ALX4 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- ALX4 (HGNC:450) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- ALX homeobox 4
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- PFM2
- Alias symbols
- FPP, PFM, KIAA1788
- %HI
- 8.75(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.36(Read more about gnomAD pLI score)
- LOEUF
- 0.52(Read more about gnomAD LOEUF score)
- Cytoband
- 11p11.2
- Genomic Coordinates
-
GRCh37/hg19: chr11:44281990-44331689 NCBI Ensembl UCSC GRCh38/hg38: chr11:44260440-44310139 NCBI Ensembl UCSC - MANE Select Transcript
- NM_021926.4 ENST00000652299.1 (Read more about MANE Select)
- Function
- Transcription factor involved in skull and limb development. Plays an essential role in craniofacial development, skin and hair follicle development. {ECO:0000269|PubMed:19692347}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-30494
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
07/22/2020
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- parietal foramina 2 Monarch
HI Evidence:
-
PUBMED:
11137991
Mavrogiannis et al. (2001): 3 distinct ALX4 variants in 19 individuals from 4 families segregating parietal foramina (PFM) including those families linked to 11p region (region that includes proximal 11p deletion syndrome)were described. Family 1 nonsense variant c.418 C->T (p.Gln140Ter) that was inherited (affected IV-1 from affected father III-3); another affected paternal relative was also found to carry the variant, for a total of 2 segregations in this family. Family 2 nonsense variant c.736 C->T (p.Arg18Gln) also segregated with disease in several affected members of the family (for example, proband IV-4 inherited from III-6, II-3, I-2). However, there was also at least one individual in this family with the variant and a normal skull radiograph; this individual did go on to have two affected children (individuals III-7 and III-8). In all, this family demonstrated 6 segregations between genotype+/phenotype+ individuals. These nonsense variants were thought to completely or partially eliminate the DNA-binding homeodomain.
-
PUBMED:
11106354
Wuyts et al. (2000): Mutational analysis of the ALX4 gene in three unrelated Foramina parietalia permagna (FPP) families without MSX2 variants were analyzed. Family 1 identified a c.504delT in proband inherited from affected father. The authors noted that this variant results in a premature stop codon.
-
PUBMED:
16319823
Mavrogiannis et al. (2006): The authors discuss looked at 20 unrelated families with an established diagnosis of enlarged parietal formina (PFM) or cranum bifidum (CB), 14 were familial cases and 6 were sporadic cases. Family 10 was identified as having a c.620c->A(p.S207X). The variant was detected in all 5 affected individuals with PFM, absent or malpositioned teeth, short an broad thumbs/halluces, and mild facial dysmorphism. Three siblings, the father and paternal grandfather were tested. Family 11 was identified as having frameshifting deletion c.385_394del (p.C129PfsX49). The unaffected parents were not tested in family 11.
HI Evidence Comments:
PMID: 29215649 Lee et al. (2018) designed a 20 gene panel based on genes associated with craniosynostosis through retrospective testing of an Australian and New Zealand cohort of 233 individuals.Two ALX4 gene variants were identified c.94del (p.Ser32Argfs*149) seen in a patient with parieto-occipital skull defect and a c.712T>G (p.Tyr238Asp).
Parietal foramina also occur as part of the Potocki-Shaffer syndrome ( OMIM: 601224), a contiguous gene syndrome caused by a deletion on chromosome 11p11.2 that includes the ALX4 gene.
Biallelic ALX4 variants (autosomal recessive) cause frontonasal dysplasia-2 (FND2; 613451), which is also associated with parietal foramina but has more severe frontonasal defects.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No evidence found supporting or refuting an association between duplications of the ALX4 gene and a specific phenotype.
Genomic View
Select assembly:
(NC_000011.9)
(NC_000011.10)