DLX3

distal-less homeobox 3, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 17:49990005-49995224

Links

ENSG00000064195 ∙ NCBI:1747 ∙ OMIM:600525 ∙ HGNC:2916 ∙ Uniprot:O60479 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• tricho-dento-osseous syndrome (Moderate), mode of inheritance: AD
• hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (Limited), mode of inheritance: AD
• tricho-dento-osseous syndrome (Supportive), mode of inheritance: AD
• hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (Supportive), mode of inheritance: AD
• tricho-dento-osseous syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Trichodontoosseous syndrome; Amelogenesis imperfecta, type IV	AD	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; Dental; Dermatologic; Musculoskeletal	9467018; 9783705; 10466415; 15666299; 18203197; 18362318; 18492670; 19608154; 21252474

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DLX3 gene.

• Tricho-dento-osseous syndrome (2 variants)
• not provided (2 variants)
• Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (1 variants)
• DLX3-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLX3 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		3	42	3	2	50
nonsense			1			1
start loss						0
frameshift	2	2				4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			30	13	26	69
Total	2	5	73	43	32

Variants in DLX3

This is a list of pathogenic ClinVar variants found in the DLX3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-49990012-C-T		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 12, 2018)
17-49990107-C-T		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 12, 2018)
17-49990109-C-T		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 13, 2018)
17-49990182-G-A		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 13, 2018)
17-49990189-A-C		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Likely benign (Jan 13, 2018)
17-49990191-A-T		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 13, 2018)
17-49990217-G-C		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 12, 2018)
17-49990221-C-T		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 13, 2018)
17-49990245-A-G		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 12, 2018)
17-49990265-G-C		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 13, 2018)
17-49990292-TA-T		Amelogenesis Imperfecta, Dominant	Likely benign (Jun 14, 2016)
17-49990292-T-TA		Amelogenesis Imperfecta, Dominant	Uncertain significance (Jun 14, 2016)
17-49990312-T-G		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 13, 2018)
17-49990348-CT-C		Amelogenesis Imperfecta, Dominant	Likely benign (Jun 14, 2016)
17-49990348-CTT-C		Amelogenesis Imperfecta, Dominant	Uncertain significance (Jun 14, 2016)
17-49990353-T-C		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 13, 2018)
17-49990492-C-A		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 12, 2018)
17-49990501-C-G		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 13, 2018)
17-49990529-C-T		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 12, 2018)
17-49990530-G-A		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 13, 2018)
17-49990531-G-A		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 13, 2018)
17-49990589-T-C		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 12, 2018)
17-49990649-G-A		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Benign (Jan 13, 2018)
17-49990696-G-T		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 12, 2018)
17-49990705-C-T		Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DLX3	protein_coding	protein_coding	ENST00000434704	3	5220

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00255	0.938	125706	0	15	125721	0.0000597

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.957	134	169	0.793	0.00000904	1822
Missense in Polyphen		41	57.023	0.719		567
Synonymous	0.659	73	80.5	0.907	0.00000452	598
Loss of Function	1.65	6	12.2	0.491	5.29e-7	130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000881	0.0000879
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Likely to play a regulatory role in the development of the ventral forebrain. May play a role in craniofacial patterning and morphogenesis.
• Disease: DISEASE: Trichodentoosseous syndrome (TDO) [MIM:190320]: An autosomal dominant disease characterized by curly kinky hair at birth, enamel hypoplasia, taurodontism, thickening of cortical bones and variable expression of craniofacial morphology. {ECO:0000269|PubMed:9467018}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Amelogenesis imperfecta 4 (AI4) [MIM:104510]: An autosomal dominant defect of enamel formation associated with enlarged pulp chambers. Enamel is thin, teeth are small and widely spaced. {ECO:0000269|PubMed:15666299}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.212

Intolerance Scores

• loftool: 0.195
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

• pHI: 0.524
• hipred: Y
• hipred_score: 0.588
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.294

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dlx3
• Phenotype: growth/size/body region 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); endocrine/exocrine gland phenotype; embryo phenotype; 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); 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)

Zebrafish Information Network

• Gene name: dlx3b
• Affected structure: otolith
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: blood vessel development;placenta development;regulation of transcription by RNA polymerase II;cell differentiation;epithelial cell differentiation;odontogenesis of dentin-containing tooth;positive regulation of transcription by RNA polymerase II;odontoblast differentiation
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding;sequence-specific DNA binding