SLC9A9

Summary

SLC9A9 (solute carrier family 9 member A9, HGNC:20653) is a protein-coding gene on chromosome 3q24, encoding Sodium/hydrogen exchanger 9 (Q8IVB4). Endosomal Na(+), K(+)/H(+) antiporter.

This gene encodes a sodium/proton exchanger that is a member of the solute carrier 9 protein family. The encoded protein localizes the to the late recycling endosomes and may play an important role in maintaining cation homeostasis. Mutations in this gene are associated with autism susceptibility 16 and attention-deficit/hyperactivity disorder.

Source: NCBI Gene 285195 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism, susceptibility to, 16 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 22
• Clinical variants (ClinVar): 147 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_173653

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20653
Approved symbol	SLC9A9
Name	solute carrier family 9 member A9
Location	3q24
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35613, NHE9
Ensembl gene	ENSG00000181804
Ensembl biotype	protein_coding
OMIM	608396
Entrez	285195

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000316549, ENST00000474151, ENST00000474727, ENST00000483124, ENST00000498717, ENST00000900956

RefSeq mRNA: 1 — MANE Select: NM_173653 NM_173653

CCDS: CCDS33872

Canonical transcript exons

ENST00000316549 — 16 exons

Exon	Start	End
ENSE00001216854	143832019	143832221
ENSE00001216870	143265222	143266929
ENSE00001852533	143848148	143848468
ENSE00002230373	143268875	143268980
ENSE00002244034	143552362	143552450
ENSE00002265455	143493653	143493764
ENSE00002269487	143363484	143363563
ENSE00002305051	143382060	143382114
ENSE00002310776	143495335	143495448
ENSE00002321256	143467037	143467190
ENSE00003492867	143578585	143578723
ENSE00003580825	143574088	143574193
ENSE00003608004	143795001	143795077
ENSE00003622764	143693192	143693307
ENSE00003646808	143796826	143796903
ENSE00003680468	143652255	143652360

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 97.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3592 / max 284.0476, expressed in 1332 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44878	13.3592	1332

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.41	gold quality
tendon	UBERON:0000043	92.15	gold quality
monocyte	CL:0000576	88.75	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.73	gold quality
leukocyte	CL:0000738	88.42	gold quality
spinal cord	UBERON:0002240	88.10	gold quality
tendon of biceps brachii	UBERON:0008188	87.14	gold quality
corpus callosum	UBERON:0002336	86.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.70	silver quality
left ventricle myocardium	UBERON:0006566	85.74	silver quality
lymph node	UBERON:0000029	85.26	gold quality
upper arm skin	UBERON:0004263	84.95	silver quality
layer of synovial tissue	UBERON:0007616	84.67	gold quality
granulocyte	CL:0000094	83.75	gold quality
esophagus squamous epithelium	UBERON:0006920	83.24	gold quality
ileal mucosa	UBERON:0000331	83.17	gold quality
esophagus mucosa	UBERON:0002469	83.09	gold quality
urinary bladder	UBERON:0001255	82.90	gold quality
superficial temporal artery	UBERON:0001614	82.77	gold quality
substantia nigra	UBERON:0002038	82.66	gold quality
gall bladder	UBERON:0002110	82.63	gold quality
right coronary artery	UBERON:0001625	82.53	gold quality
synovial joint	UBERON:0002217	82.44	gold quality
colonic epithelium	UBERON:0000397	81.91	gold quality
spleen	UBERON:0002106	81.79	gold quality
esophagus	UBERON:0001043	81.64	gold quality
midbrain	UBERON:0001891	81.58	gold quality
pancreatic ductal cell	CL:0002079	81.44	silver quality
vagina	UBERON:0000996	81.26	gold quality
smooth muscle tissue	UBERON:0001135	81.14	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	1152.44
E-HCAD-35	yes	31.29
E-ANND-3	yes	11.41
E-MTAB-6678	yes	11.06
E-CURD-119	yes	6.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting SLC9A9, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548P	99.98	72.25	3784
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-202-3P	99.84	71.41	1290

Literature-anchored findings (GeneRIF, showing 18)

