Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

SLC9A6

HGNC:11079 (protein-coding gene)

solute carrier family 9 member A6

Unique Cases:
29
Disorders:
ID, ASD, EP, CP
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
SLC9A6 is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Endosomal Na(+), K(+)/H(+) antiporter (PubMed:15522866, PubMed:28635961, PubMed:31676550, PubMed:32277048). Mediates the electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) or K(+). By facilitating proton efflux, SLC9A6 counteracts the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal acidification. Responsible for alkalizing and maintaining the endosomal pH, and consequently in, e.g., endosome maturation and trafficking of recycling endosomal cargo (PubMed:1... (Source: Uniprot)
Previous symbols
No previous symbols
Alias symbols
NHE6, KIAA0267, NHE-6
Chromosomal Location
Xq26.3
Genomic Coordinates
GRCh37:chrX:135067583-135129428
GRCh38:chrX:135974596-136047269
Associated Disorders
Intellectual Disability, Autism, Epilepsy, Cerebral Palsy

Predictive Scores:

HI Score (Decipher)

22.85

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.21

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

Definitive

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Definitive3 Supportive1

Publications:

Fung CW et. al., Gene panel analysis for nonsyndromic cryptogenic neonatal/infantile epileptic encephalopathy., Epilepsia Open, 2017
Tan CA et. al., Characterization of patients referred for non-specific intellectual disability testing: the importance of autosomal genes for diagnosis., Clin Genet, 2016
Tzschach A et. al., Next-generation sequencing in X-linked intellectual disability., Eur J Hum Genet, 2015
Trump N et. al., Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis., J Med Genet, 2016
Boonsawat P et. al., Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly., Genet Med, 2019
Deciphering Developmental Disorders Study. et. al., Large-scale discovery of novel genetic causes of developmental disorders., Nature, 2015
Redin C et. al., Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing., J Med Genet, 2014
Gilfillan GD et. al., SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome., Am J Hum Genet, 2008
Yang L et. al., Clinical and genetic spectrum of a large cohort of children with epilepsy in China., Genet Med, 2019
Riess A et. al., Novel SLC9A6 mutations in two families with Christianson syndrome., Clin Genet, 2013
Masurel-Paulet A et. al., A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome., Am J Med Genet A, 2016
Schroer RJ et. al., Natural history of Christianson syndrome., Am J Med Genet A, 2010
Takahashi Y et. al., A loss-of-function mutation in the SLC9A6 gene causes X-linked mental retardation resembling Angelman syndrome., Am J Med Genet B Neuropsychiatr Genet, 2011
Fernández-Marmiesse A et. al., Rare Variants in 48 Genes Account for 42% of Cases of Epilepsy With or Without Neurodevelopmental Delay in 246 Pediatric Patients., Front Neurosci, 2019
Ko A et. al., Targeted gene panel and genotype-phenotype correlation in children with developmental and epileptic encephalopathy., Epilepsy Res, 2018
McSherry M et. al., Identification of candidate gene FAM183A and novel pathogenic variants in known genes: High genetic heterogeneity for autosomal recessive intellectual disability., PLoS One, 2018
Grozeva D et. al., Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability., Hum Mutat, 2015
Schuurs-Hoeijmakers JH et. al., Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing., J Med Genet, 2013
Zanni G et. al., A novel mutation in the endosomal Na+/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES)., Epilepsy Res, 2014
Mignot C et. al., Novel mutation in SLC9A6 gene in a patient with Christianson syndrome and retinitis pigmentosum., Brain Dev, 2013
Zech M et. al., Monogenic variants in dystonia: an exome-wide sequencing study., Lancet Neurol, 2020
Zhao X et. al., Genetic analysis and identification of novel variations in Chinese patients with pediatric epilepsy by whole-exome sequencing., Neurol Sci, 2022

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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