TTC8

tetratricopeptide repeat domain 8, the group of BBSome|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 14:88824152-88881078

Links

ENSG00000165533 ∙ NCBI:123016 ∙ OMIM:608132 ∙ HGNC:20087 ∙ Uniprot:Q8TAM2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 51 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 8 (Definitive), mode of inheritance: AR
• Bardet-Biedl syndrome 8 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Bardet-Biedl syndrome (Supportive), mode of inheritance: AR
• Bardet-Biedl syndrome 8 (Moderate), mode of inheritance: AR
• Bardet-Biedl syndrome 8 (Strong), mode of inheritance: AR
• retinitis pigmentosa 51 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bardet-Biedl syndrome 8	AR	Cardiovascular; Endocrine	The condition can involve congenital cardiac anomalies, and awareness may allow early management; Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic; Renal	14520415; 16308660; 20301537; 20451172; 36356613

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTC8 gene.

• Bardet-Biedl syndrome (344 variants)
• Bardet-Biedl syndrome 8 (51 variants)
• Retinitis pigmentosa (42 variants)
• not provided (27 variants)
• Retinitis pigmentosa 51 (24 variants)
• not specified (21 variants)
• Inborn genetic diseases (21 variants)
• Retinitis pigmentosa 51;Bardet-Biedl syndrome 8 (19 variants)
• TTC8-related condition (17 variants)
• Bardet-Biedl syndrome 8;Retinitis pigmentosa 51 (16 variants)
• Retinal dystrophy (4 variants)
• Macular dystrophy (1 variants)
• Intellectual disability, moderate;Truncal obesity;Postaxial foot polydactyly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTC8 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			3	64		67
missense			188	1		189
nonsense	4	7	1			12
start loss			3			3
frameshift	8	12	2			22
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	10	1			13
splice region	1		9	9	1	20
non coding		1	13	36	7	57
Total	14	30	214	101	7

Highest pathogenic variant AF is 0.00000659

Variants in TTC8

This is a list of pathogenic ClinVar variants found in the TTC8 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-88824664-C-T		Retinitis pigmentosa • Bardet-Biedl syndrome 8	Uncertain significance (Jan 13, 2018)
14-88824670-C-A		Bardet-Biedl syndrome 8 • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
14-88824683-G-A		Bardet-Biedl syndrome 8 • Retinitis pigmentosa • TTC8-related disorder	Conflicting classifications of pathogenicity (Aug 16, 2021)
14-88824688-C-A		TTC8-related disorder	Likely benign (Aug 23, 2021)
14-88824708-A-G		Bardet-Biedl syndrome	Uncertain significance (Apr 17, 2022)
14-88824708-A-T		Bardet-Biedl syndrome	Uncertain significance (Oct 13, 2022)
14-88824709-T-C		Bardet-Biedl syndrome	Uncertain significance (Feb 26, 2021)
14-88824711-A-G		Bardet-Biedl syndrome • Bardet-Biedl syndrome 8;Retinitis pigmentosa 51 • Inborn genetic diseases • TTC8-related disorder	Conflicting classifications of pathogenicity (Jan 18, 2024)
14-88824712-G-A		Retinitis pigmentosa • Bardet-Biedl syndrome 8 • Bardet-Biedl syndrome • Retinal dystrophy	Conflicting classifications of pathogenicity (Oct 01, 2023)
14-88824712-G-T		Bardet-Biedl syndrome	Uncertain significance (Jan 27, 2022)
14-88824715-C-G		Bardet-Biedl syndrome	Uncertain significance (Aug 09, 2022)
14-88824715-C-T		Bardet-Biedl syndrome	Uncertain significance (Jul 04, 2021)
14-88824729-C-T		Bardet-Biedl syndrome	Likely benign (Aug 14, 2023)
14-88824730-T-A		Bardet-Biedl syndrome	Uncertain significance (Nov 15, 2022)
14-88824741-T-G		Bardet-Biedl syndrome	Uncertain significance (Jul 08, 2021)
14-88824750-T-C		Bardet-Biedl syndrome • Bardet-Biedl syndrome 8;Retinitis pigmentosa 51	Uncertain significance (May 11, 2022)
14-88824759-A-C		Bardet-Biedl syndrome	Likely benign (Jul 23, 2022)
14-88824761-G-A		Bardet-Biedl syndrome • Retinitis pigmentosa 51;Bardet-Biedl syndrome 8	Likely benign (May 04, 2022)
14-88824769-A-G		Bardet-Biedl syndrome	Uncertain significance (May 10, 2021)
14-88824769-A-T		Bardet-Biedl syndrome	Uncertain significance (Dec 02, 2022)
14-88824770-G-A		Retinal dystrophy	Uncertain significance (Oct 01, 2023)
14-88824775-GC-G		Bardet-Biedl syndrome 8	Likely pathogenic (Feb 01, 2020)
14-88824776-C-T		Bardet-Biedl syndrome	Likely benign (Jan 29, 2024)
14-88824780-G-T		Bardet-Biedl syndrome	Uncertain significance (Sep 06, 2022)
14-88824785-A-AT		Bardet-Biedl syndrome 8	Likely pathogenic (Mar 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTC8	protein_coding	protein_coding	ENST00000380656	15	53839

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000118	0.998	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0790	282	278	1.01	0.0000145	3379
Missense in Polyphen		157	163.45	0.96054		1995
Synonymous	1.58	82	102	0.801	0.00000559	949
Loss of Function	2.69	15	31.2	0.481	0.00000143	387

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.000109	0.000109
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization. {ECO:0000269|PubMed:17574030, ECO:0000269|PubMed:22072986}.
• Disease: DISEASE: Bardet-Biedl syndrome 8 (BBS8) [MIM:615985]: A syndrome characterized by usually severe pigmentary retinopathy, early- onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. {ECO:0000269|PubMed:14520415, ECO:0000269|PubMed:16308660}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Olfactory bulb development and olfactory learning;BBSome-mediated cargo-targeting to cilium;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.201

Intolerance Scores

• loftool: 0.651
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.54

Haploinsufficiency Scores

• pHI: 0.212
• hipred: Y
• hipred_score: 0.540
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.272

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ttc8
• 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; renal/urinary system phenotype; respiratory system phenotype; 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); taste/olfaction phenotype; craniofacial phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: ttc8
• Affected structure: pharyngeal arch 3-7
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: protein transport;establishment of anatomical structure orientation;sensory processing;cilium assembly;non-motile cilium assembly
• Cellular component: centrosome;cytosol;cilium;BBSome;ciliary basal body;ciliary membrane;non-motile cilium
• Molecular function: RNA polymerase II repressing transcription factor binding;protein binding