NEXMIF |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- NEXMIF (HGNC:29433) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- neurite extension and migration factor
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- KIAA2022
- Alias symbols
- XPN, MRX98, KIDLIA
- %HI
- 29.47(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.2(Read more about gnomAD LOEUF score)
- Cytoband
- Xq13.3
- Genomic Coordinates
-
GRCh37/hg19: chrX:73952691-74145287 NCBI Ensembl UCSC GRCh38/hg38: chrX:74732856-74925452 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001008537.3 ENST00000055682.12 (Read more about MANE Select)
- Function
- Involved in neurite outgrowth by regulating cell-cell adhesion via the N-cadherin signaling pathway. May act by regulating expression of protein-coding genes, such as N-cadherins and integrin beta-1 (ITGB1). {ECO:0000250|UniProtKB:D3ZGX1}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- X-linked intellectual disability, Cantagrel type Monarch
-
PUBMED:
2756881
Van Maldergem et al. (2013), studied 8 male patients (4 families) with X-linked intellectual disability and likely pathogenic mutations in the NEXMIF gene. The c.186delC and c.3597dupA NEXMIF truncating mutations were identified by X-chromosome exome sequencing, while array-CGH discovered a 70 kb microduplication encompassing NEXMIF exon 1 in the third family. All patients presented moderate-to-severe ID with autistic features and strabismus. Morphometric studies in cultured rat hippocampal neurons showed that siRNA-mediated NEXMIF knockdown resulted in marked impairment in neurite outgrowth including both the dendrites and the axons, suggesting a major role for NEXMIF in neuron development and brain function.
-
PUBMED:
27358180
De Lange et al. (2016), reports 14 female carriers of a heterozygous de novo NEXMIF mutation. A wide mutation spectrum was reported, including 6 nonesense, 6 small dels, 1 gross del and 1 small insertion. All mutations were LoF, predicted to result in a frameshift or premature stop. The patients presented a neurodevelopmental disorder characterized by intellectual disability and epilepsy. X-inactivation was found to be random in 6 patients, while one patient showed complete skewing.
-
PUBMED:
27568816
Using whole-exome sequencing, Webster et al. (2016), studied 2323 females referred for developmental delay/ID. They identified a cohort of five unrelated females with de novo predicted pathogenic variants in NEXMIF. A wide mutation spectrum was reported, including 2 nonsense,1 frameshift, 1 small del and 1 small dup. All variants were confirmed by Sanger sequencing. The core phenotypic features included ID, developmental delay, impaired language and epilepsy refractory to Treatment.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.