TRAF7

TNF receptor associated factor 7, the group of TNF receptor associated factors|Ring finger proteins|Zinc fingers TRAF-type|WD repeat domain containing

Basic information

Region (hg38): 16:2155698-2178129

Previous symbols: [ "RFWD1" ]

Links

ENSG00000131653 ∙ NCBI:84231 ∙ OMIM:606692 ∙ HGNC:20456 ∙ Uniprot:Q6Q0C0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardiac, facial, and digital anomalies with developmental delay (Definitive), mode of inheritance: AD
• cardiac, facial, and digital anomalies with developmental delay (Strong), mode of inheritance: AD
• cardiac, facial, and digital anomalies with developmental delay (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiac, facial, and digital anomalies with developmental delay	AD	Cardiovascular	Among other findings, individuals have been described with heart anomalies (eg, including structural anomalies and arrthymia), and awareness may allow prompt diagnosis and management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	25961944; 29961569

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAF7 gene.

• not provided (3 variants)
• Cardiac, facial, and digital anomalies with developmental delay (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAF7 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				17	1	18
missense	3	8	70	12		93
nonsense			3			3
start loss			1			1
frameshift			3			3
inframe indel					1	1
splice donor/acceptor (+/-2bp)			3			3
splice region			3	2	2	7
non coding				1	1	2
Total	3	8	80	30	3

Variants in TRAF7

This is a list of pathogenic ClinVar variants found in the TRAF7 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-2163921-A-G			Uncertain significance (May 25, 2022)
16-2163934-A-G		not specified	Uncertain significance (Apr 23, 2024)
16-2163935-G-C		Inborn genetic diseases	Likely benign (Sep 29, 2022)
16-2163951-C-T		Inborn genetic diseases	Likely benign (May 10, 2022)
16-2163952-G-A		Inborn genetic diseases	Likely benign (Oct 13, 2023)
16-2163976-T-C		not specified	Uncertain significance (Oct 12, 2022)
16-2163979-CCACCCCAGACGT-C		TRAF7-related disorder	Benign (Jul 01, 2024)
16-2163985-C-A		not specified	Uncertain significance (Aug 09, 2023)
16-2163985-C-T		Inborn genetic diseases	Likely benign (Jan 29, 2025)
16-2164005-AGGGTGTGCC-A		TRAF7-related disorder	Benign (Jul 31, 2018)
16-2165906-G-A		Inborn genetic diseases	Likely benign (May 24, 2023)
16-2165918-G-A		Inborn genetic diseases	Uncertain significance (Nov 09, 2022)
16-2165932-A-G			Likely benign (Mar 01, 2024)
16-2165942-C-T		Inborn genetic diseases	Likely benign (Aug 03, 2023)
16-2168089-G-A		Inborn genetic diseases	Likely benign (Oct 01, 2024)
16-2168096-C-A		not specified	Uncertain significance (May 04, 2022)
16-2168097-A-C		Cardiac, facial, and digital anomalies with developmental delay	Uncertain significance (May 09, 2024)
16-2168115-C-T		Cardiac, facial, and digital anomalies with developmental delay	Uncertain significance (-)
16-2168137-C-G		Inborn genetic diseases • TRAF7-related disorder	Likely benign (Oct 27, 2021)
16-2168142-T-C		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
16-2168146-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 01, 2024)
16-2168147-G-A		Inborn genetic diseases	Likely benign (Jul 09, 2024)
16-2170618-C-G			Uncertain significance (Dec 19, 2023)
16-2170620-A-G		Cardiac, facial, and digital anomalies with developmental delay	Uncertain significance (Nov 16, 2021)
16-2170626-A-G		not specified	Uncertain significance (Feb 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAF7	protein_coding	protein_coding	ENST00000326181	20	22432

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0218	0.978	125719	0	23	125742	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.26	248	441	0.563	0.0000289	4385
Missense in Polyphen		40	130.65	0.30616		1396
Synonymous	-1.53	215	188	1.14	0.0000140	1281
Loss of Function	4.24	11	39.9	0.276	0.00000197	432

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000121	0.000120
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000478	0.0000462
European (Non-Finnish)	0.0000991	0.0000967
Middle Eastern	0.000163	0.000163
South Asian	0.0000984	0.0000980
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin ligase capable of auto-ubiquitination, following phosphorylation by MAP3K3. Potentiates MEKK3-mediated activation of the NF-kappa-B, JUN/AP1 and DDIT3 transcriptional regulators. Induces apoptosis when overexpressed. {ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:15001576}.
• Pathway: Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;TNFalpha (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.468
• rvis_EVS: -1.51
• rvis_percentile_EVS: 3.5

Haploinsufficiency Scores

• pHI: 0.166
• hipred: Y
• hipred_score: 0.790
• ghis: 0.680

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.961

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Traf7

Gene ontology

• Biological process: ribosomal large subunit assembly;activation of MAPKKK activity;apoptotic process;Notch signaling pathway;protein ubiquitination;positive regulation of MAPK cascade;positive regulation of apoptotic signaling pathway
• Cellular component: ubiquitin ligase complex;nucleolus;plasma membrane;cytoplasmic vesicle;intracellular membrane-bounded organelle
• Molecular function: ubiquitin-protein transferase activity;protein binding;zinc ion binding