DLX4

distal-less homeobox 4, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 17:49968587-49974959

Previous symbols: [ "DLX7", "DLX9" ]

Links

ENSG00000108813 ∙ NCBI:1748 ∙ OMIM:601911 ∙ HGNC:2917 ∙ Uniprot:Q92988 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• orofacial cleft 15 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Orofacial cleft 15	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	25954033

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DLX4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLX4 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				8	1	9
missense			22	3		25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	22	11	1

Variants in DLX4

This is a list of pathogenic ClinVar variants found in the DLX4 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-49969536-C-G		not specified	Uncertain significance (Jun 02, 2023)
17-49969542-C-G		DLX4-related disorder	Likely benign (Aug 04, 2021)
17-49969563-C-T		not specified	Uncertain significance (Jan 30, 2024)
17-49969578-C-T		not specified	Uncertain significance (Jun 02, 2024)
17-49969596-C-G		not specified	Uncertain significance (Jan 10, 2023)
17-49969607-T-C		not specified	Uncertain significance (Sep 25, 2023)
17-49969610-T-A		not specified	Uncertain significance (Oct 25, 2023)
17-49969672-C-T		Orofacial cleft 15	Benign/Likely benign (Apr 06, 2022)
17-49969697-G-A		not specified	Uncertain significance (Jun 01, 2024)
17-49969699-G-A		DLX4-related disorder	Likely benign (Sep 17, 2019)
17-49969709-C-A		not specified	Uncertain significance (Nov 06, 2023)
17-49969745-G-C		not specified	Uncertain significance (Sep 30, 2021)
17-49969750-A-G			Likely benign (Dec 31, 2019)
17-49973042-G-A		DLX4-related disorder	Likely benign (Mar 25, 2023)
17-49973076-C-G		not specified	Uncertain significance (May 31, 2023)
17-49973096-C-G		not specified	Uncertain significance (Jul 26, 2022)
17-49973111-C-G		not specified	Uncertain significance (Mar 08, 2024)
17-49973158-C-A			Likely benign (Dec 27, 2017)
17-49973191-GC-TA			Uncertain significance (Sep 16, 2018)
17-49973193-G-C		DLX4-related disorder	Likely benign (Dec 31, 2019)
17-49973217-C-T		not specified	Uncertain significance (Dec 15, 2023)
17-49973224-C-T		DLX4-related disorder	Likely benign (Apr 07, 2021)
17-49973251-C-A		DLX4-related disorder	Likely benign (Dec 04, 2023)
17-49973253-G-C		not specified	Uncertain significance (Aug 19, 2023)
17-49973255-C-T		not specified	Uncertain significance (Aug 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DLX4	protein_coding	protein_coding	ENST00000240306	3	5988

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0169	0.897	125726	0	9	125735	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0197	128	127	1.00	0.00000573	1503
Missense in Polyphen		30	27.604	1.0868		370
Synonymous	0.395	58	62.0	0.936	0.00000284	524
Loss of Function	1.45	4	8.57	0.467	3.66e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000124
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000191	0.0000176
Middle Eastern	0.0000546	0.0000544
South Asian	0.0000916	0.0000653
Other	0.000216	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in determining the production of hemoglobin S. May act as a repressor. During embryonic development, plays a role in palatogenesis. {ECO:0000269|PubMed:11909945, ECO:0000269|PubMed:25954033}.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.291
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• pHI: 0.778
• hipred: N
• hipred_score: 0.428
• ghis: 0.429

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dlx4

Zebrafish Information Network

• Gene name: dlx4b
• Affected structure: neurocranium
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;regulation of transcription by RNA polymerase II;multicellular organism development
• 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 repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;sequence-specific DNA binding