HOXD4

homeobox D4, the group of HOXL subclass homeoboxes|MicroRNA protein coding host genes

Basic information

Region (hg38): 2:176151549-176153226

Previous symbols: [ "HOX4B", "HOX4" ]

Links

ENSG00000170166 ∙ NCBI:3233 ∙ OMIM:142981 ∙ HGNC:5138 ∙ Uniprot:P09016 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOXD4 gene.

• Inborn genetic diseases (12 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXD4 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					1	1
missense			12	1		13
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	12	1	1

Variants in HOXD4

This is a list of pathogenic ClinVar variants found in the HOXD4 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-176151697-G-A			Likely benign (Aug 16, 2018)
2-176151724-G-C		not specified	Uncertain significance (Dec 15, 2023)
2-176151731-G-A		not specified	Uncertain significance (Jul 08, 2022)
2-176151746-G-A		not specified	Uncertain significance (Jun 10, 2022)
2-176151768-C-T			Benign (Feb 16, 2018)
2-176151776-C-A		not specified	Uncertain significance (Feb 10, 2022)
2-176151793-C-T		not specified	Uncertain significance (Aug 17, 2021)
2-176151808-G-A		not specified	Uncertain significance (May 30, 2022)
2-176151875-A-T		Leukemia, acute lymphoblastic, susceptibility to	Uncertain significance (Apr 01, 2005)
2-176151907-C-A		not specified	Uncertain significance (Sep 01, 2021)
2-176151944-C-A		not specified	Uncertain significance (Jul 12, 2023)
2-176151982-G-C		not specified	Uncertain significance (Sep 22, 2023)
2-176152033-T-C		not specified	Uncertain significance (Feb 28, 2024)
2-176152072-G-T			Benign (Jun 29, 2018)
2-176152722-G-A		not specified	Uncertain significance (Jul 19, 2023)
2-176152725-G-A		not specified	Uncertain significance (May 31, 2023)
2-176152761-G-T		not specified	Uncertain significance (Nov 21, 2022)
2-176152867-C-G		not specified	Uncertain significance (Dec 06, 2022)
2-176152883-C-A		not specified	Uncertain significance (Aug 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOXD4	protein_coding	protein_coding	ENST00000306324	2	2005

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00545	0.904	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.423	169	154	1.10	0.00000769	1610
Missense in Polyphen		66	58.251	1.133		631
Synonymous	-1.18	86	73.2	1.18	0.00000391	539
Loss of Function	1.45	5	9.93	0.504	4.30e-7	109

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000708	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
• Pathway: Activation of anterior HOX genes in hindbrain development during early embryogenesis (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.266
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.569
• hipred: N
• hipred_score: 0.361
• ghis: 0.423

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.841

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hoxd4
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; skeleton phenotype; reproductive system 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)

Zebrafish Information Network

• Gene name: hoxd4a
• Affected structure: vasculature
• Phenotype tag: abnormal
• Phenotype quality: lacks parts or has fewer parts of type

Gene ontology

• Biological process: skeletal system development;multicellular organism development;anterior/posterior pattern specification;positive regulation of transcription by RNA polymerase II;embryonic skeletal system morphogenesis
• Cellular component: nucleus;nucleoplasm;cell junction
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;activating transcription factor binding