HOXA1

homeobox A1, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 7:27092992-27096000

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
• syndromic intellectual disability (Definitive), mode of inheritance: AR
• human HOXA1 syndromes (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Athabaskan brainstem dysgenesis syndrome; Bosley-Salih-Alorainy syndrome	AR	Audiologic/Otolaryngologic; Cardiovascular	Early 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 management	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Neurologic	16155570; 18412118; 20075099

ClinVar

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

• Human HOXA1 syndromes (2 variants)
• not provided (2 variants)
• Bosley-Salih-Alorainy 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.

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			7	10		17
missense			35	1	1	37
nonsense	1	1				2
start loss						0
frameshift	1					1
inframe indel			1	7	2	10
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			20	4	3	27
Total	2	1	63	22	6

Highest pathogenic variant AF is 0.00000657

Variants in HOXA1

This is a list of pathogenic ClinVar variants found in the HOXA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-27093003-T-C		Human HOXA1 syndromes	Likely benign (Jan 13, 2018)
7-27093053-G-C		Bosley-Salih-Alorainy syndrome	Uncertain significance (Jun 14, 2016)
7-27093095-A-G		Bosley-Salih-Alorainy syndrome	Uncertain significance (Jun 14, 2016)
7-27093290-G-A		Bosley-Salih-Alorainy syndrome	Uncertain significance (Jun 14, 2016)
7-27093350-G-A		Human HOXA1 syndromes	Benign (Jan 12, 2018)
7-27093382-A-T		Human HOXA1 syndromes	Uncertain significance (Jan 13, 2018)
7-27093460-G-C		Human HOXA1 syndromes	Uncertain significance (Jan 12, 2018)
7-27093487-C-T		Bosley-Salih-Alorainy syndrome	Uncertain significance (Jun 14, 2016)
7-27093533-T-C		Bosley-Salih-Alorainy syndrome	Likely benign (Jun 14, 2016)
7-27093620-T-C		Human HOXA1 syndromes	Uncertain significance (Jan 12, 2018)
7-27093877-C-G		Bosley-Salih-Alorainy syndrome	Uncertain significance (Jun 14, 2016)
7-27093970-A-T		Bosley-Salih-Alorainy syndrome	Likely benign (Jun 14, 2016)
7-27094095-G-A		Human HOXA1 syndromes	Uncertain significance (Jan 13, 2018)
7-27094103-C-T		Human HOXA1 syndromes	Uncertain significance (Jan 13, 2018)
7-27094109-G-T		Bosley-Salih-Alorainy syndrome	Uncertain significance (Jun 14, 2016)
7-27094159-G-C		Human HOXA1 syndromes	Uncertain significance (Jan 12, 2018)
7-27094190-C-G		Bosley-Salih-Alorainy syndrome	Uncertain significance (Jun 14, 2016)
7-27094208-C-T		Human HOXA1 syndromes	Uncertain significance (Jan 13, 2018)
7-27094257-C-G		Human HOXA1 syndromes	Uncertain significance (Jan 13, 2018)
7-27094257-C-T		Bosley-Salih-Alorainy syndrome • Human HOXA1 syndromes	Uncertain significance (Jun 14, 2016)
7-27094259-C-T		Bosley-Salih-Alorainy syndrome	Uncertain significance (Jun 14, 2016)
7-27094384-G-T		Bosley-Salih-Alorainy syndrome	Benign/Likely benign (Jun 19, 2021)
7-27094447-G-A		Inborn genetic diseases	Uncertain significance (Jan 18, 2018)
7-27094467-G-A		Inborn genetic diseases	Likely benign (Sep 26, 2017)
7-27094474-G-A		Inborn genetic diseases	Uncertain significance (Mar 27, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOXA1	protein_coding	protein_coding	ENST00000343060	2	3004

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.285	0.711	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.103	196	192	1.02	0.0000105	2178
Missense in Polyphen		102	98.188	1.0388		1152
Synonymous	-0.732	93	84.4	1.10	0.00000516	686
Loss of Function	2.46	3	12.3	0.243	5.97e-7	134

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000530	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000327	0.000326

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

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

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