TTI1

protein-coding

TELO2 interacting protein 1, the group of Armadillo like helical domain containing|TTT complex

Gene summary

Enables kinase binding activity and protein-containing complex stabilizing activity. Involved in positive regulation of DNA damage checkpoint and regulation of TOR signaling. Acts upstream of or within protein stabilization. Located in cytoplasm. Part of TORC1 complex; TORC2 complex; and TTT Hsp90 cochaperone complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

KIAA0406

MANE transcript

NM_001303457.2

Inheritance

ClinVar variants

P:12U:207B:27

Top phenotype

Neurodevelopmental disorder with microcephaly and movement abnormalities

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr20:37,983,007-38,033,461

External References & Databases

Ensembl (ENSG00000101407)

Transcript & Mutation Effects

hg38 • Region Span ~50.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with microcephaly and movement abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957531

Submitter: Broad Center for Mendelian Genomics

neurodevelopmental disorder with microcephaly and movement abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957531

Submitter: PanelApp Australia

microcephalyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001149

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with microcephaly and movement abnormalitiesAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

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: 36724785

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TTI1 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 179

not providedTotal: 50

Neurodevelopmental disorder with microcephaly and movement abnormalitiesTotal: 15

not specifiedTotal: 5

Neurodevelopmental disorderTotal: 2

Severe intellectual disabilityTotal: 2

TTI1-related conditionTotal: 1

Abnormal brain morphologyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001303457.2. 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	17 clinvar	3 clinvar	21
missense	2 clinvar	5 clinvar	195 clinvar	7 clinvar		209
nonsense		2 clinvar	5 clinvar			7
start loss						0
frameshift		1 clinvar	4 clinvar			5
splice donor/acceptor (+/-2bp)	2 clinvar		2 clinvar			4
Total	4	8	207	24	3	246

Highest pathogenic variant AF is 0.00003965166

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001303457.2	RefSeq	NP_001290386.1	7	MANE Select
ENST00000373447.8	Ensembl	ENSP00000362546.3	7	MANE Select
NM_014657.3	RefSeq	NP_055472.1	7	Standard
ENST00000373448.6	Ensembl	ENSP00000362547.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mTOR signaling pathway - Homo sapiens (human)
Steatosis AOP

Biological Process

regulation of TOR signaling

Molecular Function

protein binding

Cellular Component

cytoplasm
TORC1 complex
TORC2 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373448
Coding exons: 7
Length: 50462
Individuals with no LoFs: 125681
Homozygous LoFs: 0
Heterozygous LoFs: 67
Defined: 125748
p: 0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.220	545	560	0.974	0.0000306	7075
Missense (PolyPhen)		132	146.41	0.90156		1854
Synonymous	-0.720	236	222	1.06	0.0000118	2223
Loss of Function	2.42	21	36.9	0.570	0.00000185	485

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.0012	0.0012	notable
East Asian	0.00049	0.00049	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00023	0.00023	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. {ECO:0000269|PubMed:20427287, ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650}.;

Recessive Scores

pRec: 0.0939

Intolerance Scores

RVIS EVS: -0.52
RVIS percentile EVS: 20.94

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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