TTI2 (TELO2 interacting protein 2)

Gene

• Entrez ID: 80185
• Gene name: TELO2 interacting protein 2
• Gene symbol: TTI2
• Synonyms (NCBI Gene): C8orf41, MRT39
• Chromosome: 8
• Chromosome location: 8p12
• Summary: This gene encodes a regulator of the DNA damage response. The protein is a component of the Triple T complex (TTT) which also includes telomere length regulation protein and TELO2 interacting protein 1. The TTT complex is involved in cellular resistance t

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs398122366	G>A,C,T	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029659	hsa-miR-26b-5p	Microarray	19088304
MIRT045214	hsa-miR-186-5p	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005634	Component	Nucleus	NAS	20810650
GO:0050821	Process	Protein stabilization	NAS	20810650
GO:0110078	Component	TTT Hsp90 cochaperone complex	IBA
GO:0110078	Component	TTT Hsp90 cochaperone complex	IEA
GO:0110078	Component	TTT Hsp90 cochaperone complex	IPI	20810650
GO:2000003	Process	Positive regulation of DNA damage checkpoint	NAS	20810650

Other IDs

• MIM: 614426
• HGNC: 26262
• e!Ensembl: ENSG00000129696

Protein

• UniProt ID: Q6NXR4
• Protein name: TELO2-interacting protein 2
• Protein 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 resi
• PDB: 7OLE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10521	Tti2	199 → 447	Tti2 family	Family

• Sequence:

  MELDSALEAPSQEDSNLSEELSHSAFGQAFSKILHCLARPEARRGNVKDAVLKDLGDLIE
  ATEFDRLFEGTGARLRGMPETLGQVAKALEKYAAPSKEEEGGGDGHSEAAEKAAQVGLLF
  LKLLGKVETAKNSLVGPAWQTGLHHLAGPVYIFAITHSLEQPWTTPRSREVAREVLTSLL
  QVTECGSVAGFLHGENEDEKGRLSVILGLLKPDLYKESWKNNPAIKHVFSWTLQQVTRPW
  LSQHLERVLPASLVISDDYQTENKILGVHCLHHIVLNVPAADLLQYNRAQVLYHAISNHL
  YTPEHHLIQAVLLCLLDLFPILEKTLHWKGDGARPTTHCDEVLRLILTHMEPEHRLLLRR
  TYARNLPAFVNRLGILTVRHLKRLERVIIGYLEVYDGPEEEARLKILETLKLLMQHTWPR
  VSCRLVVLLKALLKLICDVARDPNLTPESVKSALLQEATDCLILLDRCSQGRVKGLLAKI
  PQSCEDRKVVNYIRKVQQVSEGAPYNGT

• Sequence length: 508

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome	Likely pathogenic; Pathogenic	rs200045967, rs765235179, rs1180962073, rs1563352011, rs398122366, rs398122367	RCV002463372 RCV003236617 RCV003236618 RCV003990681 RCV000074456 RCV000074457	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 39	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DISABILITY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL RETARDATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE INTELLECTUAL DISABILITY, SHORT STATURE, BEHAVIORAL ABNORMALITIES, FACIAL DYSMORPHISM SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TTI2-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Primary Microcephaly	Primary microcephaly	Pubtator	32061250	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	36724785	Associate	★☆☆☆☆ Found in Text Mining only
Congenital kyphoscoliosis	Congenital kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Deafness Autosomal Recessive 39	Deafness	Pubtator	32061250	Associate	★☆☆☆☆ Found in Text Mining only
Depression Postpartum	Major depressive disorder	Pubtator	36724785	Associate	★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	32061250	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	36724785	Associate	★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	23956177		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	CTD_human_DG	21937992		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual Disability	Mental retardation	BEFREE	23956177, 31290144, 31737043		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual Disability	Intellectual developmental disorder	Pubtator	32061250, 36724785	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual Disability	Mental retardation	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Macrotia	Macrotia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mental deficiency	Mental retardation	CTD_human_DG	21937992		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 39	Mental retardation	ORPHANET_DG	23956177		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 39	Mental retardation	GENOMICS_ENGLAND_DG	23956177		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 39	Mental retardation	UNIPROT_DG	23956177		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 39	Mental retardation	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 39	Mental retardation	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Profound Mental Retardation	Mental retardation	CTD_human_DG	21937992		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome	Intellectual Disability-Short Stature-Behavioral Abnormalities-Facial Dysmorphism Syndrome	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Synophrys	Synophrys	HPO_DG			★☆☆☆☆ Found in Text Mining only