TBX18

protein-coding

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

Gene summary

This genes codes for a member of an evolutionarily conserved family of transcription factors that plays a crucial role in embryonic development. The family is characterized by the presence of the DNA-binding T-box domain and is divided into five sub-families based on sequence conservation in this domain. The encoded protein belongs to the vertebrate specific Tbx1 sub-family. The protein acts as a transcriptional repressor by antagonizing transcriptional activators in the T-box family. The protein forms homo- or heterodimers with other transcription factors of the T-box family or other transcription factors. [provided by RefSeq, Nov 2012]

MANE transcript

NM_001080508.3

Inheritance

ClinVar variants

P:7U:154B:61

Top phenotype

Congenital anomalies of the kidney and urinary tract 2

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr6:84,687,351-84,764,598

External References & Databases

Ensembl (ENSG00000112837)

Transcript & Mutation Effects

hg38 • Region Span ~77.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital anomalies of kidney and urinary tract 2LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0027676

Submitter: Labcorp Genetics (formerly Invitae)

congenital anomalies of kidney and urinary tract 2MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0027676

Submitter: Ambry Genetics

congenital anomalies of kidney and urinary tract 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0027676

Submitter: PanelApp Australia

congenital anomalies of kidney and urinary tract 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0027676

Submitter: G2P

Clinical Genomic Database (CGD)

Congenital anomalies of the kidney and urinary tract 2AD

Manifestation: Renal

Intervention: Renal

Rationale: Monitoring and intervention related to vesicoureteral reflux may be beneficial in terms of helping to preserve renal function

Comments: Renal transplantation has been described

Refs: 26235987

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TBX18 variants in ClinVar

10 Conditions Cataloged

not providedTotal: 152

Inborn genetic diseasesTotal: 72

Congenital anomalies of kidney and urinary tract 2Total: 23

TBX18-related disorderTotal: 17

not specifiedTotal: 3

Congenital anomaly of kidney and urinary tractTotal: 2

Incidental DiscoveryTotal: 1

Chronic kidney diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080508.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	43 clinvar	4 clinvar	48
missense	1 clinvar	1 clinvar	143 clinvar	13 clinvar	1 clinvar	159
nonsense	1 clinvar	2 clinvar	1 clinvar			4
start loss						0
frameshift	1 clinvar	1 clinvar	2 clinvar			4
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	3	4	154	56	5	222

Highest pathogenic variant AF is 0.000008853374

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080508.3	RefSeq	NP_001073977.1	8	MANE Select
ENST00000369663.10	Ensembl	ENSP00000358677.4	8	MANE Select
ENST00000606325.5	Ensembl	ENSP00000475498.1	5	Standard
ENST00000606621.1	Ensembl	ENSP00000476137.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369663
Coding exons: 8
Length: 77169
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125721
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0990	336	341	0.985	0.0000177	3881
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.247

Gene Damage Prediction

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