TBX15

protein-coding

T-box transcription factor 15, the group of T-box transcription factors

Gene summary

This gene belongs to the T-box family of genes, which encode a phylogenetically conserved family of transcription factors that regulate a variety of developmental processes. All these genes contain a common T-box DNA-binding domain. Mutations in this gene are associated with Cousin syndrome.[provided by RefSeq, Oct 2009]

Previous symbols:

TBX14

MANE transcript

NM_001330677.2

Inheritance

ClinVar variants

P:4U:103B:60

Top phenotype

Cousin syndrome

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr1:118,883,046-118,989,556

External References & Databases

Ensembl (ENSG00000092607)

Transcript & Mutation Effects

hg38 • Region Span ~106.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pelviscapular dysplasiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009845

Submitter: Orphanet

pelviscapular dysplasiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009845

Submitter: G2P

pelviscapular dysplasiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009845

Submitter: Labcorp Genetics (formerly Invitae)

pelviscapular dysplasiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009845

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Cousin syndromeAR

Manifestation: Craniofacial; Musculoskeletal

Intervention: General

Rationale: 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

Refs: 7103674; 19068278

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TBX15 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 153

Inborn genetic diseasesTotal: 61

Pelviscapular dysplasiaTotal: 17

TBX15-related disorderTotal: 10

not specifiedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001330677.2. 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				52 clinvar	2 clinvar	54
missense			99 clinvar	5 clinvar	1 clinvar	105
nonsense	1 clinvar		2 clinvar			3
start loss						0
frameshift	2 clinvar	1 clinvar	2 clinvar			5
splice donor/acceptor (+/-2bp)						0
Total	3	1	103	57	3	167

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001330677.2	RefSeq	NP_001317606.1	8	MANE Select
ENST00000369429.5	Ensembl	ENSP00000358437.3	8	MANE Select
NM_152380.3	RefSeq	NP_689593.2	7	Standard
ENST00000207157.7	Ensembl	ENSP00000207157.3	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
embryonic cranial skeleton morphogenesis

Molecular Function

RNA polymerase II proximal promoter 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

Tle3-Aes complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000207157
Coding exons: 7
Length: 106511
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125735
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.993	218	263	0.828	0.0000133	3264
Missense (PolyPhen)		80	118.58	0.67463		1540
Synonymous	1.04	85	98.1	0.867	0.00000536	979
Loss of Function	3.43	4	20.9	0.191	0.00000122	230

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable transcriptional regulator involved in the development of the skeleton of the limb, vertebral column and head. Acts by controlling the number of mesenchymal precursor cells and chondrocytes (By similarity). {ECO:0000250}.;
Disease: DISEASE: Cousin syndrome (COUSS) [MIM:260660]: Defined as pelviscapular dysplasia with epiphyseal abnormalities, congenital dwarfism and facial dysmorphy (frontal bossing, hypertelorism, narrow palpebral fissures, deep set globes, strabismus, low-set posteriory rotated and unusually formed external ears, dysplasia of conchae, small chin, short neck with redundant skin folds, and a low hairline). Intelligence may vary from normal to moderately impaired. Radiographic features comprise aplasia of the body of the scapula, hypoplasia of the iliac bone, humeroradial synosthosis, dislocation of the femoral heads, and moderate brachydactyly. {ECO:0000269|PubMed:19068278}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.143
RVIS EVS: 0.17
RVIS percentile EVS: 65.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.635

Gene Damage Prediction

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