TTC5

tetratricopeptide repeat domain 5, the group of Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 14:20256558-20305960

Links

ENSG00000136319 ∙ NCBI:91875 ∙ OMIM:619014 ∙ HGNC:19274 ∙ Uniprot:Q8N0Z6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism (Limited), mode of inheritance: AR
• neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism	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	Craniofacial; Neurologic	29302074; 32439809

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TTC5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTC5 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				5		5
missense			23	1	1	25
nonsense		3	2			5
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	3	25	7	1

Variants in TTC5

This is a list of pathogenic ClinVar variants found in the TTC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-20289646-G-A		not specified	Uncertain significance (Aug 10, 2024)
14-20289656-T-C		not specified	Uncertain significance (Feb 05, 2024)
14-20289664-G-C		not specified	Uncertain significance (Aug 30, 2021)
14-20289715-G-A		not specified	Uncertain significance (Mar 27, 2024)
14-20289725-G-A		Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism	Conflicting classifications of pathogenicity (Mar 06, 2024)
14-20292003-G-A		Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism • Neurodevelopmental delay	Uncertain significance (-)
14-20292009-G-A		not specified	Uncertain significance (Nov 13, 2024)
14-20292082-C-A		not specified	Uncertain significance (Dec 06, 2023)
14-20292092-T-G		not specified	Uncertain significance (Mar 05, 2024)
14-20295324-T-C		not specified	Uncertain significance (May 04, 2023)
14-20295343-A-C			Uncertain significance (May 01, 2024)
14-20295370-C-T		not specified	Uncertain significance (Jan 26, 2022)
14-20295393-G-A		not specified	Uncertain significance (Apr 22, 2022)
14-20295416-G-A			Likely benign (Mar 01, 2024)
14-20295444-T-C			Benign (Nov 01, 2024)
14-20295450-C-T		not specified	Uncertain significance (Jun 13, 2024)
14-20295480-C-T		not specified	Uncertain significance (Sep 10, 2024)
14-20295481-G-A		not specified	Uncertain significance (Jun 28, 2024)
14-20295722-G-A		not specified	Uncertain significance (Aug 22, 2023)
14-20295725-T-C		not specified	Uncertain significance (Jan 27, 2022)
14-20295740-G-A			Likely benign (Jul 01, 2023)
14-20295741-G-C		not specified	Uncertain significance (Jan 23, 2024)
14-20295764-G-A		Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism	Pathogenic/Likely pathogenic (-)
14-20295809-A-G		Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism	Likely pathogenic (Dec 18, 2024)
14-20296391-G-A			Uncertain significance (Jan 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTC5	protein_coding	protein_coding	ENST00000258821	10	49437

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000462	0.992	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.532	216	239	0.903	0.0000124	2843
Missense in Polyphen		32	54.571	0.58639		653
Synonymous	-0.0556	94	93.3	1.01	0.00000466	874
Loss of Function	2.37	13	26.0	0.499	0.00000150	277

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000124
Ashkenazi Jewish	0.00	0.00
East Asian	0.000761	0.000761
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000242	0.000237
Middle Eastern	0.000761	0.000761
South Asian	0.000100	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein involved in p53/TP53 response that acts by regulating and mediating the assembly of multi-protein complexes. Required to facilitate the interaction between JMY and p300/EP300 and increase p53/TP53-dependent transcription and apoptosis. Prevents p53/TP53 degradation by MDM2 (By similarity). {ECO:0000250}.
• Pathway: Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Regulation of TP53 Activity through Methylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;p53 pathway (Consensus)

Recessive Scores

• pRec: 0.146

Intolerance Scores

• loftool: 0.565
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.96

Haploinsufficiency Scores

• pHI: 0.206
• hipred: N
• hipred_score: 0.372
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0324

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ttc5

Gene ontology

• Biological process: DNA repair;positive regulation of transcription by RNA polymerase II;regulation of signal transduction by p53 class mediator
• Cellular component: nucleoplasm;cytoplasm
• Molecular function: DNA binding;chromatin binding;protein binding