• results suggest that SLC9A9 may be related to hyperactive-impulsive symptoms in AD/HD and the disruption of SLC9A9 may be responsible for the behavioral phenotype observed in the inversion family (PMID:20032819)
• This review defines NHE6-9 as organellar NHEs that are fairly dynamic, implying that they are subjected to intracellular trafficking and thus they continuously shuttle between organelles and the plasma membrane. (PMID:21171650)
• SLC9A9 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• 33 directly measured and 13 derived glycosylation traits in 3533 individuals were identified and three novel gene association (MGAT5, B3GAT1 and SLC9A9) were identified using an additional European cohort. (PMID:21908519)
• find interesting gene expression changes in endosomal NHE6 and NHE9 in postmortem autism brains. (PMID:23508127)
• Loss-of-function mutations in NHE9 may contribute to autistic phenotype by modulating synaptic membrane protein expression and neurotransmitter clearance. (PMID:24065030)
• the expression of SLC9A9 can be a prognostic predictor for ESCC. (PMID:25835977)
• SLC9A9 appears to influence the differentiation of T cells to a proinflammatory fate and may have a broader role in multiple sclerosis disease activity. There is an association between rs9828519(G) and nonresponse to IFNbeta treatment. (PMID:25914168)
• Taken together, our findings demonstrate that NHE9 can be an effective predictor of chemoradiotherapy response in esophageal squamous cell carcinoma (PMID:25915159)
• SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. (PMID:27439572)
• rs9828519 polymorphism is associated with differential expression of SLC9A9 in occipital cortex, intralobular white matter, and substantia nigra in patients with multiple sclerosis. (PMID:27766536)
• Ectopic expression of NHE9 in human brain microvascular endothelial cells without external cues induced up-regulation of the transferrin receptor (TfR) and down-regulation of ferritin, leading to an increase in iron uptake (PMID:28130443)
• SLC9A9 has an oncogenic function by being related to EGFR signaling, suggesting SLC9A9 may be a novel prognostic indicator and a therapeutic target in colorectal cancer (PMID:28476790)
• downregulation of miR-135a as a potential mechanism underlying the high NHE9 expression observed in subset of glioblastomas (PMID:29268774)
• results provide a detailed understanding of the functions of protein NHE9 and its disrupted interactions, possibly underlying Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorders. (PMID:30927234)
• Sodium hydrogen exchanger 9 NHE9 (SLC9A9) and its emerging roles in neuropsychiatric comorbidity. (PMID:32400953)
• Structure and elevator mechanism of the mammalian sodium/proton exchanger NHE9. (PMID:33118634)
• Genes for endosomal pH regulators NHE6 and NHE9 are dysregulated in the substantia nigra in Parkinson’s disease. (PMID:38945311)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc9a9	ENSMUSG00000031129
rattus_norvegicus	Slc9a9	ENSRNOG00000008554
drosophila_melanogaster	Nhe3	FBGN0028703
drosophila_melanogaster	Nhe2	FBGN0040297
caenorhabditis_elegans		WBGENE00003730
caenorhabditis_elegans		WBGENE00003732
caenorhabditis_elegans		WBGENE00003733
caenorhabditis_elegans		WBGENE00003734

Paralogs (10): SLC9A7 (ENSG00000065923), SLC9A3 (ENSG00000066230), SLC9A1 (ENSG00000090020), SLC9A2 (ENSG00000115616), SLC9A5 (ENSG00000135740), SLC9C2 (ENSG00000162753), SLC9C1 (ENSG00000172139), SLC9A4 (ENSG00000180251), SLC9A8 (ENSG00000197818), SLC9A6 (ENSG00000198689)

Protein

Protein identifiers

Sodium/hydrogen exchanger 9 — Q8IVB4 (reviewed: Q8IVB4)

