IRX3

protein-coding

iroquois homeobox 3, the group of TALE class homeoboxes and pseudogenes

Gene summary

IRX3 is a member of the Iroquois homeobox gene family (see IRX1; MIM 606197) and plays a role in an early step of neural development (Bellefroid et al., 1998 [PubMed 9427753]). Members of this family appear to play multiple roles during pattern formation of vertebrate embryos (Lewis et al., 1999 [PubMed 10370142]).[supplied by OMIM, Aug 2009]

MANE transcript

NM_024336.3

Inheritance

—

ClinVar variants

U:84B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr16:54,283,304-54,286,787

External References & Databases

Ensembl (ENSG00000177508)

Transcript & Mutation Effects

hg38 • Region Span ~3.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IRX3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024336.3. 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	2 clinvar	2 clinvar	5
missense			83 clinvar			83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	84	2	2	88

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024336.3	RefSeq	NP_077312.2	4	MANE Select
ENST00000329734.4	Ensembl	ENSP00000331608.3	4	MANE Select
ENST00000558054.1	Ensembl	ENSP00000463991.1	3	Standard
ENST00001033369.1	Ensembl	ENSP00000703186.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
irx3a	Danio rerio	Structure: pancreatic bud Quality: has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

irx3a

Danio rerio

Structure: pancreatic bud

Quality: has fewer parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

FTO Obesity Variant Mechanism

Biological Process

metanephros development
regulation of transcription by RNA polymerase II
mesoderm development
negative regulation of neuron differentiation
positive regulation of neuron differentiation

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
sequence-specific DNA binding

Cellular Component

nucleus
cytoplasm
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000329734
Coding exons: 4
Length: 3460
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125703
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.581	191	215	0.889	0.00000987	3033
Missense (PolyPhen)		50	60.242	0.82999		738
Synonymous	-1.06	115	101	1.13	0.00000504	1089
Loss of Function	2.88	1	11.6	0.0862	4.95e-7	170

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0.000067	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor. Involved in SHH-dependent neural patterning. Together with NKX2-2 and NKX6-1 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class I proteins of neuronal progenitor factors, which are repressed by SHH signals. Involved in the transcriptional repression of MNX1 in non-motor neuron cells (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.144

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.467

Gene Damage Prediction

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