TTC1

protein-coding

tetratricopeptide repeat domain 1, the group of Tetratricopeptide repeat domain containing

Gene summary

This gene encodes a protein that belongs to the tetratrico peptide repeat superfamily of proteins. The encoded protein plays a role in protein-protein interactions, and binds to the Galpha subunit of G protein-coupled receptors to activate the Ras signaling pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MANE transcript

NM_003314.3

Inheritance

—

ClinVar variants

P:1U:40B:2

Top phenotype

Abnormal brain morphology

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr5:160,009,113-160,065,543

External References & Databases

Ensembl (ENSG00000113312)

Transcript & Mutation Effects

hg38 • Region Span ~56.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 1

Abnormal brain morphologyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003314.3. 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			1
missense		1 clinvar	34 clinvar	2 clinvar		37
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	1	40	2	0	43

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003314.3	RefSeq	NP_003305.1	7	MANE Select
ENST00000231238.10	Ensembl	ENSP00000231238.4	7	MANE Select
NM_001282500.2	RefSeq	NP_001269429.1	7	Standard
ENST00000518560.1	Ensembl	ENSP00000428613.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein folding

Molecular Function

protein binding
unfolded protein binding

Cellular Component

peroxisomal membrane
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000231238
Coding exons: 7
Length: 56431
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125747
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.659	125	148	0.847	0.00000719	1940
Missense (PolyPhen)		19	33.847	0.56135		426
Synonymous	0.437	54	58.2	0.927	0.00000334	495
Loss of Function	1.23	11	16.4	0.672	8.39e-7	215

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0016	0.0016	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00010	0.000097	rare
South Asian	0.00020	0.00020	rare
Other	0.00049	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.137

Intolerance Scores

LoFtool: 0.776
RVIS EVS: 0.13
RVIS percentile EVS: 63.2

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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