Alternative names: Na(+)/H(+) exchanger 9, Solute carrier family 9 member 9

All UniProt accessions (3): C9IZP1, Q8IVB4, F8WF83

UniProt curated annotations — full annotation on UniProt →

Function. Endosomal Na(+), K(+)/H(+) antiporter. Mediates the electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) or K(+). By facilitating proton efflux, SLC9A9 counteracts the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal acidification. Regulates organellar pH and consequently, e.g., endosome maturation and endocytic trafficking of plasma membrane receptors and neurotransporters. Promotes the recycling of transferrin receptors back to the cell surface to facilitate additional iron uptake in the brain. Regulates synaptic transmission by regulating the luminal pH of axonal endosomes. Regulates phagosome lumenal pH, thus affecting phagosome maturation, and consequently, microbicidal activity in macrophages. Can also be active at the cell surface of specialized cells, e.g., in the inner ear hair bundles uses the high K(+) of the endolymph to regulate intracellular pH.

Subunit / interactions. Homodimer; phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) could be involved in the dimer stabilization. Interacts (via the C-terminus) with RACK1. Interacts with CHP1.

Subcellular location. Late endosome membrane. Early endosome membrane. Recycling endosome membrane. Cell membrane. Cytoplasmic vesicle. Phagosome membrane.

Tissue specificity. Ubiquitously expressed in all tissues tested. Expressed at highest levels in heart and skeletal muscle, followed by placenta, kidney, and liver. Expressed in the brain, in the medulla and spinal cord.

Disease relevance. A chromosomal aberration involving SLC9A9 has been found in a family with early-onset behavioral/developmental disorder with features of attention deficit-hyperactivity disorder and intellectual disability. Inversion inv(3)(p14:q21). The inversion disrupts DOCK3 and SLC9A9. 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 intellectual disability. AUTS16 can be associated with epilepsy. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. Conditioned medium from iron-depleted astrocytes increases SLC9A9 levels in human blood-brain barrier endothelial cells (hBMVECs).

Similarity. Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.

RefSeq proteins (1): NP_775924* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002090	NHE-6/7/9	Family
IPR004709	NaH_exchanger	Family
IPR006153	Cation/H_exchanger_TM	Domain
IPR018422	Cation/H_exchanger_CPA1	Family

Pfam: PF00999

Catalyzed reactions (Rhea), 2 shown:

• Na(+)(in) + H(+)(out) = Na(+)(out) + H(+)(in) (RHEA:29419)
• K(+)(in) + H(+)(out) = K(+)(out) + H(+)(in) (RHEA:29467)

UniProt features (35 total): topological domain 13, transmembrane region 13, sequence variant 3, mutagenesis site 3, chain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVB4-F1	73.46	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 96

Mutagenesis-validated functional residues (3):

Position	Phenotype
176	normal protein expression. does not affect endosomal localization. fails to alkalinize endosomal lumen.
236	normal protein expression. fails to alkalinize endosomal lumen. does not affect endosomal localization.
438	normal protein expression. fails to alkalinize endosomal lumen. does not affect endosomal localization.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-425986	Sodium/Proton exchangers
R-HSA-5619052	Defective SLC9A9 causes autism 16 (AUTS16)
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 242 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, RRAGTTGT_UNKNOWN, chr3q24, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GCANCTGNY_MYOD_Q6, ATACCTC_MIR202, AAGCCAT_MIR135A_MIR135B, GOBP_MONOATOMIC_CATION_TRANSPORT, GTGCCTT_MIR506, GOBP_PHAGOSOME_MATURATION, TGCTGAY_UNKNOWN, ATGCTGG_MIR338, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_REGULATION_OF_PH, RYTTCCTG_ETS2_B

GO Biological Process (12): monoatomic ion transport (GO:0006811), defense response to bacterium (GO:0042742), regulation of intracellular pH (GO:0051453), potassium ion transmembrane transport (GO:0071805), phagosome maturation (GO:0090382), sodium ion import across plasma membrane (GO:0098719), monoatomic cation transport (GO:0006812), sodium ion transport (GO:0006814), regulation of pH (GO:0006885), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (4): sodium:proton antiporter activity (GO:0015385), potassium:proton antiporter activity (GO:0015386), protein binding (GO:0005515), antiporter activity (GO:0015297)

