HOXB1

protein-coding

homeobox B1, the group of HOXL subclass homeoboxes

Gene summary

This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXB genes located in a cluster on chromosome 17. [provided by RefSeq, Jul 2008]

Previous symbols:

HOX2
HOX2I

MANE transcript

NM_002144.4

Inheritance

ClinVar variants

P:3U:49B:14

Top phenotype

Facial paresis, hereditary congenital, 3

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr17:48,528,526-48,531,011

External References & Databases

Ensembl (ENSG00000120094)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

facial paresis, hereditary congenital, 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013880

Submitter: G2P

facial paresis, hereditary congenital, 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013880

Submitter: Labcorp Genetics (formerly Invitae)

congenital hereditary facial paralysis-variable hearing loss syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017627

Submitter: Orphanet

facial paresis, hereditary congenital, 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013880

Submitter: Ambry Genetics

facial paresis, hereditary congenital, 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013880

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Facial paresis, hereditary congenital, 3AR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 22770981

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HOXB1 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 43

not providedTotal: 14

HOXB1-related disorderTotal: 5

Facial paresis, hereditary congenital, 3Total: 5

not specifiedTotal: 4

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002144.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	8 clinvar	2 clinvar	11
missense	2 clinvar		47 clinvar	4 clinvar		53
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	3	0	49	12	2	66

Highest pathogenic variant AF is 0.00000438177

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002144.4	RefSeq	NP_002135.2	2	MANE Select
ENST00000239174.7	Ensembl	ENSP00000355140.5	2	MANE Select
ENST00000577092.1	Ensembl	ENSP00000459066.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
hoxb1a	Danio rerio	Structure: Mauthner neuron Quality: absent abnormal

Gene / Model

Organism

Observed Phenotype

hoxb1a

Danio rerio

Structure: Mauthner neuron

Quality: absent

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
Neural Crest Differentiation
Activation of anterior HOX genes in hindbrain development during early embryogenesis

Biological Process

regulation of transcription, DNA-templated
multicellular organism development
pattern specification process
anterior/posterior pattern specification
rhombomere 4 development

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000239174
Coding exons: 2
Length: 2472
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125734
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.860	158	191	0.825	0.0000115	1899
Missense (PolyPhen)		41	66.22	0.61915		714
Synonymous	0.820	74	83.5	0.886	0.00000552	625
Loss of Function	2.27	4	12.7	0.314	8.11e-7	121

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000098	0.000098	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

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. Acts on the anterior body structures.;
Disease: DISEASE: Facial paresis, hereditary congenital, 3 (HCFP3) [MIM:614744]: A form of facial paresis, a disease characterized by isolated dysfunction of the facial nerve (CN VII). HCFP3 patients are affected by bilateral facial palsy, facial muscle weakness of muscles innervated by CN VII, hearing loss, and strabismus. {ECO:0000269|PubMed:22770981}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.166

Intolerance Scores

LoFtool: 0.120
RVIS EVS: 0.19
RVIS percentile EVS: 67.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.489

Gene Damage Prediction

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