SLC9C2

Summary

SLC9C2 (solute carrier family 9 member C2 (putative), HGNC:28664) is a protein-coding gene on chromosome 1q25.1, encoding Sodium/hydrogen exchanger 11 (Q5TAH2). Involved in pH regulation.

Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 284525 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 126 total
• MANE Select transcript: NM_178527

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28664
Approved symbol	SLC9C2
Name	solute carrier family 9 member C2 (putative)
Location	1q25.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC43026
Ensembl gene	ENSG00000162753
Ensembl biotype	protein_coding
OMIM	620338
Entrez	284525

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000367714, ENST00000466087, ENST00000476568, ENST00000479367, ENST00000648789

RefSeq mRNA: 1 — MANE Select: NM_178527 NM_178527

CCDS: CCDS1308

Canonical transcript exons

ENST00000367714 — 28 exons

Exon	Start	End
ENSE00001187729	173581847	173582008
ENSE00001337509	173583506	173583622
ENSE00001337513	173587665	173587830
ENSE00001337518	173600117	173600217
ENSE00001377657	173602751	173603072
ENSE00001445459	173601650	173601855
ENSE00001842936	173500460	173501097
ENSE00003479530	173523969	173524094
ENSE00003479637	173526663	173526714
ENSE00003500435	173534484	173534682
ENSE00003520628	173524779	173524927
ENSE00003541868	173557340	173557508
ENSE00003541982	173554733	173554814
ENSE00003556512	173506856	173507041
ENSE00003556909	173521301	173521399
ENSE00003557896	173533609	173533797
ENSE00003571238	173503266	173503326
ENSE00003594391	173509568	173509699
ENSE00003598652	173597904	173598032
ENSE00003599073	173548389	173548552
ENSE00003604749	173517537	173517704
ENSE00003605954	173505247	173505331
ENSE00003609825	173535830	173535949
ENSE00003620012	173529905	173530054
ENSE00003637805	173573182	173573325
ENSE00003681733	173536942	173537039
ENSE00003689871	173576661	173576760
ENSE00003692001	173547689	173547784

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 80.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1097 / max 28.8694, expressed in 32 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15949	0.1097	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	80.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.24	gold quality
right testis	UBERON:0004534	76.19	gold quality
left testis	UBERON:0004533	76.17	gold quality
testis	UBERON:0000473	74.41	gold quality
sperm	CL:0000019	72.60	silver quality
bronchial epithelial cell	CL:0002328	66.73	gold quality
bronchus	UBERON:0002185	65.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.80	gold quality
caudate nucleus	UBERON:0001873	60.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	59.93	silver quality
nucleus accumbens	UBERON:0001882	59.28	gold quality
fallopian tube	UBERON:0003889	56.92	gold quality
putamen	UBERON:0001874	54.48	gold quality
left adrenal gland cortex	UBERON:0035825	53.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.95	gold quality
left uterine tube	UBERON:0001303	53.67	gold quality
oviduct epithelium	UBERON:0004804	53.59	silver quality
left ovary	UBERON:0002119	53.00	gold quality
right adrenal gland cortex	UBERON:0035827	52.89	gold quality
adrenal cortex	UBERON:0001235	52.78	gold quality
lower lobe of lung	UBERON:0008949	52.78	silver quality
left adrenal gland	UBERON:0001234	52.28	gold quality
nasal cavity mucosa	UBERON:0001826	52.28	gold quality
right lung	UBERON:0002167	51.91	gold quality
amygdala	UBERON:0001876	51.69	gold quality
right adrenal gland	UBERON:0001233	51.64	gold quality
pituitary gland	UBERON:0000007	51.31	gold quality
adenohypophysis	UBERON:0002196	51.01	gold quality
right frontal lobe	UBERON:0002810	50.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting SLC9C2, 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-656-3P	100.00	72.15	2788
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-649	97.96	67.21	704
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-8055	97.62	66.09	1023

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	SLC9C2	ENSMUSG00000121369
rattus_norvegicus		ENSRNOG00000071269
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), SLC9C1 (ENSG00000172139), SLC9A4 (ENSG00000180251), SLC9A9 (ENSG00000181804), SLC9A8 (ENSG00000197818), SLC9A6 (ENSG00000198689)

Protein

Protein identifiers

Sodium/hydrogen exchanger 11 — Q5TAH2 (reviewed: Q5TAH2)

Alternative names: Na(+)/H(+) exchanger 11, Solute carrier family 9 member 11, Solute carrier family 9 member C2

All UniProt accessions (1): Q5TAH2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pH regulation.

Subcellular location. Membrane.

Domain organisation. Contains an ion transport-like region is related to the membrane segments of voltage-gated ion channels.

