TRAP1

TNF receptor associated protein 1, the group of Heat shock 90kDa proteins

Basic information

Region (hg38): 16:3651639-3717553

Links

ENSG00000126602 ∙ NCBI:10131 ∙ OMIM:606219 ∙ HGNC:16264 ∙ Uniprot:Q12931 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital abnormalities of the kidney and urinary tract; VACTERL association	AR	Cardiovascular; Renal	The condition can involve congenital cardiac anomalies, and awareness may allow early management; Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function	Cardiovascular; Gastrointestinal; Genitourinary; Musculoskeletal; Renal	24152966

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAP1 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	48	6	55
missense			144	13	9	166
nonsense			2			2
start loss			1		1	2
frameshift						0
inframe indel					2	2
splice donor/acceptor (+/-2bp)			4			4
splice region			3	13	6	22
non coding			2	19	30	51
Total	0	0	154	80	48

Variants in TRAP1

This is a list of pathogenic ClinVar variants found in the TRAP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-3655386-A-T		Systemic lupus erythematosus, susceptibility to	risk factor (Aug 01, 2001)
16-3655426-A-C		not specified	Uncertain significance (Nov 05, 2021)
16-3655434-G-A		not specified	Uncertain significance (Apr 26, 2024)
16-3655453-C-T			Uncertain significance (Jul 06, 2021)
16-3655464-C-T		Systemic lupus erythematosus	Likely pathogenic (Apr 04, 2024)
16-3655478-G-C			Likely benign (Jul 01, 2024)
16-3655492-A-G		not specified	Uncertain significance (Mar 31, 2022)
16-3655499-C-T		DNASE1-related disorder	Likely benign (Dec 05, 2019)
16-3655869-C-T		DNASE1-related disorder	Likely benign (Jun 05, 2019)
16-3655934-A-C		DNASE1-related disorder	Uncertain significance (Apr 26, 2024)
16-3656145-G-C		not specified	Uncertain significance (Sep 20, 2022)
16-3656165-G-A			Likely benign (Dec 01, 2023)
16-3656184-A-G			Benign (Sep 01, 2022)
16-3656642-G-C		not specified	Uncertain significance (Apr 18, 2023)
16-3656667-A-C			Benign (May 01, 2024)
16-3656695-C-T		DNASE1-related disorder	Likely benign (Apr 25, 2019)
16-3656696-G-A		Systemic lupus erythematosus	Benign (-)
16-3656702-G-A		Systemic lupus erythematosus	Uncertain significance (Jun 09, 2022)
16-3656715-G-A		Systemic lupus erythematosus	Uncertain significance (Mar 26, 2024)
16-3656727-T-C			Uncertain significance (Aug 14, 2023)
16-3656979-C-T			Uncertain significance (May 01, 2020)
16-3657001-G-A			Likely benign (Mar 01, 2022)
16-3657015-C-T			Likely benign (May 01, 2024)
16-3657022-C-G		DNASE1-related disorder	Benign (Jan 14, 2020)
16-3657063-C-T		DNASE1-related disorder	Likely benign (Jan 02, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAP1	protein_coding	protein_coding	ENST00000246957	18	65959

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.60e-29	0.0000193	125557	0	191	125748	0.000760

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.72	587	428	1.37	0.0000283	4533
Missense in Polyphen		257	185.01	1.3891		1868
Synonymous	-4.33	255	181	1.41	0.0000129	1397
Loss of Function	-0.526	42	38.5	1.09	0.00000205	439

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00224	0.00218
Ashkenazi Jewish	0.00	0.00
East Asian	0.000655	0.000653
Finnish	0.000237	0.000231
European (Non-Finnish)	0.000783	0.000756
Middle Eastern	0.000655	0.000653
South Asian	0.00138	0.00137
Other	0.000182	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA. {ECO:0000269|PubMed:23525905, ECO:0000269|PubMed:23564345, ECO:0000269|PubMed:23747254}.
• Pathway: TNF alpha Signaling Pathway;TGF-beta Signaling Pathway;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TGF_beta_Receptor;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.927
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.08

Haploinsufficiency Scores

• pHI: 0.387
• hipred: N
• hipred_score: 0.498
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.819

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trap1
• Phenotype: liver/biliary system phenotype; hematopoietic system phenotype; neoplasm; immune system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: translational attenuation;chaperone-mediated protein folding;negative regulation of cellular respiration;negative regulation of reactive oxygen species biosynthetic process;negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
• Cellular component: nucleoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial intermembrane space;mitochondrial matrix;membrane
• Molecular function: RNA binding;tumor necrosis factor receptor binding;protein binding;ATP binding;protein kinase binding;unfolded protein binding