TULP3

TUB like protein 3

Basic information

Region (hg38): 12:2877223-2941138

Links

ENSG00000078246 ∙ NCBI:7289 ∙ OMIM:604730 ∙ HGNC:12425 ∙ Uniprot:O75386 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hepatorenocardiac degenerative fibrosis (Moderate), mode of inheritance: AR
• hepatorenocardiac degenerative fibrosis (Strong), mode of inheritance: AR
• ciliopathy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hepatorenocardiac degenerative fibrosis	AR	Cardiovascular; Gastrointestinal; Renal	The condition can involve fibrosis affecting multiple organ systems, and medical care (eg, related to cardiac fibrosis) may be beneficial; Liver and renal transplant have been described	Cardiovascular; Gastrointestinal; Renal	35397207

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TULP3 gene.

• Hepatorenocardiac degenerative fibrosis (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TULP3 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				1		1
missense			27	1	2	30
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding			3	1	1	5
Total	2	0	30	3	3

Highest pathogenic variant AF is 0.00000658

Variants in TULP3

This is a list of pathogenic ClinVar variants found in the TULP3 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-2885388-C-T			Likely benign (Mar 05, 2018)
12-2887992-C-T			Likely benign (Dec 31, 2019)
12-2909542-G-A		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
12-2909557-C-T		Hepatorenocardiac degenerative fibrosis	Pathogenic (May 27, 2022)
12-2920804-G-T		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
12-2920815-T-C		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
12-2922262-G-T		Inborn genetic diseases	Uncertain significance (Mar 28, 2024)
12-2922298-A-G		Inborn genetic diseases	Uncertain significance (May 30, 2023)
12-2922327-G-A		Inborn genetic diseases	Uncertain significance (Nov 06, 2023)
12-2922353-C-G			Likely benign (Aug 01, 2022)
12-2922357-G-A		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
12-2922388-G-A		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
12-2930281-C-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
12-2930331-A-G		Inborn genetic diseases	Uncertain significance (Apr 27, 2024)
12-2931050-C-A		Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
12-2931052-G-A		Inborn genetic diseases	Uncertain significance (Mar 27, 2023)
12-2931067-G-A		Inborn genetic diseases	Uncertain significance (May 16, 2022)
12-2931086-TC-T		Hepatorenocardiac degenerative fibrosis	Pathogenic (Mar 01, 2023)
12-2931156-T-G		Hepatorenocardiac degenerative fibrosis • Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
12-2931187-C-T		Inborn genetic diseases	Uncertain significance (Jun 01, 2023)
12-2931188-G-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
12-2933424-C-T		Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
12-2933526-C-T		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
12-2933532-T-C		Hepatorenocardiac degenerative fibrosis	Pathogenic (Feb 23, 2023)
12-2934484-C-T		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TULP3	protein_coding	protein_coding	ENST00000397132	12	63918

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000175	0.969	125614	0	133	125747	0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.257	283	295	0.958	0.0000171	3289
Missense in Polyphen		79	81.609	0.96803		904
Synonymous	-0.478	109	103	1.06	0.00000571	973
Loss of Function	2.01	13	23.5	0.553	0.00000136	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000848	0.000834
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000713	0.000695
Middle Eastern	0.000109	0.000109
South Asian	0.000784	0.000752
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negative regulator of the Shh signaling transduction pathway: recruited to primary cilia via association with the IFT complex A (IFT-A) and is required for recruitment of G protein- coupled receptor GPR161 to cilia, a promoter of PKA-dependent basal repression machinery in Shh signaling. Binds to phosphorylated inositide (phosphoinositide) lipids. Both IFT- A- and phosphoinositide-binding properties are required to regulate ciliary G protein-coupled receptor trafficking. Not involved in ciliogenesis. {ECO:0000269|PubMed:11375483, ECO:0000269|PubMed:20889716}.
• Pathway: H19 action Rb-E2F1 signaling and CDK-β-catenin activity;Signal Transduction;Hedgehog ,off, state;Signaling by Hedgehog (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.0909
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.51

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.294
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.725

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tulp3
• Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands 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); growth/size/body region 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); vision/eye phenotype; limbs/digits/tail 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); skeleton phenotype; embryo phenotype

Gene ontology

• Biological process: neural tube closure;regulation of transcription, DNA-templated;G protein-coupled receptor signaling pathway;brain development;regulation of G protein-coupled receptor signaling pathway;anterior/posterior pattern specification;negative regulation of smoothened signaling pathway involved in ventral spinal cord patterning;central nervous system neuron differentiation;embryonic camera-type eye development;embryonic digit morphogenesis;negative regulation of smoothened signaling pathway;embryonic neurocranium morphogenesis;bone development;bronchus morphogenesis;smoothened signaling pathway involved in dorsal/ventral neural tube patterning;protein localization to cilium;ganglion development;receptor localization to non-motile cilium;negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning;protein localization to photoreceptor outer segment
• Cellular component: extracellular region;nucleus;nucleolus;plasma membrane;cilium;axoneme;ciliary base;9+0 non-motile cilium
• Molecular function: protein binding;phosphatidylinositol-4,5-bisphosphate binding;enzyme binding;phosphatidylinositol binding;protein-containing complex binding;intraciliary transport particle A binding