TRAIP

TRAF interacting protein, the group of Ring finger proteins

Basic information

Region (hg38): 3:49828601-49856574

Links

ENSG00000183763

∙ NCBI:10293 ∙ OMIM:605958 ∙ HGNC:30764 ∙ Uniprot:Q9BWF2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Seckel syndrome (Supportive), mode of inheritance: AR
Seckel syndrome 9 (Strong), mode of inheritance: AR
Seckel syndrome 9 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Seckel syndrome 9	AR	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; Pulmonary	26595769

ClinVar

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

not_provided (128 variants)
Inborn_genetic_diseases (55 variants)
Seckel_syndrome_9 (10 variants)
TRAIP-related_disorder (8 variants)
not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAIP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005879.3. 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	35 clinvar	1 clinvar	37
missense	1 clinvar		68 clinvar	9 clinvar		78
nonsense	3 clinvar	1 clinvar	3 clinvar			7
start loss						0
frameshift	6 clinvar		1 clinvar			7
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	10	2	73	44	1

Highest pathogenic variant AF is 0.00008921723

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAIP	protein_coding	protein_coding	ENST00000331456	15	27974

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000159	0.999	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	207	268	0.773	0.0000150	3069
Missense in Polyphen		48	76.122	0.63057		896
Synonymous	1.75	80	103	0.780	0.00000535	903
Loss of Function	2.79	13	29.3	0.443	0.00000151	330

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000644	0.000644
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.00	0.00
South Asian	0.0000981	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin ligase acting as a negative regulator of innate immune signaling. Inhibits activation of NF-kappa-B mediated by TNF. Negatively regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent IFNB1 production and cellular antiviral response by promoting 'Lys-48'-linked polyubiquitination of TNK1 leading to its proteasomal degradation (By similarity) (PubMed:22945920). Involved in response to genotoxic lesions during genome replication. Promotes H2AX and RPA2 phosphorylation after replication-associated DNA damage and assists fork progression at UV-induced replication-blocking lesions during S phase (PubMed:26595769). Has also been proposed to play a role in promoting translesion synthesis by mediating the assembly of 'Lys- 63'-linked poly-ubiquitin chains on the Y-family polymerase POLN in order to facilitate bypass of DNA lesions and preserve genomic integrity (PubMed:24553286). The function in translesion synthesis is controversial (PubMed:26595769). {ECO:0000250|UniProtKB:Q8VIG6, ECO:0000269|PubMed:22945920, ECO:0000269|PubMed:24553286, ECO:0000269|PubMed:26595769, ECO:0000303|PubMed:26595769}.;
Disease: DISEASE: Seckel syndrome 9 (SCKL9) [MIM:616777]: A form of Seckel syndrome, a rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation. {ECO:0000269|PubMed:26595769}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

pRec: 0.0801

Intolerance Scores

loftool: 0.308
rvis_EVS: -0.36
rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

pHI: 0.0760
hipred: Y
hipred_score: 0.661
ghis: 0.602

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.885

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Traip
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); embryo phenotype;

Gene ontology

Biological process: apoptotic process;signal transduction;cell population proliferation;negative regulation of tumor necrosis factor-mediated signaling pathway;protein ubiquitination;negative regulation of NF-kappaB transcription factor activity;negative regulation of interferon-beta production
Cellular component: nucleolus;perinuclear region of cytoplasm
Molecular function: protein binding;metal ion binding;ubiquitin protein ligase activity