SLC9A1

solute carrier family 9 member A1, the group of Protein phosphatase 1 regulatory subunits|Solute carrier family 9

Basic information

Region (hg38): 1:27098809-27166981

Previous symbols: [ "APNH", "NHE1", "NHE-1" ]

Links

ENSG00000090020 ∙ NCBI:6548 ∙ OMIM:107310 ∙ HGNC:11071 ∙ Uniprot:P19634 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Lichtenstein-Knorr syndrome (Moderate), mode of inheritance: AR
• Lichtenstein-Knorr syndrome (Limited), mode of inheritance: AR
• Lichtenstein-Knorr syndrome (Supportive), mode of inheritance: AR
• Lichtenstein-Knorr syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 19 (Lichtenstein-Knorr syndrome)	AR	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	Audiologic/Otolaryngologic; Neurologic	25205112

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC9A1 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC9A1 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	57	7	65
missense		1	68	1	1	71
nonsense						0
start loss						0
frameshift	1	1	1			3
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)			2			2
splice region			2	9	2	13
non coding			1	12	4	17
Total	1	2	74	70	13

Variants in SLC9A1

This is a list of pathogenic ClinVar variants found in the SLC9A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-27100305-T-C		Lichtenstein-Knorr syndrome	Benign (Jul 15, 2021)
1-27100335-C-T		not specified	Uncertain significance (Apr 27, 2024)
1-27100354-G-A			Uncertain significance (May 05, 2023)
1-27100356-G-A			Uncertain significance (Jan 10, 2023)
1-27100358-G-C			Likely benign (Oct 18, 2022)
1-27100362-G-A			Uncertain significance (Sep 02, 2022)
1-27100362-G-C		SLC9A1-related disorder	Uncertain significance (Jul 10, 2023)
1-27100384-T-C		not specified	Uncertain significance (Aug 04, 2023)
1-27100398-G-A			Uncertain significance (Aug 13, 2022)
1-27100403-G-T			Uncertain significance (Jan 13, 2022)
1-27100412-C-T			Likely benign (Dec 07, 2022)
1-27100436-T-G		SLC9A1-related disorder	Likely benign (Nov 01, 2022)
1-27100453-C-T		not specified	Uncertain significance (Aug 07, 2024)
1-27100462-G-A			Uncertain significance (Aug 01, 2022)
1-27100480-C-T		not specified	Uncertain significance (Sep 05, 2024)
1-27100481-G-A			Likely benign (Dec 18, 2023)
1-27100483-C-T		not specified	Uncertain significance (Dec 06, 2021)
1-27100484-G-A			Likely benign (Aug 25, 2022)
1-27100489-C-G		not specified	Uncertain significance (Dec 19, 2023)
1-27100489-C-T		not specified	Uncertain significance (Jan 08, 2024)
1-27100496-C-T			Benign (Dec 11, 2023)
1-27100518-C-T		not specified	Uncertain significance (Feb 03, 2022)
1-27100519-G-A		not specified	Uncertain significance (Feb 10, 2022)
1-27100528-C-G			Uncertain significance (Jul 28, 2022)
1-27100547-C-G		not specified	Uncertain significance (Feb 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC9A1	protein_coding	protein_coding	ENST00000263980	12	68167

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.790	0.210	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.55	292	520	0.562	0.0000342	5301
Missense in Polyphen		63	188.83	0.33363		2028
Synonymous	1.66	204	237	0.862	0.0000175	1724
Loss of Function	4.22	6	31.6	0.190	0.00000179	334

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.000202	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000170	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. {ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:8901634}.
• Disease: DISEASE: Lichtenstein-Knorr syndrome (LIKNS) [MIM:616291]: An autosomal recessive neurologic disorder characterized by progressive cerebellar ataxia and severe progressive sensorineural hearing loss. {ECO:0000269|PubMed:25205112}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Bile secretion - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Osteoclast Signaling;G Protein Signaling Pathways;Regulation of Actin Cytoskeleton;Hyaluronan uptake and degradation;Hyaluronan metabolism;Metabolism of carbohydrates;Glycosaminoglycan metabolism;Sodium/Proton exchangers;Metabolism;Transport of inorganic cations/anions and amino acids/oligopeptides;SLC-mediated transmembrane transport;Transport of small molecules;ErbB1 downstream signaling;Signaling mediated by p38-alpha and p38-beta;Endothelins;RhoA signaling pathway (Consensus)

Recessive Scores

• pRec: 0.460

Intolerance Scores

• loftool: 0.387
• rvis_EVS: -1.62
• rvis_percentile_EVS: 2.93

Haploinsufficiency Scores

• pHI: 0.417
• hipred: Y
• hipred_score: 0.729
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.904

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc9a1
• Phenotype: endocrine/exocrine gland phenotype; 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; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); digestive/alimentary phenotype

Gene ontology

• Biological process: ion transport;cellular sodium ion homeostasis;regulation of pH;response to acidic pH;positive regulation of cardiac muscle hypertrophy;regulation of cardiac muscle contraction by calcium ion signaling;cell migration;maintenance of cell polarity;hyaluronan catabolic process;positive regulation of cell growth;cellular response to insulin stimulus;positive regulation of mitochondrial membrane permeability;response to muscle stretch;sodium ion export across plasma membrane;positive regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of action potential;positive regulation of transcription by RNA polymerase II;protein complex oligomerization;regulation of intracellular pH;regulation of stress fiber assembly;regulation of focal adhesion assembly;regulation of sensory perception of pain;cardiac muscle cell differentiation;cellular response to cold;positive regulation of calcineurin-NFAT signaling cascade;neuron death;cellular response to antibiotic;cellular response to electrical stimulus;cellular response to mechanical stimulus;cellular response to hypoxia;cellular response to acidic pH;potassium ion transmembrane transport;cellular response to epinephrine stimulus;cardiac muscle cell contraction;regulation of cardiac muscle cell membrane potential;regulation of the force of heart contraction by cardiac conduction;sodium ion import across plasma membrane;positive regulation of the force of heart contraction;proton transmembrane transport;positive regulation of calcium:sodium antiporter activity
• Cellular component: nucleoplasm;cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane;focal adhesion;cell surface;intercalated disc;integral component of membrane;basolateral plasma membrane;apical plasma membrane;lamellipodium;T-tubule;membrane raft;perinuclear region of cytoplasm;extracellular exosome;cation-transporting ATPase complex
• Molecular function: protein binding;calmodulin binding;phosphatidylinositol-4,5-bisphosphate binding;solute:proton antiporter activity;sodium:proton antiporter activity;potassium:proton antiporter activity;protein phosphatase 2B binding;protein binding, bridging;protein-containing complex scaffold activity;calcium-dependent protein binding;sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential