TULP1

TUB like protein 1

Basic information

Region (hg38): 6:35497874-35512896

Previous symbols: [ "RP14" ]

Links

ENSG00000112041 ∙ NCBI:7287 ∙ OMIM:602280 ∙ HGNC:12423 ∙ Uniprot:O00294 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• retinitis pigmentosa 14 (Definitive), mode of inheritance: AR
• Leber congenital amaurosis 15 (Strong), mode of inheritance: AR
• retinitis pigmentosa 14 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leber congenital amaurosis 15; Retinitis pigmentosa 14	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	9462751; 9462750; 15024725; 15557452; 17620573; 18055821; 17962469; 20079931; 21792230; 21987678; 22605927; 22665969

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TULP1 gene.

• not provided (60 variants)
• Leber congenital amaurosis 15 (10 variants)
• Retinitis pigmentosa 14 (9 variants)
• Retinitis pigmentosa (4 variants)
• Retinal dystrophy (4 variants)
• Leber congenital amaurosis 1 (3 variants)
• Leber congenital amaurosis (3 variants)
• Autosomal recessive retinitis pigmentosa (2 variants)
• Syndactyly;Polydactyly, postaxial, type A1;Retinal degeneration;Brachydactyly (1 variants)
• Abnormality of the eye (1 variants)
• Leber congenital amaurosis;Leber congenital amaurosis 15 (1 variants)
• TULP1-related disorder (1 variants)
• Stargardt disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TULP1 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			4	172	1	177
missense	11	16	226	2	5	260
nonsense	22	4	2			28
start loss						0
frameshift	25	9	2			36
inframe indel	1		5	2	1	9
splice donor/acceptor (+/-2bp)	4	12	1			17
splice region	1	1	21	34	1	58
non coding		1	7	105	11	124
Total	63	42	247	281	18

Highest pathogenic variant AF is 0.000105

Variants in TULP1

This is a list of pathogenic ClinVar variants found in the TULP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-35498009-A-C		Retinitis pigmentosa • Leber congenital amaurosis 15	Benign (Jan 13, 2018)
6-35498022-C-T		Leber congenital amaurosis 15 • Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
6-35498049-G-A		Retinitis pigmentosa • Leber congenital amaurosis 15	Uncertain significance (Jan 13, 2018)
6-35498053-AG-A		Retinitis Pigmentosa, Recessive • Leber congenital amaurosis	Likely benign (Jun 14, 2016)
6-35498055-G-C		Retinitis pigmentosa • Leber congenital amaurosis 15	Uncertain significance (Jan 13, 2018)
6-35498059-G-T		Leber congenital amaurosis 15 • Retinitis pigmentosa	Benign (Jan 12, 2018)
6-35498296-G-A		Retinitis pigmentosa • Leber congenital amaurosis 15	Uncertain significance (Jan 12, 2018)
6-35498330-C-T			Likely benign (Sep 12, 2022)
6-35498341-G-A			Likely benign (Aug 02, 2023)
6-35498344-T-C		Leber congenital amaurosis 15	Uncertain significance (Oct 13, 2022)
6-35498344-T-G		Retinitis pigmentosa 14	Uncertain significance (-)
6-35498345-C-A			Uncertain significance (May 08, 2023)
6-35498348-G-A			Likely benign (Nov 22, 2023)
6-35498351-G-T			Uncertain significance (Jul 02, 2022)
6-35498356-T-C			Uncertain significance (Oct 13, 2022)
6-35498359-A-G		Retinitis pigmentosa • not specified	Uncertain significance (Aug 15, 2024)
6-35498363-G-T			Likely benign (Dec 24, 2023)
6-35498365-C-T		Inborn genetic diseases	Uncertain significance (Mar 23, 2023)
6-35498366-G-A			Likely benign (Apr 30, 2023)
6-35498368-T-TGGCGAA		Leber congenital amaurosis 15	Pathogenic (Nov 01, 2007)
6-35498372-G-A			Likely benign (Oct 04, 2023)
6-35498374-AG-A		Retinal dystrophy	Uncertain significance (Jul 12, 2023)
6-35498381-C-G			Likely benign (Nov 08, 2022)
6-35498383-G-A			Likely benign (Nov 13, 2023)
6-35498384-G-C			Likely benign (Mar 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TULP1	protein_coding	protein_coding	ENST00000229771	15	15065

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000568	0.999	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.647	295	328	0.899	0.0000214	3469
Missense in Polyphen		105	129.61	0.81011		1342
Synonymous	0.859	125	138	0.907	0.00000931	1079
Loss of Function	3.22	11	30.1	0.366	0.00000180	338

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000376	0.000363
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000117	0.000114
Middle Eastern	0.000164	0.000163
South Asian	0.000165	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long- term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells (By similarity). Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4- phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages. {ECO:0000250, ECO:0000269|PubMed:16303976, ECO:0000269|PubMed:19837063}.
• Disease: DISEASE: Leber congenital amaurosis 15 (LCA15) [MIM:613843]: 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:15024725, ECO:0000269|PubMed:17962469}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.152

Intolerance Scores

• loftool: 0.104
• rvis_EVS: -0.04
• rvis_percentile_EVS: 50.5

Haploinsufficiency Scores

• pHI: 0.336
• hipred: Y
• hipred_score: 0.516
• ghis: 0.442

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.614

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tulp1
• Phenotype: cellular phenotype; pigmentation 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); 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)

Gene ontology

• Biological process: retina homeostasis;phagocytosis, recognition;visual perception;dendrite development;eye photoreceptor cell development;photoreceptor cell maintenance;positive regulation of phagocytosis;detection of light stimulus involved in visual perception;retina development in camera-type eye;protein localization to cilium;receptor localization to non-motile cilium;protein localization to photoreceptor outer segment
• Cellular component: photoreceptor outer segment;photoreceptor inner segment;extracellular region;cytosol;plasma membrane;cilium;cell junction;cell projection;axon terminus;synapse
• Molecular function: protein binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol binding;actin filament binding