33	9	2			44
start loss	2					2
frameshift	42	13	1			56
splice donor/acceptor (+/-2bp)	15	25	3			43
Total	95	58	478	176	6

Highest pathogenic variant AF is 0.000331189

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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