SLC9A9

solute carrier family 9 member A9, the group of Solute carrier family 9

Basic information

Region (hg38): 3:143265222-143848485

Links

ENSG00000181804 ∙ NCBI:285195 ∙ OMIM:608396 ∙ HGNC:20653 ∙ Uniprot:Q8IVB4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism, susceptibility to, 16 (Limited), mode of inheritance: AD
• autism spectrum disorder (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autism susceptibility 16	AD	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	Neurologic	18621663

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC9A9 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC9A9 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	12	9	22
missense			42	2	2	46
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1	1	2	4
non coding				2	1	3
Total	0	0	47	16	12

Variants in SLC9A9

This is a list of pathogenic ClinVar variants found in the SLC9A9 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-143266748-T-C		not specified	Uncertain significance (Mar 25, 2024)
3-143266761-C-T		not specified	Uncertain significance (Apr 25, 2022)
3-143266775-T-C		not specified	Uncertain significance (Feb 14, 2023)
3-143266788-T-C		not specified	Uncertain significance (Oct 26, 2022)
3-143266803-G-A		not specified	Uncertain significance (Jun 17, 2024)
3-143266816-G-A			Benign (Dec 01, 2023)
3-143266832-G-T		not specified	Conflicting classifications of pathogenicity (Mar 01, 2024)
3-143266839-G-A		not specified	Uncertain significance (Nov 06, 2023)
3-143266874-A-G		not specified	Uncertain significance (Sep 07, 2022)
3-143266898-A-G			Uncertain significance (Mar 26, 2017)
3-143266910-T-C		not specified	Uncertain significance (Jun 24, 2022)
3-143266921-T-C		SLC9A9-related disorder	Likely benign (Nov 01, 2023)
3-143268879-T-A		not specified	Uncertain significance (Sep 26, 2022)
3-143268911-C-T		SLC9A9-related disorder	Likely benign (Jun 06, 2019)
3-143268918-C-T		not specified	Uncertain significance (Mar 28, 2024)
3-143268919-A-G		not specified	Uncertain significance (Nov 08, 2021)
3-143268928-G-A		not specified	Uncertain significance (Apr 26, 2023)
3-143268944-C-T			Likely benign (Feb 01, 2024)
3-143268951-C-T		not specified	Uncertain significance (Dec 16, 2023)
3-143268967-T-C			Benign (Dec 31, 2019)
3-143363474-C-G		not specified	Likely benign (Feb 28, 2024)
3-143363487-T-G		not specified	Uncertain significance (Mar 21, 2024)
3-143363495-G-C		not specified	Uncertain significance (Sep 27, 2022)
3-143363513-G-A		SLC9A9-related disorder	Likely benign (May 31, 2019)
3-143363514-A-G		not specified	Uncertain significance (Apr 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC9A9	protein_coding	protein_coding	ENST00000316549	16	583310

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.33e-12	0.808	125655	0	93	125748	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.247	360	347	1.04	0.0000178	4238
Missense in Polyphen		143	153.48	0.93175		1817
Synonymous	-1.39	154	134	1.15	0.00000790	1230
Loss of Function	1.77	23	34.1	0.674	0.00000176	402

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000684	0.000684
Ashkenazi Jewish	0.00159	0.00159
East Asian	0.00114	0.000925
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000300	0.000299
Middle Eastern	0.00114	0.000925
South Asian	0.000196	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act in electroneutral exchange of protons for Na(+) across membranes. Involved in the effusion of Golgi luminal H(+) in exchange for cytosolic cations. Involved in organelle ion homeostasis by contributing to the maintenance of the unique acidic pH values of the Golgi and post-Golgi compartments in the cell. {ECO:0000269|PubMed:15522866}.
• Disease: DISEASE: Autism 16 (AUTS16) [MIM:613410]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. AUTS16 can be associated with epilepsy. {ECO:0000269|PubMed:18621663}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Sodium/Proton exchangers;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules (Consensus)

Intolerance Scores

• loftool: 0.884
• rvis_EVS: -0.86
• rvis_percentile_EVS: 10.89

Haploinsufficiency Scores

• pHI: 0.233
• hipred: N
• hipred_score: 0.441
• ghis: 0.482

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.280

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc9a9
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: ion transport;regulation of intracellular pH;potassium ion transmembrane transport;sodium ion import across plasma membrane;proton transmembrane transport
• Cellular component: plasma membrane;integral component of membrane;late endosome membrane;recycling endosome
• Molecular function: protein binding;sodium:proton antiporter activity;potassium:proton antiporter activity