TBX18

T-box transcription factor 18, the group of T-box transcription factors

Basic information

Region (hg38): 6:84687351-84764598

Links

ENSG00000112837 ∙ NCBI:9096 ∙ OMIM:604613 ∙ HGNC:11595 ∙ Uniprot:O95935 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital anomalies of kidney and urinary tract 2 (Limited), mode of inheritance: Unknown
• congenital anomalies of kidney and urinary tract 2 (Strong), mode of inheritance: AD
• congenital anomalies of kidney and urinary tract 2 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital anomalies of the kidney and urinary tract 2	AD	Renal	Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function	Renal	26235987
Renal transplantation has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBX18 gene.

• Congenital anomalies of kidney and urinary tract 2 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBX18 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				27	4	31
missense			64	8	3	75
nonsense	1					1
start loss						0
frameshift	1		1			2
inframe indel			2		1	3
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding				10	13	23
Total	2	0	67	45	21

Variants in TBX18

This is a list of pathogenic ClinVar variants found in the TBX18 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-84736692-A-G		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
6-84736693-T-C		Inborn genetic diseases	Uncertain significance (Dec 15, 2022)
6-84736696-G-A			Uncertain significance (Oct 03, 2022)
6-84736707-T-C		Congenital anomaly of kidney and urinary tract	Likely pathogenic (Aug 24, 2018)
6-84736735-G-A			Likely benign (Jun 29, 2023)
6-84736735-G-C			Uncertain significance (Nov 14, 2023)
6-84736768-C-A			Uncertain significance (Nov 08, 2022)
6-84736770-C-G		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
6-84736801-G-A			Uncertain significance (Jan 02, 2024)
6-84736808-C-G			Uncertain significance (Mar 01, 2023)
6-84736812-C-T			Uncertain significance (Mar 08, 2023)
6-84736832-C-T			Likely benign (Oct 11, 2023)
6-84736848-A-G			Uncertain significance (Sep 06, 2022)
6-84736884-G-A		TBX18-related disorder	Uncertain significance (Oct 08, 2022)
6-84736899-G-C		Inborn genetic diseases	Uncertain significance (Aug 18, 2023)
6-84736916-T-A			Likely benign (Dec 26, 2023)
6-84736931-G-T			Likely benign (Jun 13, 2023)
6-84736939-G-A		Congenital anomalies of kidney and urinary tract 2	Pathogenic (Aug 06, 2015)
6-84736951-T-C		Inborn genetic diseases	Uncertain significance (Jan 15, 2024)
6-84736953-T-C		Inborn genetic diseases	Uncertain significance (Mar 15, 2023)
6-84736963-C-T			Uncertain significance (Jun 30, 2023)
6-84736983-G-A		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
6-84736985-G-A			Likely benign (Oct 24, 2023)
6-84737026-G-T			Uncertain significance (Dec 03, 2021)
6-84737030-G-A			Likely benign (May 29, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBX18	protein_coding	protein_coding	ENST00000369663	8	77169

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000950	125718	0	3	125721	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0990	336	341	0.985	0.0000177	3881
Missense in Polyphen		137	163.74	0.8367		1852
Synonymous	1.37	123	144	0.855	0.00000803	1282
Loss of Function	4.41	1	24.6	0.0407	0.00000138	272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000882	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as transcriptional repressor involved in developmental processes of a variety of tissues and organs, including the heart and coronary vessels, the ureter and the vertebral column. Required for embryonic development of the sino atrial node (SAN) head area. {ECO:0000250|UniProtKB:Q9EPZ6, ECO:0000269|PubMed:26235987}.
• Disease: DISEASE: Congenital anomalies of kidney and urinary tract 2 (CAKUT2) [MIM:143400]: A disorder encompassing a broad spectrum of renal and urinary tract malformations that include renal agenesis, kidney hypodysplasia, multicystic kidney dysplasia, duplex collecting system, posterior urethral valves and ureter abnormalities. Congenital anomalies of kidney and urinary tract are the commonest cause of chronic kidney disease in children. {ECO:0000269|PubMed:26235987}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.0155
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.394
• hipred: Y
• hipred_score: 0.783
• ghis: 0.573

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.247

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbx18
• 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); growth/size/body region phenotype; cellular phenotype; muscle phenotype; craniofacial 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; respiratory system phenotype; skeleton phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;negative regulation of canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation;renal system development
• Cellular component: nucleus
• Molecular function: transcription regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;protein binding;protein homodimerization activity;protein heterodimerization activity