TPR

translocated promoter region, nuclear basket protein, the group of Nucleoporins

Basic information

Region (hg38): 1:186311652-186375693

Links

ENSG00000047410 ∙ NCBI:7175 ∙ OMIM:189940 ∙ HGNC:12017 ∙ Uniprot:P12270 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal recessive 79 (Limited), mode of inheritance: Unknown
• intellectual developmental disorder, autosomal recessive 79 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 79	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; Ophthalmologic	34494102

ClinVar

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

• not provided (2 variants)
• Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPR 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				7	2	9
missense			76	6	2	84
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding	3	2	5	4	1	15
Total	3	2	81	17	5

Variants in TPR

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

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

Position	Type	Phenotype	Significance	ClinVar
1-186312194-T-C		PRG4-related disorder	Likely benign (Apr 30, 2019)
1-186312227-TG-T			Pathogenic (Nov 01, 2022)
1-186312229-GA-G			Pathogenic (Apr 19, 2022)
1-186312260-T-C			Benign/Likely benign (Oct 01, 2023)
1-186312268-C-T		PRG4-related disorder	Benign (Apr 12, 2019)
1-186312284-ACGTCG-A		Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	Likely pathogenic (Sep 22, 2024)
1-186312295-A-G		Inborn genetic diseases	Uncertain significance (Jan 31, 2023)
1-186312296-ACGTGCTATAGGACCTTCT-A		Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	Pathogenic (Feb 04, 2018)
1-186312345-C-T		Inborn genetic diseases	Uncertain significance (Sep 26, 2022)
1-186312788-TAA-T			Likely pathogenic (Nov 01, 2020)
1-186312792-G-A		Inborn genetic diseases	Uncertain significance (Jul 26, 2021)
1-186312806-G-A		Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	Likely pathogenic (-)
1-186312811-G-T		Inborn genetic diseases	Uncertain significance (Oct 22, 2021)
1-186312841-C-G		Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	Pathogenic (Nov 24, 2019)
1-186312866-C-T			Likely benign (Oct 01, 2022)
1-186312878-C-G		Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	Pathogenic (Feb 04, 2018)
1-186312884-C-A			Benign/Likely benign (Dec 01, 2022)
1-186313690-A-G		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
1-186313753-CC-AG		Camptodactyly-arthropathy-coxa vara-pericarditis syndrome	Pathogenic (Nov 01, 1999)
1-186314718-C-T		not specified	Uncertain significance (Dec 20, 2023)
1-186317520-G-A		not specified	Uncertain significance (Oct 14, 2023)
1-186318508-T-C		not specified	Uncertain significance (May 23, 2023)
1-186318558-G-C		not specified	Uncertain significance (Feb 06, 2023)
1-186318771-C-T		not specified	Uncertain significance (Apr 13, 2022)
1-186318772-G-A		Intellectual developmental disorder, autosomal recessive 79	Pathogenic (May 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPR	protein_coding	protein_coding	ENST00000367478	51	64042

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.90e-17	124884	0	20	124904	0.0000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.99	900	1.19e+3	0.756	0.0000627	15498
Missense in Polyphen		21	50.762	0.41369		517
Synonymous	-0.941	425	401	1.06	0.0000193	4365
Loss of Function	10.3	9	141	0.0638	0.00000758	1694

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000290	0.000288
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000463
European (Non-Finnish)	0.000107	0.000106
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:22253824 and PubMed:11952838). Plays also a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases. {ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:15654337, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:20407419, ECO:0000269|PubMed:21613532, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:9864356}.
• Disease: DISEASE: Note=A chromosomal aberration involving TPR has been found in papillary thyroid carcinomas (PTCs). Intrachromosomal rearrangement that links the 5'-end of the TPR gene to the protein kinase domain of NTRK1 forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the carboxy terminus of the NTRK1 protein. {ECO:0000269|PubMed:1532241}.; DISEASE: Note=Involved in tumorigenic rearrangements with the MET. {ECO:0000269|PubMed:2300559}.
• Pathway: RNA transport - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);tRNA processing;Disease;Gene expression (Transcription);Regulation of HSF1-mediated heat shock response;Metabolism of carbohydrates;Rev-mediated nuclear export of HIV RNA;Late Phase of HIV Life Cycle;HIV Life Cycle;Interactions of Rev with host cellular proteins;Host Interactions of HIV factors;HIV Infection;snRNP Assembly;Vpr-mediated nuclear import of PICs;SUMOylation of DNA damage response and repair proteins;Transport of Ribonucleoproteins into the Host Nucleus;Viral Messenger RNA Synthesis;Export of Viral Ribonucleoproteins from Nucleus;SUMOylation of chromatin organization proteins;Influenza Viral RNA Transcription and Replication;Cellular responses to stress;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;NEP/NS2 Interacts with the Cellular Export Machinery;Metabolism of proteins;Influenza Life Cycle;Influenza Infection;Metabolism of RNA;Infectious disease;Metabolism;Transport of the SLBP independent Mature mRNA;Transport of the SLBP Dependant Mature mRNA;Transport of Mature mRNA Derived from an Intronless Transcript;Transport of Mature mRNAs Derived from Intronless Transcripts;SUMOylation;Cellular responses to external stimuli;Regulation of Glucokinase by Glucokinase Regulatory Protein;Glycolysis;Nuclear Pore Complex (NPC) Disassembly;tRNA processing in the nucleus;Transport of Mature mRNA derived from an Intron-Containing Transcript;Metabolism of non-coding RNA;Cellular response to heat stress;Nuclear Envelope Breakdown;Mitotic Prophase;M Phase;Nuclear import of Rev protein;Glucose metabolism;Transcriptional regulation by small RNAs;Cell Cycle;Interactions of Vpr with host cellular proteins;Cell Cycle, Mitotic;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA;Gene Silencing by RNA (Consensus)

Intolerance Scores

• loftool: 0.361
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.05

Haploinsufficiency Scores

• pHI: 0.945
• hipred: Y
• hipred_score: 0.736
• ghis: 0.627

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.952

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tpr
• 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)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;RNA import into nucleus;RNA export from nucleus;mRNA export from nucleus;protein import into nucleus;protein export from nucleus;nuclear pore organization;mitotic spindle assembly checkpoint;regulation of mRNA export from nucleus;regulation of mitotic sister chromatid separation;viral process;positive regulation of heterochromatin assembly;regulation of protein stability;mRNA export from nucleus in response to heat stress;regulation of protein localization;cellular response to heat;cellular response to interferon-alpha;regulation of protein import into nucleus;positive regulation of protein import into nucleus;nuclear matrix organization;negative regulation of translational initiation;regulation of protein export from nucleus;positive regulation of protein export from nucleus;negative regulation of RNA export from nucleus;nuclear pore complex assembly;cell division;response to epidermal growth factor;positive regulation of mitotic cell cycle spindle assembly checkpoint;positive regulation of intracellular protein transport;regulation of mitotic spindle assembly
• Cellular component: kinetochore;nucleus;nuclear envelope;nuclear pore;nucleoplasm;cytoplasm;cytoplasmic dynein complex;extrinsic component of membrane;nuclear membrane;nuclear periphery;nuclear inclusion body;nuclear pore nuclear basket;mitotic spindle
• Molecular function: chromatin binding;RNA binding;mRNA binding;transporter activity;protein binding;tubulin binding;structural constituent of nuclear pore;heat shock protein binding;protein homodimerization activity;protein membrane anchor;mitogen-activated protein kinase binding;dynein complex binding