GO Cellular Component (11): early endosome (GO:0005769), plasma membrane (GO:0005886), phagocytic vesicle membrane (GO:0030670), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), early phagosome (GO:0032009), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Metal ion SLC transporters	1
SLC transporter disorders	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	3
endosome membrane	3
transport	2
metal cation:proton antiporter activity	2
endosome	2
phagocytic vesicle	2
defense response	1
response to bacterium	1
regulation of pH	1
intracellular monoatomic cation homeostasis	1
regulation of biological quality	1
potassium ion transport	1
phagolysosome assembly	1
exocytosis	1
organelle organization	1
sodium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
monoatomic ion transport	1
metal ion transport	1
monoatomic cation homeostasis	1
biological regulation	1
sodium ion transport	1
cellular process	1
sodium ion transmembrane transporter activity	1
solute:potassium antiporter activity	1
binding	1
secondary active transmembrane transporter activity	1
membrane	1
cell periphery	1
endocytic vesicle membrane	1
early endosome	1
late endosome	1
recycling endosome	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC9A9	DOCK3	Q8IZD9	889
SLC9A9	RACK1	P25388	854
SLC9A9	DIPK2A	Q8NDZ4	853
SLC9A9	SLC9B2	Q86UD5	783
SLC9A9	NPAS4	Q8IUM7	738
SLC9A9	NLGN4X	Q8N0W4	680
SLC9A9	NLGN3	Q9NZ94	677
SLC9A9	SHANK2	Q9UPX8	672
SLC9A9	PTCHD1	Q96NR3	668
SLC9A9	CNTNAP2	Q9UHC6	642
SLC9A9	SLC9B1	Q4ZJI4	603
SLC9A9	SLC6A3	Q01959	553
SLC9A9	KIAA0319	Q5VV43	548
SLC9A9	SLC9C1	Q4G0N8	543
SLC9A9	AUTS2	Q8WXX7	526

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SLC9A9	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.510
SLC9A9	OPRM1	psi-mi:“MI:0915”(physical association)	0.370
SLC9A9	TP53	psi-mi:“MI:0915”(physical association)	0.370
SLC9A9	PODXL	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): SLC9A9 (Two-hybrid), SLC9A9 (Affinity Capture-Western), SLC9A9 (Two-hybrid), SLC9A9 (Two-hybrid), SLC9A9 (Affinity Capture-MS), PTMA (Affinity Capture-MS), GNB1 (Affinity Capture-MS), ATP5G1 (Affinity Capture-MS), RAB5C (Affinity Capture-MS), ARF6 (Affinity Capture-MS), NDUFA6 (Affinity Capture-MS), PDCD6 (Affinity Capture-MS), UQCR10 (Affinity Capture-MS), ARL1 (Affinity Capture-MS), PLOD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A075B734, A1L272, A2IBY8, A8W649, A9Y006, D4A7H1, E7EXX2, F7B113, O14520, O35454, O54794, O62735, O94956, P34080, P35525, P41181, P47862, P47863, P47864, P51789, P51797, P56402, P56403, P79099, Q06495, Q06496, Q08DE6, Q4R691, Q5PQL3, Q62052, Q866S3, Q8BLV3, Q8BXB6, Q8BZ00, Q8IVB4, Q8K078, Q8MIQ9, Q8R2N1, Q8TCT8, Q921R8

Diamond homologs: A1L3P4, B2RXE2, D3ZJ86, D4A7H1, F7B113, G3X939, M5A7P9, O13726, P19634, P23791, P26431, P26432, P26433, P26434, P48761, P48762, P48763, P48764, Q01345, Q04121, Q14940, Q28362, Q3ZAS0, Q4L208, Q4R8V4, Q552S0, Q56XP4, Q58916, Q5ZJ75, Q61165, Q68KI4, Q6AI14, Q84WG1, Q8BLV3, Q8BUE1, Q8BZ00, Q8IVB4, Q8R4D1, Q8RWU6, Q8S396

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SLC9A9	“down-regulates quantity”	hydron	relocalization
SLC9A9	“up-regulates quantity”	sodium(1+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

147 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	94
Likely benign	19
Benign	14

