PHOX2A

paired like homeobox 2A, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 11:72239077-72245664

Previous symbols: [ "ARIX", "FEOM2" ]

Links

ENSG00000165462 ∙ NCBI:401 ∙ OMIM:602753 ∙ HGNC:691 ∙ Uniprot:O14813 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• fibrosis of extraocular muscles, congenital, 2 (Strong), mode of inheritance: AR
• congenital fibrosis of extraocular muscles (Supportive), mode of inheritance: AD
• fibrosis of extraocular muscles, congenital, 2 (Strong), mode of inheritance: AR
• fibrosis of extraocular muscles, congenital, 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fibrosis of extraocular muscles, congenital, 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	11600883

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHOX2A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHOX2A 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				3	1	4
missense			14			14
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	1	2
Total	0	0	14	5	2

Variants in PHOX2A

This is a list of pathogenic ClinVar variants found in the PHOX2A region.

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

Position	Type	Phenotype	Significance	ClinVar
11-72239759-T-C		Inborn genetic diseases	Uncertain significance (May 16, 2022)
11-72239771-G-T		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
11-72239782-C-T			Likely benign (Jan 01, 2019)
11-72239907-C-T		PHOX2A-related disorder	Uncertain significance (May 19, 2023)
11-72239915-G-A		PHOX2A-related disorder	Uncertain significance (Jun 22, 2023)
11-72239930-T-A		PHOX2A-related disorder	Uncertain significance (May 17, 2024)
11-72240009-C-T		Inborn genetic diseases	Uncertain significance (Sep 15, 2021)
11-72240067-C-T			Likely benign (Jul 16, 2018)
11-72240079-G-T		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
11-72240095-C-T		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
11-72240099-G-A		Inborn genetic diseases	Uncertain significance (Feb 06, 2024)
11-72240115-GGCGCCCGCC-G		PHOX2A-related disorder	Benign (Dec 31, 2019)
11-72240131-G-T		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
11-72240149-G-C		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
11-72240158-T-C		Inborn genetic diseases	Uncertain significance (Oct 13, 2023)
11-72240199-C-T		Fibrosis of extraocular muscles, congenital, 2	Pathogenic (Nov 01, 2001)
11-72241151-G-A		Inborn genetic diseases	Uncertain significance (Apr 01, 2024)
11-72241251-C-G		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
11-72243769-G-T		not specified	Likely benign (-)
11-72243787-C-T		Fibrosis of extraocular muscles, congenital, 2	Pathogenic (Nov 01, 2001)
11-72243790-G-A		Fibrosis of extraocular muscles, congenital, 2	Uncertain significance (Apr 04, 2024)
11-72243803-C-G		Inborn genetic diseases	Uncertain significance (Nov 30, 2022)
11-72243803-C-T		PHOX2A-related disorder	Uncertain significance (Mar 23, 2024)
11-72243849-G-A		not specified	Benign (-)
11-72243855-G-A			Likely benign (Jul 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHOX2A	protein_coding	protein_coding	ENST00000298231	3	6588

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.490	0.491	125589	0	2	125591	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	63	110	0.571	0.00000585	1761
Missense in Polyphen		11	21.643	0.50825		217
Synonymous	2.29	29	49.5	0.586	0.00000267	625
Loss of Function	1.88	1	5.96	0.168	2.55e-7	94

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in regulating the specificity of expression of the catecholamine biosynthetic genes. Acts as a transcription activator/factor. Could maintain the noradrenergic phenotype.
• Disease: DISEASE: Fibrosis of extraocular muscles, congenital, 2 (CFEOM2) [MIM:602078]: A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 2 may result from the defective development of the oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei. {ECO:0000269|PubMed:11600883}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways (Consensus)

Recessive Scores

• pRec: 0.156

Haploinsufficiency Scores

• pHI: 0.339
• hipred: Y
• hipred_score: 0.634
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phox2a
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism 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); 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: phox2a
• Affected structure: pharyngeal arch
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: noradrenergic neuron differentiation;nervous system development;somatic motor neuron differentiation;oculomotor nerve formation;trochlear nerve formation;locus ceruleus development;midbrain development;regulation of respiratory gaseous exchange;positive regulation of transcription by RNA polymerase II;autonomic nervous system development;enteric nervous system development;sympathetic nervous system development;dopaminergic neuron differentiation
• Cellular component: nuclear chromatin;nucleus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity