TMPO

thymopoietin, the group of LEM domain containing

Basic information

Region (hg38): 12:98515578-98550351

Links

ENSG00000120802 ∙ NCBI:7112 ∙ OMIM:188380 ∙ HGNC:11875 ∙ Uniprot:P42166, P42167 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• dilated cardiomyopathy (Refuted Evidence), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Refuted Evidence), mode of inheritance: AD
• hypertrophic cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1T	AD	Cardiovascular	Preventive measures, surveillance (eg, including echocardiography/electrocardiography), and medical management may be helpful to help decrease morbidity	Cardiovascular	16247757
The onset of symptoms has been described in adults, but surveillance and medical management may be beneficial prior to adulthood

ClinVar

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

• Loeys-Dietz syndrome 2 (360 variants)
• Inborn genetic diseases (256 variants)
• not provided (163 variants)
• not specified (81 variants)
• Dilated cardiomyopathy 1T (6 variants)
• Primary dilated cardiomyopathy (5 variants)
• Cardiomyopathy (4 variants)
• Primary familial hypertrophic cardiomyopathy (3 variants)
• Long QT syndrome (3 variants)
• Cardiovascular phenotype (3 variants)
• TMPO-related condition (2 variants)
• Hypertrophic cardiomyopathy (2 variants)
• Arrhythmogenic right ventricular cardiomyopathy (1 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• Dilated Cardiomyopathy, Dominant (1 variants)
• Hypertrophic cardiomyopathy 25 (1 variants)
• Arrhythmogenic right ventricular cardiomyopathy;Amyloidosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMPO 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				158	3	161
missense			299	11	10	320
nonsense			11			11
start loss						0
frameshift			14			14
inframe indel			6			6
splice donor/acceptor (+/-2bp)						0
splice region			4	4	2	10
non coding			6	25	26	57
Total	0	0	336	194	39

Variants in TMPO

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

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

Position	Type	Phenotype	Significance	ClinVar
12-98515742-A-T		Dilated Cardiomyopathy, Dominant	Uncertain significance (Jun 14, 2016)
12-98515857-A-C		not specified	Benign/Likely benign (Oct 19, 2020)
12-98515866-A-T			Uncertain significance (Jul 13, 2023)
12-98515867-G-C		not specified	Uncertain significance (Feb 15, 2018)
12-98515872-C-T		Loeys-Dietz syndrome 2	Uncertain significance (Dec 25, 2021)
12-98515880-C-T		Loeys-Dietz syndrome 2 • not specified	Benign/Likely benign (Feb 11, 2023)
12-98515886-G-C		not specified	Uncertain significance (Apr 17, 2023)
12-98515891-C-T		Cardiovascular phenotype	Likely benign (Dec 10, 2012)
12-98515893-C-T		not specified	Uncertain significance (Apr 18, 2023)
12-98515903-A-G		Loeys-Dietz syndrome 2 • not specified	Likely benign (Jan 09, 2024)
12-98515913-T-C		not specified	Likely benign (May 09, 2022)
12-98515915-G-A		Loeys-Dietz syndrome 2	Likely benign (Dec 15, 2020)
12-98515918-G-A		Loeys-Dietz syndrome 2 • not specified	Likely benign (Jan 13, 2024)
12-98515919-A-G		Loeys-Dietz syndrome 2	Uncertain significance (Jan 08, 2021)
12-98515921-T-G		not specified	Uncertain significance (Jan 27, 2024)
12-98515930-C-A		Loeys-Dietz syndrome 2	Likely benign (May 31, 2022)
12-98515933-C-T		Loeys-Dietz syndrome 2	Likely benign (Nov 26, 2021)
12-98515937-A-C		not specified • Loeys-Dietz syndrome 2	Uncertain significance (Oct 03, 2023)
12-98515939-T-C		not specified • Loeys-Dietz syndrome 2	Likely benign (Sep 15, 2021)
12-98515939-T-G		not specified	Uncertain significance (Dec 25, 2023)
12-98515944-C-G		not specified	Uncertain significance (Jul 27, 2023)
12-98515944-C-T		not specified	Uncertain significance (Mar 08, 2013)
12-98515946-C-CT			Uncertain significance (Jan 17, 2023)
12-98515948-G-T		Loeys-Dietz syndrome 2	Benign (Jul 29, 2022)
12-98515951-G-A		Loeys-Dietz syndrome 2 • not specified	Likely benign (Jan 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMPO	protein_coding	protein_coding	ENST00000266732	4	34868

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.55e-7	0.851	125668	1	79	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.608	383	351	1.09	0.0000166	4463
Missense in Polyphen		118	126.14	0.9355		1605
Synonymous	-3.17	189	141	1.34	0.00000699	1444
Loss of Function	1.54	14	21.8	0.643	9.98e-7	302

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00106	0.00106
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000381	0.000381
Finnish	0.000466	0.000462
European (Non-Finnish)	0.000212	0.000211
Middle Eastern	0.000381	0.000381
South Asian	0.000294	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly. Plays an important role, together with LMNA, in the nuclear anchorage of RB1.
• Pathway: Clearance of Nuclear Envelope Membranes from Chromatin;Nuclear Envelope Breakdown;Mitotic Prophase;Initiation of Nuclear Envelope Reformation;Nuclear Envelope Reassembly;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.427

Intolerance Scores

• loftool: 0.760
• rvis_EVS: 1.52
• rvis_percentile_EVS: 95.48

Haploinsufficiency Scores

• pHI: 0.672
• hipred: N
• hipred_score: 0.396
• ghis: 0.638

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmpo
• Phenotype: digestive/alimentary phenotype; limbs/digits/tail phenotype; hematopoietic system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of transcription, DNA-templated
• Cellular component: chromatin;nucleus;nuclear envelope
• Molecular function: DNA binding;protein binding;lamin binding;cadherin binding