RP1L1

RP1 like 1, the group of Doublecortin superfamily

Basic information

Region (hg38): 8:10606349-10712187

Links

ENSG00000183638 ∙ NCBI:94137 ∙ OMIM:608581 ∙ HGNC:15946 ∙ Uniprot:Q8IWN7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• occult macular dystrophy (Strong), mode of inheritance: AD
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• occult macular dystrophy (Supportive), mode of inheritance: AD
• retinitis pigmentosa 88 (Limited), mode of inheritance: AR
• occult macular dystrophy (Strong), mode of inheritance: AD
• occult macular dystrophy (Definitive), mode of inheritance: AD
• occult macular dystrophy (Strong), mode of inheritance: AD
• retinitis pigmentosa 88 (Strong), mode of inheritance: AR
• cone dystrophy (Limited), mode of inheritance: AR
• retinitis pigmentosa (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Occult macular dystrophy; Retinitis pigmentosa 88	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	2774037; 8909203; 10670483; 12664360; 17317401; 20826268; 22466457; 23281133

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RP1L1 gene.

• Inborn_genetic_diseases (676 variants)
• not_provided (613 variants)
• Occult_macular_dystrophy (384 variants)
• Retinal_dystrophy (263 variants)
• RP1L1-related_disorder (84 variants)
• Retinitis_pigmentosa_88 (66 variants)
• not_specified (46 variants)
• Retinitis_pigmentosa (5 variants)
• Optic_atrophy (3 variants)
• Autosomal_recessive_retinitis_pigmentosa (2 variants)
• Stargardt_disease (1 variants)
• Cone-rod_dystrophy (1 variants)
• Intellectual_disability (1 variants)
• See_cases (1 variants)
• Ulnar/fibula_ray_defect-brachydactyly_syndrome (1 variants)
• Epidermolysis_bullosa_simplex_with_nail_dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RP1L1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000178857.6. 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	61	168	32	263
missense	1	6	902	202	51	1162
nonsense	6	24	21	1		52
start loss			1			1
frameshift	2	14	16	2		34
splice donor/acceptor (+/-2bp)		1	2	1		4
Total	9	47	1003	374	83

Highest pathogenic variant AF is 0.000828798

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RP1L1	protein_coding	protein_coding	ENST00000382483	3	105839

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.82e-10	0.00935	122270	41	2487	124798	0.0102

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-10.1	2394	1.35e+3	1.77	0.0000831	15252
Missense in Polyphen		378	198.14	1.9078		2208
Synonymous	-9.81	889	587	1.51	0.0000401	5094
Loss of Function	-1.76	12	6.99	1.72	3.81e-7	78

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0138	0.0138
Ashkenazi Jewish	0.00	0.00
East Asian	0.0808	0.0801
Finnish	0.0147	0.0146
European (Non-Finnish)	0.00209	0.00205
Middle Eastern	0.0808	0.0801
South Asian	0.00311	0.00311
Other	0.00648	0.00629

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the differentiation of photoreceptor cells. Plays a role in the organization of outer segment of rod and cone photoreceptors (By similarity). {ECO:0000250}.
• Disease: DISEASE: Occult macular dystrophy (OCMD) [MIM:613587]: An inherited macular dystrophy characterized by progressive loss of macular function but normal ophthalmoscopic appearance. It is typically characterized by a central cone dysfunction leading to a loss of vision despite normal ophthalmoscopic appearance, normal fluorescein angiography, and normal full-field electroretinogram (ERGs), but the amplitudes of the focal macular ERGs and multifocal ERGs are significantly reduced at the central retina. {ECO:0000269|PubMed:20826268, ECO:0000269|PubMed:22605915}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.523
• rvis_EVS: 7.25
• rvis_percentile_EVS: 99.9

Haploinsufficiency Scores

• pHI: 0.0918

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0620

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Rp1l1
• 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

Zebrafish Information Network

• Gene name: rp1l1a
• Affected structure: eye
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: visual perception;axoneme assembly;intracellular signal transduction;photoreceptor cell development;photoreceptor cell maintenance;retina development in camera-type eye
• Cellular component: photoreceptor outer segment;microtubule;axoneme;photoreceptor connecting cilium