ALX3

ALX homeobox 3, the group of PRD class homeoboxes and pseudogenes

Basic information

Region (hg38): 1:110059870-110070672

Previous symbols: [ "FND" ]

Links

ENSG00000156150 ∙ NCBI:257 ∙ OMIM:606014 ∙ HGNC:449 ∙ Uniprot:O95076 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• frontorhiny (Definitive), mode of inheritance: AR
• frontorhiny (Strong), mode of inheritance: AR
• frontorhiny (Supportive), mode of inheritance: AR
• frontorhiny (Strong), mode of inheritance: AR
• frontorhiny (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Frontonasal dysplasia 1	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	17963218; 19409524; 22106187

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALX3 gene.

• Frontorhiny (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALX3 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				8	2	10
missense			34	2		36
nonsense	2					2
start loss						0
frameshift		1				1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					6	6
Total	2	1	35	10	8

Variants in ALX3

This is a list of pathogenic ClinVar variants found in the ALX3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-110060664-A-AGGTGCTTCCTCCGTGGTGTCCAGGCAGG			Benign (Nov 10, 2018)
1-110060761-G-A		Inborn genetic diseases	Uncertain significance (Mar 28, 2023)
1-110060767-T-G		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
1-110060772-C-G		Inborn genetic diseases	Uncertain significance (Aug 10, 2023)
1-110060777-C-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
1-110060778-C-G		Inborn genetic diseases	Uncertain significance (Mar 20, 2024)
1-110060790-G-A		ALX3-related disorder	Likely benign (Jun 28, 2019)
1-110060806-T-C		Inborn genetic diseases	Uncertain significance (Jan 24, 2024)
1-110060850-G-A			Benign (Nov 15, 2023)
1-110060878-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2024)
1-110060889-C-T			Likely benign (Oct 08, 2022)
1-110060896-G-C		Inborn genetic diseases	Uncertain significance (Oct 30, 2024)
1-110060903-G-A		Inborn genetic diseases	Uncertain significance (Nov 04, 2020)
1-110060987-G-A		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
1-110061016-G-A		Inborn genetic diseases	Uncertain significance (Aug 04, 2024)
1-110061017-G-C		not specified	Benign/Likely benign (Nov 01, 2024)
1-110061027-CAG-C		Frontorhiny	Likely pathogenic (Aug 03, 2016)
1-110061454-C-T		Inborn genetic diseases	Uncertain significance (Apr 29, 2021)
1-110061464-C-T		Inborn genetic diseases	Uncertain significance (Oct 29, 2021)
1-110061469-A-C		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
1-110061475-T-C		Inborn genetic diseases	Uncertain significance (Jul 14, 2022)
1-110061496-C-T		Inborn genetic diseases • Frontorhiny	Conflicting classifications of pathogenicity (Jun 27, 2024)
1-110061516-A-G			Likely benign (Mar 29, 2018)
1-110061527-G-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
1-110061531-C-T		not specified	Benign/Likely benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALX3	protein_coding	protein_coding	ENST00000369792	4	10707

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0191	0.907	125740	0	7	125747	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.446	151	167	0.903	0.0000103	2178
Missense in Polyphen		54	78.396	0.68881		805
Synonymous	0.475	63	68.0	0.927	0.00000385	752
Loss of Function	1.51	4	8.87	0.451	4.64e-7	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000355	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional regulator with a possible role in patterning of mesoderm during development. {ECO:0000250}.
• Disease: DISEASE: Frontonasal dysplasia 1 (FND1) [MIM:136760]: 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:19409524}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0999

Intolerance Scores

• loftool: 0.150
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.75

Haploinsufficiency Scores

• pHI: 0.521
• hipred: N
• hipred_score: 0.410
• ghis: 0.626

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.467

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alx3
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; 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); reproductive system phenotype; vision/eye phenotype; digestive/alimentary 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; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;pattern specification process;embryonic forelimb morphogenesis;embryonic hindlimb morphogenesis;regulation of apoptotic process;embryonic cranial skeleton morphogenesis
• Cellular component: nucleus
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;sequence-specific DNA binding