RAX

protein-coding

retina and anterior neural fold homeobox, the group of PRD class homeoboxes and pseudogenes

Gene summary

This gene encodes a homeobox-containing transcription factor that functions in eye development. The gene is expressed early in the eye primordia, and is required for retinal cell fate determination and also regulates stem cell proliferation. Mutations in this gene have been reported in patients with defects in ocular development, including microphthalmia, anophthalmia, and coloboma.[provided by RefSeq, Oct 2009]

MANE transcript

NM_013435.3

Inheritance

ClinVar variants

P:10U:98B:28

Top phenotype

Microphthalmia, syndromic 16

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr18:59,267,035-59,274,086

External References & Databases

Ensembl (ENSG00000134438)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated microphthalmia 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012604

Submitter: PanelApp Australia

isolated microphthalmia 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012604

Submitter: Labcorp Genetics (formerly Invitae)

isolated microphthalmia 3DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012604

Submitter: G2P

colobomaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001476

Submitter: G2P

Clinical Genomic Database (CGD)

Microphthalmia, syndromic 16AR

Manifestation: Craniofacial; Endocrine; Ophthalmologic

Intervention: Endocrine

Rationale: The condition has been described as including panhypopituitarism in some individuals, and awareness may allow early diagnosis and medical management of endocrine manifestations

Refs: 14662654; 18783408; 22736936; 24033328; 28831107; 30811539

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAX variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 78

Isolated microphthalmia 3Total: 62

not providedTotal: 32

RAX-related disorderTotal: 4

not specifiedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013435.3. 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			5 clinvar	25 clinvar		30
missense	2 clinvar		93 clinvar	2 clinvar	1 clinvar	98
nonsense	3 clinvar	1 clinvar				4
start loss						0
frameshift	2 clinvar	2 clinvar				4
splice donor/acceptor (+/-2bp)						0
Total	7	3	98	27	1	136

Highest pathogenic variant AF is 0.000013010298

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_013435.3	RefSeq	NP_038463.2	3	MANE Select
ENST00000334889.4	Ensembl	ENSP00000334813.3	3	MANE Select
ENST00000256852.7	Ensembl	ENSP00000256852.7	2	Standard
ENST00000256852.8	Ensembl	ENSP00000256852.7	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rx3	Danio rerio	Structure: ethmoid cartilage Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

rx3

Danio rerio

Structure: ethmoid cartilage

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

pattern specification process
visual perception
hypothalamus development
camera-type eye development
positive regulation of transcription by RNA polymerase II

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334889
Coding exons: 3
Length: 7052
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125733
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.189	168	175	0.960	0.00000825	2124
Missense (PolyPhen)		50	63.257	0.79042		727
Synonymous	-0.147	90	88.2	1.02	0.00000423	783
Loss of Function	1.86	3	9.02	0.333	3.93e-7	103

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	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000019	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation. Binds to the photoreceptor conserved element-I (PCE-1/Ret 1) in the photoreceptor cell-specific arrestin promoter.;

Recessive Scores

pRec: 0.110

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.673

Gene Damage Prediction

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