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
998156	NM_173653.4(SLC9A9):c.587del (p.Asn196fs)	Pathogenic
4074730	NM_173653.4(SLC9A9):c.1774C>T (p.Gln592Ter)	Likely pathogenic

SpliceAI

3986 predictions. Top by Δscore:

Variant	Effect	Δscore
3:143266929:CCTGG:C	acceptor_loss	1.0000
3:143266931:T:C	acceptor_loss	1.0000
3:143363560:CTTC:C	acceptor_gain	1.0000
3:143363561:TTCC:T	acceptor_loss	1.0000
3:143363562:TCCT:T	acceptor_loss	1.0000
3:143363563:CCTGG:C	acceptor_loss	1.0000
3:143363564:C:CC	acceptor_gain	1.0000
3:143363565:T:A	acceptor_loss	1.0000
3:143467032:CTCA:C	donor_loss	1.0000
3:143467033:TCA:T	donor_loss	1.0000
3:143467034:CA:C	donor_loss	1.0000
3:143467035:A:AT	donor_loss	1.0000
3:143467036:C:T	donor_loss	1.0000
3:143467190:CCT:C	acceptor_gain	1.0000
3:143467192:T:C	acceptor_gain	1.0000
3:143467192:T:TC	acceptor_gain	1.0000
3:143552356:TTTTA:T	donor_loss	1.0000
3:143552357:TTTA:T	donor_loss	1.0000
3:143552358:TTA:T	donor_loss	1.0000
3:143552359:TA:T	donor_loss	1.0000
3:143552361:C:A	donor_loss	1.0000
3:143552446:TATCC:T	acceptor_gain	1.0000
3:143552448:TCC:T	acceptor_gain	1.0000
3:143552449:CCC:C	acceptor_gain	1.0000
3:143552451:C:CC	acceptor_gain	1.0000
3:143578609:AGACC:A	donor_gain	1.0000
3:143578719:TAGAA:T	acceptor_gain	1.0000
3:143652246:GGTAC:G	donor_loss	1.0000
3:143652247:GTAC:G	donor_loss	1.0000
3:143652248:TACTT:T	donor_loss	1.0000

AlphaMissense

4247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:143467181:C:T	G442E	0.999
3:143467182:C:G	G442R	0.999
3:143467182:C:T	G442R	0.999
3:143495397:C:G	G381R	0.999
3:143495407:G:C	F377L	0.999
3:143495407:G:T	F377L	0.999
3:143495409:A:G	F377L	0.999
3:143574116:G:C	F324L	0.999
3:143574116:G:T	F324L	0.999
3:143574118:A:G	F324L	0.999
3:143574122:A:C	S322R	0.999
3:143574122:A:T	S322R	0.999
3:143574124:T:G	S322R	0.999
3:143574127:A:G	W321R	0.999
3:143574127:A:T	W321R	0.999
3:143652261:A:G	L250P	0.999
3:143652279:T:A	D244V	0.999
3:143652279:T:G	D244A	0.999
3:143652281:A:C	N243K	0.999
3:143652281:A:T	N243K	0.999
3:143652282:T:A	N243I	0.999
3:143652290:A:C	S240R	0.999
3:143652290:A:T	S240R	0.999
3:143652292:T:G	S240R	0.999
3:143693197:T:C	D215G	0.999
3:143693218:C:T	G208D	0.999
3:143796854:A:T	I143K	0.999
3:143796866:A:G	L139P	0.999
3:143796866:A:T	L139Q	0.999
3:143832209:C:T	G63E	0.999

dbSNP variants (sampled 300 via entrez): RS1000004032 (3:143647893 C>T), RS1000005977 (3:143503175 G>A), RS1000006363 (3:143337364 C>T), RS1000010013 (3:143544555 A>G), RS1000022116 (3:143451426 A>T), RS1000022787 (3:143481561 G>A), RS1000024376 (3:143396942 T>G), RS1000038567 (3:143666044 T>C), RS1000039387 (3:143603418 A>G), RS1000039609 (3:143560960 C>A), RS1000041216 (3:143342856 G>A,C), RS1000046556 (3:143415289 A>G), RS1000049120 (3:143268443 TC>T), RS1000054356 (3:143631347 T>C), RS1000060504 (3:143386055 G>A)

