GeneBe

HOXA1

homeobox A1, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 7:27092993-27096000

Previous symbols: [ "HOX1F", "HOX1" ]

Links

ENSG00000105991 ∙ NCBI:3198 ∙ OMIM:142955 ∙ HGNC:5099 ∙ Uniprot:P49639 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • human HOXA1 syndromes (Definitive), mode of inheritance: AR
  • human HOXA1 syndromes (Moderate), mode of inheritance: AR
  • Bosley-Salih-Alorainy syndrome (Supportive), mode of inheritance: AR
  • human HOXA1 syndromes (Supportive), mode of inheritance: AR
  • human HOXA1 syndromes (Strong), mode of inheritance: AR
  • syndromic intellectual disability (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Athabaskan brainstem dysgenesis syndrome; Bosley-Salih-Alorainy syndromeARAudiologic/Otolaryngologic; CardiovascularEarly recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The conditions can involve congenital cardiac anomalies, and awareness may allow early managementAudiologic/Otolaryngologic; Cardiovascular; Craniofacial; Neurologic16155570; 18412118; 20075099

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOXA1 gene.

  • Inborn_genetic_diseases (73 variants)
  • Bosley-Salih-Alorainy_syndrome (20 variants)
  • not_provided (19 variants)
  • Human_HOXA1_syndromes (13 variants)
  • HOXA1-related_disorder (7 variants)
  • not_specified (3 variants)
  • Intellectual_disability (3 variants)
  • Bilateral_microtia-deafness-cleft_palate_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005522.5. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
13
clinvar
1
clinvar
 22
missense
61
clinvar
4
clinvar
 65
nonsense
2
clinvar
1
clinvar
 3
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
0
Total 4 1 69 17 1

Highest pathogenic variant AF is 0.00000657255

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
HOXA1protein_codingprotein_codingENST00000343060 23004
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.2850.7111257360121257480.0000477
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.1031961921.020.00001052178
Missense in Polyphen10298.1881.03881152
Synonymous-0.7329384.41.100.00000516686
Loss of Function2.46312.30.2435.97e-7134

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00005780.0000578
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00004620.0000462
European (Non-Finnish)0.00005300.0000527
Middle Eastern0.000.00
South Asian0.00003270.0000327
Other0.0003270.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: Sequence-specific transcription factor (By similarity). Regulates multiple developmental processes including brainstem, inner and outer ear, abducens nerve and cardiovascular development and morphogenesis as well as cognition and behavior (PubMed:16155570). Also part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Acts on the anterior body structures. Seems to act in the maintenance and/or generation of hindbrain segments (By similarity). Activates transcription in the presence of PBX1A and PKNOX1 (By similarity). {ECO:0000250|UniProtKB:P09022, ECO:0000250|UniProtKB:Q90423, ECO:0000269|PubMed:16155570}.;
Disease
DISEASE: Athabaskan brainstem dysgenesis syndrome (ABDS) [MIM:601536]: Characterized by horizontal gaze palsy, sensorineural deafness, central hypoventilation, and developmental delay. Some patients had swallowing dysfunction, vocal cord paralysis, facial paresis, seizures, and cardiac outflow tract anomalies. {ECO:0000269|PubMed:16155570}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bosley-Salih-Alorainy syndrome (BSAS) [MIM:601536]: A disease characterized by horizontal gaze abnormalities, deafness, facial weakness, vascular malformations of the internal carotid arteries and cardiac outflow trac. Some patients manifest mental retardation and autism spectrum disorder. Affected individuals do not suffer from central hypoventilation. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Neural Crest Differentiation;Endoderm Differentiation;Activation of anterior HOX genes in hindbrain development during early embryogenesis (Consensus)

Recessive Scores

pRec
0.229

Intolerance Scores

loftool
0.215
rvis_EVS
0.06
rvis_percentile_EVS
58.74

Haploinsufficiency Scores

pHI
0.803
hipred
N
hipred_score
0.429
ghis
0.401

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.962

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Hoxa1
Phenotype
digestive/alimentary phenotype; hearing/vestibular/ear 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); vision/eye phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system 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); hematopoietic 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); normal phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype;

Gene ontology

Biological process
multicellular organism development;sensory perception of sound;optokinetic behavior;anatomical structure morphogenesis;abducens nerve formation;outer ear morphogenesis;positive regulation of transcription by RNA polymerase II;embryonic neurocranium morphogenesis;inner ear development;artery morphogenesis;regulation of behavior;cognition;neuromuscular process;artery development;semicircular canal formation;cochlea development;cochlea morphogenesis
Cellular component
nucleus
Molecular function
DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;identical protein binding;sequence-specific DNA binding