HOXA4

protein-coding

homeobox A4, the group of HOXL subclass homeoboxes

Gene summary

In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. [provided by RefSeq, Jul 2008]

Previous symbols:

HOX1D
HOX1

MANE transcript

NM_002141.5

Inheritance

ClinVar variants

U:81B:9

Top phenotype

HOXA4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr7:27,128,507-27,130,780

External References & Databases

Ensembl (ENSG00000197576)

Transcript & Mutation Effects

hg38 • Region Span ~2.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

microtia with meatal atresia and conductive deafnessLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0009634

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HOXA4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 79

HOXA4-related disorderTotal: 8

not providedTotal: 3

EBV-positive nodal T- and NK-cell lymphomaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002141.5. 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	7 clinvar		8
missense			80 clinvar	2 clinvar		82
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	81	9	0	90

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002141.5	RefSeq	NP_002132.3	2	MANE Select
ENST00000360046.10	Ensembl	ENSP00000353151.5	2	MANE Select
ENST00000511914.1	Ensembl	ENSP00000448015.1	2	Standard
ENST00000610970.1	Ensembl	ENSP00000479166.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Activation of anterior HOX genes in hindbrain development during early embryogenesis

Biological Process

skeletal system development
anatomical structure morphogenesis
anterior/posterior pattern specification
positive regulation of transcription by RNA polymerase II
embryonic skeletal system morphogenesis

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

Cellular Component

nucleus
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360046
Coding exons: 2
Length: 2293
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125748
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.332	142	131	1.08	0.00000737	1952
Missense (PolyPhen)		48	39.879	1.2037		440
Synonymous	-0.272	61	58.4	1.05	0.00000322	663
Loss of Function	0.193	8	8.61	0.929	5.05e-7	101

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

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. Binds to sites in the 5'-flanking sequence of its coding region with various affinities. The consensus sequences of the high and low affinity binding sites are 5'-TAATGA[CG]-3' and 5'-CTAATTTT- 3'.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.572

Gene Damage Prediction

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