Disease associations

OMIM: gene MIM:608396 | disease phenotypes: MIM:613410, MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
autism, susceptibility to, 16	Limited	Autosomal dominant
autism spectrum disorder	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autism spectrum disorder	Disputed	AD

Mondo (3): autism, susceptibility to, 16 (MONDO:0013258), colorectal cancer (MONDO:0005575), autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000107_13	Tonometry	4.000000e-06
GCST000684_4	Attention deficit hyperactivity disorder	6.000000e-06
GCST000765_4	Non-alcoholic fatty liver disease histology (other)	3.000000e-06
GCST001520_11	Response to angiotensin II receptor blocker therapy	3.000000e-06
GCST001835_1	Response to cholinesterase inhibitors in Alzheimer’s disease	2.000000e-06
GCST003444_1	Response to carboplatin and paclitaxel in ovarian cancer (MTT IC50)	6.000000e-07
GCST003542_32	Night sleep phenotypes	7.000000e-07
GCST003632_6	Survival in sporadic amyotrophic lateral sclerosis	6.000000e-07
GCST003854_3	Gut microbiota (functional units)	3.000000e-08
GCST005046_22	N-glycan levels	4.000000e-13
GCST005046_41	N-glycan levels	3.000000e-08
GCST005364_2	Opioid requirements during laparoscopic-assisted colectomy	4.000000e-06
GCST005569_34	Rheumatoid arthritis	2.000000e-06
GCST006446_7	Ulna and radius bone mineral density	9.000000e-06
GCST008156_61	Hip circumference adjusted for BMI	4.000000e-06
GCST008758_41	Pre-treatment viral load in HIV-1 infection	7.000000e-17
GCST008892_4	Working memory	3.000000e-06
GCST009391_334	Metabolite levels	9.000000e-06
GCST010252_1	Systolic blood pressure x quantitative lifestyle risk score interaction (2df test)	2.000000e-07
GCST010253_3	Systolic blood pressure x quantitative lifestyle risk score interaction (1df test)	2.000000e-06
GCST012248_1	IgG N-glycosylation phenotypes (multivariate analysis)	9.000000e-11
GCST90002395_392	Mean platelet volume	5.000000e-11

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0005195	response to cholinesterase inhibitor
EFO:0006952	cytotoxicity measurement
EFO:0000714	survival time
EFO:0007874	gut microbiome measurement
EFO:0004999	N-glycan measurement
EFO:0008541	response to opioid
EFO:0008544	analgesia requirement measurement
EFO:0007933	radius bone mineral density
EFO:0008039	BMI-adjusted hip circumference
EFO:0010125	viral load
EFO:0004335	short-term memory
EFO:0010432	triacylglycerol 56:5 measurement
EFO:0006335	systolic blood pressure
EFO:0010724	lifestyle measurement
EFO:0005193	serum IgG glycosylation measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4839603	SLC9A9		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC9 family of sodium/hydrogen exchangers

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, affects expression	3
bisphenol A	decreases methylation, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
Aflatoxin B1	increases methylation, decreases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	decreases expression	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
3-iodothyronamine	affects uptake	1
abrine	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Carbamazepine	affects expression	1
Demecolcine	increases expression	1
Dexamethasone	increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vincristine	increases expression	1
Cyclosporine	increases expression	1
Medroxyprogesterone Acetate	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4FI	1321N1-SLC9A9-KO-c10	Cancer cell line	Male
CVCL_D4FJ	1321N1-SLC9A9-KO-c6	Cancer cell line	Male
CVCL_E0P7	Ubigene HeLa SLC9A9 KO	Cancer cell line	Female
CVCL_TP31	HAP1 SLC9A9 (-) 1	Cancer cell line	Male
CVCL_TP32	HAP1 SLC9A9 (-) 2	Cancer cell line	Male
CVCL_TP33	HAP1 SLC9A9 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

600 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)