TRIP12

thyroid hormone receptor interactor 12, the group of HECT domain containing|Armadillo like helical domain containing

Basic information

Region (hg38): 2:229763837-229923239

Links

ENSG00000153827

∙ NCBI:9320 ∙ OMIM:604506 ∙ HGNC:12306 ∙ Uniprot:Q14669 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Clark-Baraitser syndrome (Strong), mode of inheritance: AD
syndromic intellectual disability (Supportive), mode of inheritance: AD
complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
Clark-Baraitser syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Clark-Baraitser syndrome	AD	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; Musculoskeletal; Neurologic	25363768; 27479843; 27848077; 28251352

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIP12 gene.

not_provided (263 variants)
Inborn_genetic_diseases (137 variants)
Clark-Baraitser_syndrome (121 variants)
TRIP12-related_disorder (41 variants)
not_specified (18 variants)
Intellectual_disability (8 variants)
See_cases (6 variants)
Neurodevelopmental_disorder (4 variants)
Developmental_disorder (2 variants)
TRIP12_associated_autism_with_facial_dysmorphology (1 variants)
Self-limited_familial_infantile_epilepsy (1 variants)
Neurodevelopmental_delay (1 variants)
Prostate_cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIP12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001348323.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	32 clinvar	5 clinvar	38
missense	3 clinvar	12 clinvar	326 clinvar	40 clinvar		381
nonsense	17 clinvar	10 clinvar	2 clinvar			29
start loss						0
frameshift	33 clinvar	13 clinvar	3 clinvar			49
splice donor/acceptor (+/-2bp)	9 clinvar	3 clinvar	3 clinvar			15
Total	62	38	335	72	5

Highest pathogenic variant AF is 0.0000336963

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIP12	protein_coding	protein_coding	ENST00000283943	40	159402

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.52e-16	125733	0	7	125740	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.64	639	1.07e+3	0.600	0.0000566	12993
Missense in Polyphen		153	406.33	0.37654		4969
Synonymous	-0.763	402	383	1.05	0.0000205	3863
Loss of Function	9.34	2	106	0.0190	0.00000569	1297

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000613	0.0000613
Ashkenazi Jewish	0.00	0.00
East Asian	0.000112	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000179	0.0000176
Middle Eastern	0.000112	0.0000544
South Asian	0.0000677	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardeless of the presence of lysine residues in target proteins. In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692}.;
Disease: DISEASE: Mental retardation, autosomal dominant 49 (MRD49) [MIM:617752]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:27848077, ECO:0000269|PubMed:28251352}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

pRec: 0.104

Intolerance Scores

loftool: 0.0453
rvis_EVS: -2.46
rvis_percentile_EVS: 1

Haploinsufficiency Scores

pHI: 0.887
hipred: Y
hipred_score: 0.783
ghis: 0.621

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.630

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Trip12
Phenotype: cellular phenotype; growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype;

Gene ontology

Biological process: protein polyubiquitination;DNA repair;ubiquitin-dependent protein catabolic process;cellular response to DNA damage stimulus;regulation of embryonic development;negative regulation of histone H2A K63-linked ubiquitination;negative regulation of double-strand break repair
Cellular component: nucleus;nucleoplasm;cytosol;nuclear speck
Molecular function: ubiquitin-protein transferase activity;protein binding;thyroid hormone receptor binding