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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SLC9A7
solute carrier family 9 member A7
Chromosome X · Xp11.3|Xp11.3
NCBI Gene: 84679Ensembl: ENSG00000065923.10HGNC: HGNC:17123UniProt: A0A087WXD1
24PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsodium:proton antiporter activitypotassium:proton antiporter activityGolgi lumen acidificationX-linked syndromic intellectual disabilityintellectual developmental disorder, X-linked 108non-syndromic X-linked intellectual disabilityX-linked non-syndromic intellectual disability
✦AI Summary

SLC9A7 is a Golgi-localized Na+/K+/H+ antiporter that mediates electroneutral influx of sodium or potassium in exchange for protons, primarily functioning in the trans-Golgi network and post-Golgi vesicles 1. It regulates pH homeostasis in Golgi secretory compartments 2 and is crucial for proper N-linked glycosylation of exported cargo proteins 1. The protein dynamically cycles between the trans-Golgi network, endosomes, and plasma membrane 3, with calcium-calmodulin regulating its transporter activity 3. Pathogenic variants in SLC9A7 cause X-linked intellectual developmental disorder. A recurrent missense variant (p.Leu515Phe) produces gain-of-function effects, alkalinizing the TGN/post-Golgi compartments and reducing N-glycosylation maturation with abnormal glycosylation profiles detected in patient sera 1. Splice site variants have been associated with intellectual disability, developmental delay, and seizures 4. However, benign variants exist with normal phenotypes in hemizygous males, indicating incomplete penetrance or variable pathogenicity depending on the specific mutation 5. Recent genome-wide association analysis identified SLC9A7 as a novel Alzheimer's disease locus 2, suggesting pH dysregulation in secretory compartments may contribute to amyloid-β accumulation and neurodegeneration.

Sources cited
1
SLC9A7 localization in trans-Golgi network and post-Golgi vesicles; role in N-linked glycosylation and TGN pH homeostasis; missense variant causes alkalinization and aberrant glycosylation
PMID: 30335141
2
SLC9A7 locus associated with Alzheimer's disease; regulates pH homeostasis in Golgi secretory compartments with effects on amyloid-β accumulation
PMID: 39250132
3
SLC9A7 functions as Na+/K+/H+ exchanger; cycles between TGN, endosomes, and plasma membrane; calcium-calmodulin regulates its activity
PMID: 18654930
4
SLC9A7 splice site variants (c.1030-1G>C) cause X-linked intellectual disability with developmental delay and seizures
PMID: 38818559
5
SLC9A7 c.1042-10G>C variant classified as benign; identified in phenotypically normal hemizygous males; does not affect RNA splicing
PMID: 41451488
6
SLC9A7 associated with X-linked mental retardation; identified with exonic STR expansions in conserved genomic regions
PMID: 36701310
Disease Associationsⓘ21
X-linked syndromic intellectual disabilityOpen Targets
0.46Moderate
intellectual developmental disorder, X-linked 108Open Targets
0.42Moderate
non-syndromic X-linked intellectual disabilityOpen Targets
0.37Weak
X-linked non-syndromic intellectual disabilityOpen Targets
0.37Weak
neoplasmOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
ulcerative colitisOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.01Suggestive
endometrial cancerOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
X-linked intellectual disabilityOpen Targets
0.01Suggestive
Intellectual disabilityOpen Targets
0.01Suggestive
Crohn's diseaseOpen Targets
0.01Suggestive
Invasive Breast CarcinomaOpen Targets
0.01Suggestive
lung adenocarcinomaOpen Targets
0.00Suggestive
colorectal carcinomaOpen Targets
0.00Suggestive
metastatic melanomaOpen Targets
0.00Suggestive
liver and intrahepatic bile duct neoplasmOpen Targets
0.00Suggestive
Intellectual developmental disorder, X-linked 108UniProt
Pathogenic Variants2
NM_001257291.2(SLC9A7):c.1543C>T (p.Leu515Phe)Likely pathogenic
not provided|SLC9A7-related neurodevelopmental disorder|Intellectual developmental disorder, X-linked 108
★★☆☆2020→ Residue 515
NM_001257291.2(SLC9A7):c.1147+2T>CLikely pathogenic
Intellectual developmental disorder, X-linked 108
★☆☆☆2025
View on ClinVar ↗
Related Genes
CHST7Protein interaction85%ZNF674Protein interaction84%SLC9A6Protein interaction83%SLC9A2Shared pathway82%SLC9A8Shared pathway82%SLC9A4Shared pathway82%
Tissue Expression6 tissues
Brain
100%
Ovary
49%
Bone Marrow
44%
Liver
42%
Heart
15%
Lung
13%
Gene Interaction Network
Click a node to explore
SLC9A7CHST7ZNF674SLC9A6SLC9A2SLC9A8SLC9A4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96T83
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.53Moderately Constrained
pLIⓘ
0.91Intolerant
Observed/Expected LoF0.36 [0.25–0.53]
RankingsWhere SLC9A7 stands among ~20K protein-coding genes
  • #13,310of 20,598
    Most Researched24
  • #4,540of 5,498
    Most Pathogenic Variants2
  • #3,323of 17,882
    Most Constrained (LOEUF)0.53 · top quartile
Genes detectedSLC9A7
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Role of the X Chromosome in Alzheimer Disease Genetics.
PMID: 39250132
JAMA Neurol · 2024
1.00
2
The Genomic landscape of short tandem repeats across multiple ancestries.
PMID: 36701310
PLoS One · 2023
0.90
3
[Pathogenicity analysis and genetic counseling for a hemizygous c.1042-10G>C variant of SLC9A7 gene].
PMID: 41451488
Zhonghua Yi Xue Yi Chuan Xue Za Zhi · 2025
0.80
4
[Clinical and genetic analysis of a child with X-linked mental retardation due to variant of SLC9A7 gene].
PMID: 38818559
Zhonghua Yi Xue Yi Chuan Xue Za Zhi · 2024
0.70
5
A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.
PMID: 30335141
Hum Mol Genet · 2019
0.60