HOXD3

homeobox D3, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 2:176136611-176173102

Previous symbols: [ "HOX4A", "HOX4", "HOX1D" ]

Links

ENSG00000128652 ∙ NCBI:3232 ∙ OMIM:142980 ∙ HGNC:5137 ∙ Uniprot:P31249 ∙ 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 HOXD3 gene.

• Inborn genetic diseases (22 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXD3 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			22			22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	22	0	1

Variants in HOXD3

This is a list of pathogenic ClinVar variants found in the HOXD3 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)
2-176169182-A-G		not specified	Uncertain significance (Jul 21, 2022)
2-176169265-C-A		not specified	Uncertain significance (Jun 09, 2022)
2-176169267-A-C			Benign (Apr 03, 2018)
2-176169387-G-A		not specified	Uncertain significance (Nov 28, 2023)
2-176169389-G-A		not specified	Uncertain significance (Mar 29, 2023)
2-176169415-G-C		not specified	Uncertain significance (Aug 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOXD3	protein_coding	protein_coding	ENST00000468418	2	36491

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.441	0.558	125743	0	4	125747	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	207	256	0.809	0.0000125	2763
Missense in Polyphen		76	78.572	0.96726		747
Synonymous	0.644	104	113	0.923	0.00000576	908
Loss of Function	2.75	3	14.1	0.212	6.69e-7	154

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000102	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000881	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
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: 0.205

Intolerance Scores

• loftool: 0.0697
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.73

Haploinsufficiency Scores

• pHI: 0.307
• hipred: Y
• hipred_score: 0.735
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.976

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hoxd3
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; embryo phenotype; respiratory 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); 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); hematopoietic system phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: transcription, DNA-templated;cell-matrix adhesion;Notch signaling pathway;anterior/posterior pattern specification;positive regulation of gene expression;glossopharyngeal nerve morphogenesis;thyroid gland development;positive regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;embryonic skeletal system morphogenesis;cartilage development
• Cellular component: nucleus;nucleoplasm;aggresome;nuclear body
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;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 transcription factor activity;protein binding