PRRX1

paired related homeobox 1, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 1:170662728-170739421

Previous symbols: [ "PMX1" ]

Links

ENSG00000116132 ∙ NCBI:5396 ∙ OMIM:167420 ∙ HGNC:9142 ∙ Uniprot:P54821 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• agnathia-otocephaly complex (Supportive), mode of inheritance: AD
• agnathia-otocephaly complex (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Agnathia-otocephaly complex	AD/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	Audiologic/Otolaryngologic; Craniofacial	12244557; 21294718; 22211708; 23444262

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRRX1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRRX1 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				5		5
missense			9	1	2	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				1		1
Total	0	0	9	7	2

Variants in PRRX1

This is a list of pathogenic ClinVar variants found in the PRRX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-170664233-C-T		PRRX1-related disorder	Likely benign (Nov 22, 2023)
1-170664249-C-T		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
1-170664267-G-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2023)
1-170664307-C-A		Inborn genetic diseases	Uncertain significance (Nov 07, 2024)
1-170664360-A-C		not specified	Uncertain significance (May 28, 2024)
1-170664360-A-T		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
1-170664362-G-A		Inborn genetic diseases	Uncertain significance (Apr 26, 2024)
1-170664369-G-T		PRRX1-related disorder	Uncertain significance (Mar 05, 2024)
1-170664403-G-A			Benign (Dec 31, 2019)
1-170664419-G-T			Likely benign (Dec 04, 2017)
1-170664428-C-T			Likely benign (Dec 31, 2019)
1-170719746-GA-G		Agnathia-otocephaly complex	Pathogenic (Sep 01, 2012)
1-170719746-G-GAAAA		Agnathia-otocephaly complex	Pathogenic (Apr 01, 2013)
1-170719794-A-G			Benign (Dec 31, 2019)
1-170719801-T-C		Agnathia-otocephaly complex	Likely pathogenic (Sep 01, 2020)
1-170719822-T-C		Agnathia-otocephaly complex	Pathogenic (Mar 01, 2011)
1-170719827-C-T		Agnathia-otocephaly complex	Uncertain significance (Aug 07, 2018)
1-170719908-C-G		PRRX1-related disorder	Benign (Dec 31, 2019)
1-170726219-G-A		Craniosynostosis syndrome	Uncertain significance (Oct 09, 2024)
1-170726270-G-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
1-170726274-G-A		Inborn genetic diseases	Uncertain significance (Jul 27, 2022)
1-170726294-C-G		PRRX1-related disorder	Likely benign (Feb 28, 2019)
1-170726302-C-G		Inborn genetic diseases	Uncertain significance (Dec 10, 2024)
1-170726331-C-G		PRRX1-related disorder	Uncertain significance (Feb 14, 2023)
1-170726337-A-G		Inborn genetic diseases	Uncertain significance (Aug 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRRX1	protein_coding	protein_coding	ENST00000239461	4	76692

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.243	0.751	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	114	149	0.764	0.00000845	1581
Missense in Polyphen		54	72.41	0.74575		768
Synonymous	-1.61	79	62.7	1.26	0.00000358	498
Loss of Function	2.37	3	11.8	0.255	7.53e-7	114

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000906	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional regulator of muscle creatine kinase (MCK) and so has a role in the establishment of diverse mesodermal muscle types. The protein binds to an A/T-rich element in the muscle creatine enhancer (By similarity). {ECO:0000250}.
• Disease: DISEASE: Agnathia-otocephaly complex (AGOTC) [MIM:202650]: A rare condition characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. The disorder is almost always lethal. {ECO:0000269|PubMed:21294718}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.203

Intolerance Scores

• loftool: 0.0691
• rvis_EVS: 0.28
• rvis_percentile_EVS: 71.27

Haploinsufficiency Scores

• pHI: 0.856
• hipred: Y
• hipred_score: 0.837
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prrx1
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; 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); vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); hearing/vestibular/ear phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype

Zebrafish Information Network

• Gene name: prrx1a
• Affected structure: atrium
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;positive regulation of mesenchymal cell proliferation;embryonic limb morphogenesis;inner ear morphogenesis;middle ear morphogenesis;positive regulation of smoothened signaling pathway;positive regulation of transcription by RNA polymerase II;neuron fate determination;embryonic cranial skeleton morphogenesis;artery morphogenesis;cartilage development;roof of mouth development;regulation of neuron projection regeneration;neuronal stem cell population maintenance
• Cellular component: nucleoplasm;cytosol
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;transcription coactivator activity;HMG box domain binding