SLC9A6

solute carrier family 9 member A6, the group of Solute carrier family 9

Basic information

Region (hg38): X:135973841-136047269

Links

ENSG00000198689 ∙ NCBI:10479 ∙ OMIM:300231 ∙ HGNC:11079 ∙ Uniprot:Q92581 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Christianson syndrome (Supportive), mode of inheritance: XL
• Christianson syndrome (Definitive), mode of inheritance: XL
• Christianson syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked syndromic, Christianson type	XL	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; Neurologic	10528855; 18342287; 19377476; 20949524; 22931061; 25044251
In addition to other features, retinitis pigmentosa has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC9A6 gene.

• Christianson_syndrome (401 variants)
• not_provided (187 variants)
• not_specified (49 variants)
• Inborn_genetic_diseases (43 variants)
• SLC9A6-related_disorder (11 variants)
• Intellectual_disability (8 variants)
• Seizure (2 variants)
• Allergy (1 variants)
• Motor_delay (1 variants)
• EEG_with_generalized_slow_activity (1 variants)
• Gastrostomy_tube_feeding_in_infancy (1 variants)
• Microcephaly (1 variants)
• Recurrent_respiratory_infections (1 variants)
• Delayed_speech_and_language_development (1 variants)
• Sleep_abnormality (1 variants)
• Scoliosis (1 variants)
• Amblyopia (1 variants)
• Open_mouth (1 variants)
• Obesity (1 variants)
• Neurodevelopmental_disorder (1 variants)
• History_of_neurodevelopmental_disorder (1 variants)
• Strabismus (1 variants)
• Leukodystrophy (1 variants)
• Global_developmental_delay (1 variants)
• Hypermetropia (1 variants)
• Short_stature (1 variants)
• Astigmatism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC9A6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001379110.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	102	8	113
missense	2	9	182	19	4	216
nonsense	8	1	1			10
start loss						0
frameshift	18	7	2	1		28
splice donor/acceptor (+/-2bp)	5	6	2	1		14
Total	33	23	190	123	12

Highest pathogenic variant AF is 0.00000902812

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC9A6	protein_coding	protein_coding	ENST00000370695	16	61826

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00167	125611	1	0	125612	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.95	137	275	0.499	0.0000202	4591
Missense in Polyphen		33	123.01	0.26827		2116
Synonymous	0.359	100	105	0.955	0.00000791	1406
Loss of Function	4.26	1	23.1	0.0434	0.00000171	379

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000122	0.00000881
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Electroneutral exchange of protons for Na(+) and K(+) across the early and recycling endosome membranes. Contributes to calcium homeostasis.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Sodium/Proton exchangers;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.448
• hipred: Y
• hipred_score: 0.740
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.657

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc9a6
• Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system 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); hematopoietic system 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)

Gene ontology

• Biological process: ion transport;brain-derived neurotrophic factor receptor signaling pathway;axon extension;neuron projection morphogenesis;synapse organization;regulation of neurotrophin TRK receptor signaling pathway;regulation of intracellular pH;dendritic spine development;potassium ion transmembrane transport;dendrite extension;sodium ion import across plasma membrane;proton transmembrane transport
• Cellular component: mitochondrion;late endosome;endoplasmic reticulum membrane;plasma membrane;integral component of membrane;dendrite;early endosome membrane;intracellular membrane-bounded organelle;axon terminus;axonal spine;recycling endosome;recycling endosome membrane
• Molecular function: sodium:proton antiporter activity;potassium:proton antiporter activity