TTC5

protein-coding

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

Gene summary

Enables ribosome binding activity. Involved in positive regulation of mRNA catabolic process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_138376.3

Inheritance

ClinVar variants

P:12U:56B:9

Top phenotype

Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr14:20,256,558-20,305,960

External References & Databases

Ensembl (ENSG00000136319)

Transcript & Mutation Effects

hg38 • Region Span ~49.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphismSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030999

Submitter: PanelApp Australia

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphismSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030999

Submitter: G2P

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphismSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030999

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphismLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030999

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphismAR

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: 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

Refs: 29302074; 32439809

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTC5 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 17

Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphismTotal: 17

TTC5-related disorderTotal: 3

Neurodevelopmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138376.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	5 clinvar		6
missense	2 clinvar	1 clinvar	51 clinvar	3 clinvar	1 clinvar	58
nonsense	1 clinvar	4 clinvar	4 clinvar			9
start loss						0
frameshift	1 clinvar	2 clinvar				3
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	5	7	56	8	1	77

Highest pathogenic variant AF is 0.00004276985

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138376.3	RefSeq	NP_612385.2	10	MANE Select
ENST00000258821.8	Ensembl	ENSP00000258821.3	10	MANE Select
ENST00000383029.7	Ensembl	ENSP00000372496.3	4	Standard
ENST00000553828.1	Ensembl	ENSP00000451259.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription
Regulation of TP53 Activity through Methylation
Regulation of TP53 Activity

Biological Process

DNA repair
positive regulation of transcription by RNA polymerase II
regulation of signal transduction by p53 class mediator

Molecular Function

DNA binding
chromatin binding
protein binding

Cellular Component

nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258821
Coding exons: 10
Length: 49437
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.532	216	239	0.903	0.0000124	2843
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000062	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00076	0.00076	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.565
RVIS EVS: 0.17
RVIS percentile EVS: 65.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0324

Gene Damage Prediction

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