MSX1
msh homeobox 1, the group of NKL subclass homeoboxes and pseudogenes
Basic information
Region (hg38): 4:4859665-4863936
Previous symbols: [ "HOX7" ]
Links
Phenotypes
GenCC
Source:
- orofacial cleft 5 (Definitive), mode of inheritance: AD
- tooth and nail syndrome (Supportive), mode of inheritance: AD
- tooth agenesis (Supportive), mode of inheritance: AD
- tooth agenesis, selective, 1 (Strong), mode of inheritance: AD
- tooth and nail syndrome (Limited), mode of inheritance: AD
- tooth agenesis, selective, 1 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Orofacial cleft 5; Tooth agenesis, selective, 1, with/without orofacial cleft; Witkop syndrome | AD | 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 | Craniofacial; Dental; Dermatologic | 8696335; 10742093; 11369996; 12097313; 12807959; 15264286; 15354328; 16327884; 16498076; 16868654; 16932841; 18374898; 19346736; 21297014; 21626677; 22297032 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hypoplastic_enamel-onycholysis-hypohidrosis_syndrome (67 variants)
- Inborn_genetic_diseases (53 variants)
- not_provided (17 variants)
- Tooth_agenesis,_selective,_1 (14 variants)
- MSX1-related_disorder (13 variants)
- Orofacial_cleft_5 (6 variants)
- MSX1-related_selective_tooth_agenesis_with_or_without_orofacial_cleft (1 variants)
- Craniosynostosis_syndrome (1 variants)
- not_specified (1 variants)
- Oligodontia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MSX1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002448.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 16 | 17 | ||||
| missense | 81 | 12 | 104 | |||
| nonsense | 10 | |||||
| start loss | 0 | |||||
| frameshift | 11 | 13 | ||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 24 | 4 | 84 | 28 | 5 |
Highest pathogenic variant AF is 0.0000260362
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MSX1 | protein_coding | protein_coding | ENST00000382723 | 2 | 4271 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.165 | 0.778 | 124097 | 0 | 3 | 124100 | 0.0000121 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.278 | 158 | 168 | 0.940 | 0.0000100 | 1870 |
| Missense in Polyphen | 40 | 66.307 | 0.60325 | 690 | ||
| Synonymous | -1.45 | 97 | 80.5 | 1.21 | 0.00000492 | 669 |
| Loss of Function | 1.57 | 2 | 6.22 | 0.321 | 2.65e-7 | 80 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000644 | 0.0000640 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000196 | 0.0000179 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as a transcriptional repressor. May play a role in limb-pattern formation. Acts in cranofacial development and specifically in odontogenesis. Expression in the developing nail bed mesenchyme is important for nail plate thickness and integrity. {ECO:0000269|PubMed:11369996, ECO:0000269|PubMed:12807959}.;
- Disease
- DISEASE: Tooth agenesis, selective, 1 (STHAG1) [MIM:106600]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG1 can be associated with orofacial cleft in some patients. {ECO:0000269|PubMed:12097313, ECO:0000269|PubMed:8696335}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=MSX1 is deleted in some patients with Wolf- Hirschhorn syndrome (WHS). WHS results from sub-telomeric deletions in the short arm of chromosome 4. {ECO:0000305|PubMed:1969845}.; DISEASE: Ectodermal dysplasia 3, Witkop type (ECTD3) [MIM:189500]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD3 is characterized by abnormalities largely limited largely to teeth (some of which are missing) and nails (which are poorly formed early in life, especially toenails). This condition is distinguished from anhidrotic ectodermal dysplasia by autosomal dominant inheritance and little involvement of hair and sweat glands. The teeth are not as severely affected. {ECO:0000269|PubMed:11369996}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Non-syndromic orofacial cleft 5 (OFC5) [MIM:608874]: A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. {ECO:0000269|PubMed:12807959}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- HTLV-I infection - Homo sapiens (human);Neural Crest Differentiation;Dopaminergic Neurogenesis;Prader-Willi and Angelman Syndrome
(Consensus)
Recessive Scores
- pRec
- 0.606
Haploinsufficiency Scores
- pHI
- 0.831
- hipred
- Y
- hipred_score
- 0.735
- ghis
- 0.463
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Msx1
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear 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); 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; skeleton phenotype; vision/eye phenotype;
Zebrafish Information Network
- Gene name
- msx1a
- Affected structure
- ceratobranchial cartilage
- Phenotype tag
- abnormal
- Phenotype quality
- shortened
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;cell morphogenesis;in utero embryonic development;epithelial to mesenchymal transition involved in endocardial cushion formation;muscle organ development;negative regulation of cell population proliferation;anterior/posterior pattern specification;mesenchymal cell proliferation;pituitary gland development;signal transduction involved in regulation of gene expression;negative regulation of cell growth;positive regulation of BMP signaling pathway;midbrain development;protein localization to nucleus;embryonic forelimb morphogenesis;embryonic hindlimb morphogenesis;embryonic nail plate morphogenesis;middle ear morphogenesis;odontogenesis of dentin-containing tooth;regulation of odontogenesis;negative regulation of apoptotic process;positive regulation of DNA damage response, signal transduction by p53 class mediator;positive regulation of transcription by RNA polymerase II;embryonic morphogenesis;stem cell differentiation;protein stabilization;negative regulation of striated muscle cell differentiation;roof of mouth development;face morphogenesis;bone morphogenesis;cartilage morphogenesis;mammary gland epithelium development;BMP signaling pathway involved in heart development;cellular response to nicotine;activation of meiosis;positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator;negative regulation of transcription regulatory region DNA binding;positive regulation of mesenchymal cell apoptotic process
- Cellular component
- nucleus;nucleoplasm
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;p53 binding;enhancer binding