ALX1

ALX homeobox 1, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 12:85280220-85301784

Previous symbols: [ "CART1" ]

Links

ENSG00000180318 ∙ NCBI:8092 ∙ OMIM:601527 ∙ HGNC:1494 ∙ Uniprot:Q15699 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome (Definitive), mode of inheritance: AR
• frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome (Strong), mode of inheritance: AR
• frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome (Strong), mode of inheritance: AR
• frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome (Supportive), mode of inheritance: AR
• frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Frontonasal dysplasia 3	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	20451171

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALX1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALX1 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				7	3	10
missense			14	2	2	18
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	4	5
Total	0	1	14	10	9

Variants in ALX1

This is a list of pathogenic ClinVar variants found in the ALX1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-85280284-T-C		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
12-85280309-A-G			Benign (Jan 04, 2024)
12-85280370-A-G		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
12-85280406-T-A		Inborn genetic diseases	Uncertain significance (Sep 22, 2022)
12-85280410-T-C		not specified • Inborn genetic diseases	Uncertain significance (Mar 20, 2024)
12-85280411-G-T			Likely benign (Dec 11, 2023)
12-85280412-C-T		Frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome	Likely pathogenic (-)
12-85280443-A-G			Benign (Jan 02, 2024)
12-85280451-C-A		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
12-85280451-C-T		not specified • ALX1-related disorder	Conflicting classifications of pathogenicity (Dec 28, 2023)
12-85280452-G-T		not specified • Frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome • ALX1-related disorder	Benign/Likely benign (Dec 11, 2023)
12-85280680-C-A			Benign (May 10, 2021)
12-85283611-A-G			Benign (Jan 19, 2024)
12-85283631-A-G		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
12-85283633-G-A		Inborn genetic diseases	Uncertain significance (Sep 22, 2022)
12-85283701-T-G			Likely benign (Jun 29, 2023)
12-85283702-T-A		ALX1-related disorder	Likely benign (Dec 15, 2022)
12-85283722-A-G		Inborn genetic diseases	Uncertain significance (Mar 13, 2023)
12-85283758-C-T		not specified	Uncertain significance (Mar 10, 2017)
12-85283759-C-T			Likely benign (Nov 19, 2023)
12-85283852-A-G		ALX1-related disorder	Likely benign (Feb 22, 2021)
12-85283877-G-A		Frontonasal dysplasia - severe microphthalmia - severe facial clefting syndrome	Pathogenic (May 14, 2010)
12-85286749-A-AT			Benign (May 11, 2021)
12-85286836-T-C			Benign (Jan 19, 2024)
12-85286842-T-G			Likely benign (Aug 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALX1	protein_coding	protein_coding	ENST00000316824	4	21678

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.176	0.821	125737	0	5	125742	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0961	183	187	0.980	0.00000962	2164
Missense in Polyphen		37	44.684	0.82805		518
Synonymous	-0.249	74	71.3	1.04	0.00000374	616
Loss of Function	2.64	4	15.1	0.265	9.10e-7	152

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)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000657	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sequence-specific DNA-binding transcription factor that binds palindromic sequences within promoters and may activate or repress the transcription of a subset of genes (PubMed:9753625, PubMed:8756334). Most probably regulates the expression of genes involved in the development of mesenchyme-derived craniofacial structures. Early on in development, it plays a role in forebrain mesenchyme survival (PubMed:20451171). May also induce epithelial to mesenchymal transition (EMT) through the expression of SNAI1 (PubMed:23288509). {ECO:0000269|PubMed:20451171, ECO:0000269|PubMed:23288509, ECO:0000269|PubMed:8756334, ECO:0000269|PubMed:9753625}.
• Disease: DISEASE: Frontonasal dysplasia 3 (FND3) [MIM:613456]: The term frontonasal dysplasia describes an array of abnormalities affecting the eyes, forehead and nose and linked to midfacial dysraphia. The clinical picture is highly variable. Major findings include true ocular hypertelorism; broadening of the nasal root; median facial cleft affecting the nose and/or upper lip and palate; unilateral or bilateral clefting of the alae nasi; lack of formation of the nasal tip; anterior cranium bifidum occultum; a V-shaped or widow's peak frontal hairline. {ECO:0000269|PubMed:20451171}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.161
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.38

Haploinsufficiency Scores

• pHI: 0.654
• hipred: Y
• hipred_score: 0.783

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alx1
• Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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); limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye 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); normal phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: alx1
• Affected structure: cranial neural crest cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cartilage condensation;neural crest cell migration;neural tube closure;transcription by RNA polymerase II;multicellular organism development;anterior/posterior pattern specification;positive regulation of epithelial to mesenchymal transition;embryonic limb morphogenesis;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;embryonic skeletal system morphogenesis;roof of mouth development
• Cellular component: nucleus;nucleoplasm;transcription factor complex;Golgi apparatus;nuclear body
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;protein homodimerization activity;protein heterodimerization activity