Human Gene Module / Chromosome X / NEXMIF

NEXMIFneurite extension and migration factor

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
5 / 19
Rare Variants / Common Variants
36 / 0
Aliases
NEXMIF, KIAA2022,  KIDLIA,  MRX98,  XPN
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
Xq13.3
Associated Disorders
EPS, EP, ID, ASD, DD/NDD
Relevance to Autism

Maternally-inherited variants affecting the NEXMIF gene have been identified in male probands presenting with intellectual disability and autistic features (Cantagrel et al., 2004; Van Maldergem et al., 2013).

Molecular 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).

Reports related to NEXMIF (19 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males. Cantagrel V , et al. (2004) No -
2 Support Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders. Lim ET , et al. (2013) Yes -
3 Recent Recommendation Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth. Van Maldergem L , et al. (2013) No ASD
4 Recent Recommendation XLMR protein related to neurite extension (Xpn/KIAA2022) regulates cell-cell and cell-matrix adhesion and migration. Magome T , et al. (2013) No -
5 Support The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
6 Support A duplication of the whole KIAA2022 gene validates the gene role in the pathogenesis of intellectual disability and autism. Charzewska A , et al. (2014) Yes -
7 Support Delineation of the KIAA2022 mutation phenotype: two patients with X-linked intellectual disability and distinctive features. Kuroda Y , et al. (2015) No Hypotonia, distinctive facial dysmorphisms
8 Support X-linked intellectual disability related genes disrupted by balanced X-autosome translocations. Moyss-Oliveira M , et al. (2015) Yes -
9 Support KIAA2022 nonsense mutation in a symptomatic female. Farach LS and Northrup H (2015) No Autistic behavior, microcephaly, short stature
10 Recent Recommendation De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy. de Lange IM , et al. (2016) No ASD or autistic features
11 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Lelieveld SH , et al. (2016) No -
12 Support De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females. Webster R , et al. (2016) No -
13 Recent Recommendation The X-Linked Autism Protein KIAA2022/KIDLIA Regulates Neurite Outgrowth via N-Cadherin and -Catenin Signaling. Gilbert J and Man HY (2016) No -
14 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
15 Support Genomic diagnosis for children with intellectual disability and/or developmental delay. Bowling KM , et al. (2017) No -
16 Support High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. Hamdan FF , et al. (2017) No DD/ID
17 Support Clinical spectrum of KIAA2022 pathogenic variants in males: Case report of two boys with KIAA2022 pathogenic variants and review of the literature. Lorenzo M , et al. (2018) No Epilepsy/seizures
18 Support Novel NEXMIF pathogenic variant in a boy with severe autistic features, intellectual disability, and epilepsy, and his mildly affected mother. Lambert N , et al. (2018) No Autistic features
19 Support Breakpoint mapping at nucleotide resolution in X-autosome balanced translocations associated with clinical phenotypes. Moyss-Oliveira M , et al. (2019) No Microcephaly, short stature
Rare Variants   (36)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 27358180 de Lange IM , et al. (2016)
- - translocation De novo - - 26290131 Moyss-Oliveira M , et al. (2015)
- - translocation De novo - - 30700833 Moyss-Oliveira M , et al. (2019)
c.937C>T p.Arg313Ter stop_gained De novo - - 27568816 Webster R , et al. (2016)
c.2707G>T p.Glu903Ter stop_gained De novo - - 29693785 Lorenzo M , et al. (2018)
c.438C>A p.Cys146Ter stop_gained De novo - - 27358180 de Lange IM , et al. (2016)
c.652C>T p.Arg218Ter stop_gained De novo - - 27358180 de Lange IM , et al. (2016)
c.952C>T p.Gln318Ter stop_gained De novo - - 27358180 de Lange IM , et al. (2016)
c.964C>T p.Arg322Ter stop_gained De novo - - 27358180 de Lange IM , et al. (2016)
c.1441C>T p.Arg481Ter stop_gained De novo - - 27358180 de Lange IM , et al. (2016)
c.1882C>T p.Arg628Ter stop_gained De novo - - 27358180 de Lange IM , et al. (2016)
c.2707G>T p.Glu903Ter stop_gained De novo - - 27479843 Lelieveld SH , et al. (2016)
c.4411C>T p.Gln1471Ter stop_gained Unknown - Unknown 23352160 Lim ET , et al. (2013)
c.964C>T p.Arg322Ter stop_gained De novo - Simplex 25900396 Kuroda Y , et al. (2015)
c.2113C>T p.Gln705Ter stop_gained De novo - Simplex 25900396 Kuroda Y , et al. (2015)
- - inversion Familial Maternal Multi-generational 15466006 Cantagrel V , et al. (2004)
- - copy_number_gain Familial Maternal Simplex 23615299 Van Maldergem L , et al. (2013)
c.652C>T p.Arg218Ter stop_gained Unknown - Multiplex 29693785 Lorenzo M , et al. (2018)
c.2042del p.Gly681fs frameshift_variant De novo - - 27358180 de Lange IM , et al. (2016)
c.4185del p.Lys1396fs frameshift_variant De novo - - 27358180 de Lange IM , et al. (2016)
c.964C>T p.Arg322Ter stop_gained De novo - Simplex 26576034 Farach LS and Northrup H (2015)
c.422delA p.Gln141ArgfsTer7 frameshift_variant De novo - - 27568816 Webster R , et al. (2016)
c.625dupC p.Leu209ProfsTer3 frameshift_variant De novo - - 27568816 Webster R , et al. (2016)
c.3402C>A p.His1134Gln missense_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
- - copy_number_gain Familial Maternal Multi-generational 25394356 Charzewska A , et al. (2014)
c.2725del p.Ala909ProfsTer13 frameshift_variant De novo - - 27358180 de Lange IM , et al. (2016)
c.1582delA p.Arg528GlufsTer4 frameshift_variant De novo - - 27358180 de Lange IM , et al. (2016)
c.2999_3000delCT p.Ser1000Cysfs frameshift_variant De novo - - 28554332 Bowling KM , et al. (2017)
c.3596_3597insA p.Lys1199Asnfs frameshift_variant De novo - - 27358180 de Lange IM , et al. (2016)
c.2772_2773insTTTC p.Glu925fs frameshift_variant Unknown - Simplex 28263302 C Yuen RK , et al. (2017)
c.2935_2936insTTTCC p.Gln979fs frameshift_variant De novo - Simplex 29100083 Hamdan FF , et al. (2017)
c.2201_2202delAA p.Lys734SerfsTer24 frameshift_variant De novo - - 27358180 de Lange IM , et al. (2016)
c.3053_3066del14 p.Gly1018AspfsTer2 frameshift_variant De novo - - 27358180 de Lange IM , et al. (2016)
c.3470C>A p.Ser1157Ter stop_gained Familial Maternal Multi-generational 29717186 Lambert N , et al. (2018)
c.186delC p.Arg62GlufsTer22 frameshift_variant Familial Maternal Multi-generational 23615299 Van Maldergem L , et al. (2013)
c.3597dupA p.Ser1200TyrfsTer5 frameshift_variant Familial Maternal Multi-generational 23615299 Van Maldergem L , et al. (2013)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2018
3.3

Initial score established: 3.3

Description

3

CNVs associated with NEXMIF(1 CNVs)
Xq13.3 10 Deletion 14  /  29
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