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.

not_provided (276 variants)
not_specified (178 variants)
TRAP1-related_disorder (34 variants)
Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
Hereditary_renal_cell_carcinoma (1 variants)
HER2_positive_breast_carcinoma (1 variants)
VATER_association (1 variants)
Congenital_anomalies_of_kidney_and_urinary_tract_1 (1 variants)

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. These statistics are base on transcript: NM_000016292.3. 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				61 clinvar	4 clinvar	65
missense			242 clinvar	19 clinvar	7 clinvar	268
nonsense	1 clinvar		4 clinvar			5
start loss			2			2
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	0	259	80	11

Highest pathogenic variant AF is 6.85546e-7

Loading clinvar variants...

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