TRAF3IP1

TRAF3 interacting protein 1, the group of IFT-B2 complex

Basic information

Region (hg38): 2:238320440-238400897

Links

ENSG00000204104 ∙ NCBI:26146 ∙ OMIM:607380 ∙ HGNC:17861 ∙ Uniprot:Q8TDR0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Senior-Loken syndrome (Supportive), mode of inheritance: AR
• short rib-polydactyly syndrome, Majewski type (Supportive), mode of inheritance: AR
• Senior-Loken syndrome 9 (Strong), mode of inheritance: AR
• Senior-Loken syndrome 9 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Senior-Loken 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	Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	26487268

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAF3IP1 gene.

• not provided (512 variants)
• Inborn genetic diseases (37 variants)
• Senior-Loken syndrome 9 (10 variants)
• not specified (2 variants)
• TRAF3IP1-related condition (1 variants)
• Ellis-van Creveld syndrome (1 variants)
• Short-rib thoracic dysplasia 6 with or without polydactyly (1 variants)
• Jeune thoracic dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAF3IP1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	103	6	110
missense			241	7	6	254
nonsense	5					5
start loss						0
frameshift	13		4			17
inframe indel			4			4
splice donor/acceptor (+/-2bp)		8				8
splice region		1	19	18	3	41
non coding			4	54	25	83
Total	18	8	254	164	37

Highest pathogenic variant AF is 0.0000460

Variants in TRAF3IP1

This is a list of pathogenic ClinVar variants found in the TRAF3IP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-238320563-GC-G			Benign (Jul 14, 2020)
2-238320665-G-T			Uncertain significance (Sep 16, 2018)
2-238320670-C-G			Uncertain significance (Dec 30, 2019)
2-238320680-G-A			Likely benign (Sep 07, 2022)
2-238320684-C-T			Uncertain significance (Nov 08, 2022)
2-238320685-G-A			Uncertain significance (Dec 16, 2021)
2-238320688-C-G			Uncertain significance (Aug 23, 2022)
2-238320688-C-T			Uncertain significance (Apr 18, 2022)
2-238320696-G-T			Uncertain significance (Mar 10, 2022)
2-238320704-G-C			Likely benign (Oct 16, 2023)
2-238320706-A-G			Uncertain significance (Jul 14, 2021)
2-238320713-T-G		Senior-Loken syndrome 9	Pathogenic (Sep 06, 2016)
2-238320714-C-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
2-238320718-G-T			Uncertain significance (Jul 17, 2021)
2-238320719-G-T			Uncertain significance (Jul 27, 2022)
2-238320730-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
2-238320730-CC-TA			Uncertain significance (Jun 13, 2022)
2-238320731-C-A		Senior-Loken syndrome 9	Benign (Jan 31, 2024)
2-238320731-C-G			Likely benign (Dec 13, 2023)
2-238320750-C-T		Senior-Loken syndrome 9	Uncertain significance (Mar 19, 2022)
2-238320751-C-T			Uncertain significance (Jan 11, 2022)
2-238320752-C-G			Likely benign (Jul 19, 2022)
2-238320755-G-A			Likely benign (Oct 22, 2023)
2-238320758-C-T			Likely benign (Nov 18, 2023)
2-238320763-A-G			Uncertain significance (May 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAF3IP1	protein_coding	protein_coding	ENST00000373327	17	80460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.91e-8	0.998	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.328	346	364	0.952	0.0000205	4507
Missense in Polyphen		73	95.424	0.76501		1202
Synonymous	-0.297	145	141	1.03	0.00000869	1250
Loss of Function	2.83	19	37.8	0.503	0.00000206	491

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000319	0.000312
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000166	0.000163
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000234	0.000229
Middle Eastern	0.000166	0.000163
South Asian	0.000266	0.000261
Other	0.000335	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an inhibitory role on IL13 signaling by binding to IL13RA1. Involved in suppression of IL13-induced STAT6 phosphorylation, transcriptional activity and DNA-binding. Recruits TRAF3 and DISC1 to the microtubules. Involved in kidney development and epithelial morphogenesis. Involved in the regulation of microtubule cytoskeleton organization. Is a negative regulator of microtubule stability, acting through the control of MAP4 levels (PubMed:26487268). Involved in ciliogenesis (By similarity). {ECO:0000250|UniProtKB:Q149C2, ECO:0000269|PubMed:10791955, ECO:0000269|PubMed:12812986, ECO:0000269|PubMed:12935900, ECO:0000269|PubMed:26487268}.
• Pathway: Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• loftool: 0.907
• rvis_EVS: 0.96
• rvis_percentile_EVS: 90.17

Haploinsufficiency Scores

• pHI: 0.129
• hipred: N
• hipred_score: 0.473
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.407

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Traf3ip1
• Phenotype: homeostasis/metabolism phenotype; cellular 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); limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: traf3ip1
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: morphogenesis of a polarized epithelium;kidney development;negative regulation of protein phosphorylation;neural tube patterning;embryonic camera-type eye development;negative regulation of protein complex assembly;negative regulation of type I interferon production;negative regulation of interferon-beta production;embryonic heart tube development;intraciliary transport involved in cilium assembly;post-anal tail morphogenesis;intraciliary transport;embryonic digit morphogenesis;negative regulation of defense response to virus;regulation of microtubule cytoskeleton organization;negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning
• Cellular component: centrosome;cilium;axoneme;intraciliary transport particle B;ciliary transition zone;ciliary basal body;ciliary tip;ciliary base
• Molecular function: protein binding;microtubule binding