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

RefSeq proteins (1): NP_848622* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000595	cNMP-bd_dom	Domain
IPR006153	Cation/H_exchanger_TM	Domain
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR018422	Cation/H_exchanger_CPA1	Family
IPR018490	cNMP-bd_dom_sf	Homologous_superfamily
IPR027359	Volt_channel_dom_sf	Homologous_superfamily

Pfam: PF00027, PF00999

UniProt features (23 total): transmembrane region 15, sequence variant 3, glycosylation site 2, chain 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TAH2-F1	77.79	0.13

Functional residue map

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

Ligand- & substrate-binding residues (1): 867–999

Glycosylation sites (2): 447, 473

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-382551	Transport of small molecules
R-HSA-983712	Ion channel transport

MSigDB gene sets: 61 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, CMYB_01, GOBP_MONOATOMIC_CATION_TRANSPORT, WTGAAAT_UNKNOWN, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_REGULATION_OF_PH, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_IMPORT_INTO_CELL, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (8): regulation of intracellular pH (GO:0051453), potassium ion transmembrane transport (GO:0071805), sodium ion import across plasma membrane (GO:0098719), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), sodium ion transport (GO:0006814), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (3): sodium:proton antiporter activity (GO:0015385), potassium:proton antiporter activity (GO:0015386), antiporter activity (GO:0015297)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Ion channel transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	2
transport	2
metal cation:proton antiporter activity	2
regulation of pH	1
intracellular monoatomic cation homeostasis	1
regulation of biological quality	1
potassium ion transport	1
sodium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
monoatomic ion transport	1
metal ion transport	1
cellular process	1
sodium ion transmembrane transporter activity	1
solute:potassium antiporter activity	1
secondary active transmembrane transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC9C2	SLC9B2	Q86UD5	657
SLC9C2	SLC9B1	Q4ZJI4	634
SLC9C2	HLA-C	P04222	634
SLC9C2	TEX50	A0A1B0GTY4	561
SLC9C2	SLC9A6	Q92581	506
SLC9C2	SLC9A1	P19634	496
SLC9C2	SLC9A9	Q8IVB4	493
SLC9C2	SLC35G4	P0C7Q5	448
SLC9C2	ANKRD45	Q5TZF3	432
SLC9C2	ZBTB37	Q5TC79	431
SLC9C2	SLC7A13	Q8TCU3	420
SLC9C2	SLC9A5	Q14940	401
SLC9C2	CARD19	Q96LW7	401
SLC9C2	SLC35G3	Q8N808	399
SLC9C2	KIAA0040	Q15053	382

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SLC9C2	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): ACAA2 (Affinity Capture-MS), AMFR (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), CLPTM1 (Affinity Capture-MS), CYP51A1 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), DNAJB14 (Affinity Capture-MS), DNAJB4 (Affinity Capture-MS), DNAJC16 (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS), DNAJC7 (Affinity Capture-MS), EMC1 (Affinity Capture-MS), FAF2 (Affinity Capture-MS)

ESM2 similar proteins: A0A494BZU4, A0A7H0DND7, A0JNG0, A2T345, A4IIV4, C4QM85, E7F594, G5EDX4, O02051, O45306, P0DP42, P0DST5, P0DST6, P21061, P24763, P34362, P34363, P53053, Q09282, Q0II41, Q10907, Q11071, Q11085, Q13571, Q20249, Q297K8, Q2KHT4, Q2KJA5, Q32KQ5, Q5DC12, Q5GH77, Q5PQM0, Q5RD28, Q5REZ0, Q5TAH2, Q61168, Q6AXT9, Q6GV27, Q6GV28, Q7K1V5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	15
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3779 predictions. Top by Δscore:

Variant	Effect	Δscore
1:173509562:ACTT:A	donor_loss	1.0000
1:173509563:CTT:C	donor_loss	1.0000
1:173509564:TTA:T	donor_loss	1.0000
1:173509565:TACCT:T	donor_loss	1.0000
1:173509566:A:AG	donor_loss	1.0000
1:173509567:CCT:C	donor_gain	1.0000
1:173521291:AGTC:A	donor_gain	1.0000
1:173521299:A:AC	donor_gain	1.0000
1:173521300:C:CC	donor_gain	1.0000
1:173521310:T:TA	donor_gain	1.0000
1:173524774:ATTAC:A	donor_loss	1.0000
1:173524775:TTAC:T	donor_loss	1.0000
1:173524776:TA:T	donor_loss	1.0000
1:173524777:ACCT:A	donor_loss	1.0000
1:173524778:C:A	donor_loss	1.0000
1:173524798:T:TA	donor_gain	1.0000
1:173524807:T:C	donor_gain	1.0000
1:173524923:GAGTA:G	acceptor_gain	1.0000
1:173524924:AGTA:A	acceptor_gain	1.0000
1:173524925:GTA:G	acceptor_gain	1.0000
1:173524926:TA:T	acceptor_gain	1.0000
1:173524927:AC:A	acceptor_loss	1.0000
1:173524928:C:CC	acceptor_gain	1.0000
1:173524929:T:C	acceptor_loss	1.0000
1:173524932:A:T	acceptor_gain	1.0000
1:173524934:C:CT	acceptor_gain	1.0000
1:173524935:A:T	acceptor_gain	1.0000
1:173526658:CCTA:C	donor_loss	1.0000
1:173526659:CTA:C	donor_loss	1.0000
1:173526660:TACCT:T	donor_loss	1.0000

AlphaMissense

7465 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:173524007:A:G	W868R	0.995
1:173524007:A:T	W868R	0.995
1:173509627:A:G	W994R	0.992
1:173509627:A:T	W994R	0.992
1:173509614:G:T	A998D	0.986
1:173505300:A:G	L1086P	0.985
1:173509615:C:G	A998P	0.984
1:173517552:A:C	C964W	0.983
1:173529962:A:C	S752R	0.983
1:173529962:A:T	S752R	0.983
1:173529964:T:G	S752R	0.983
1:173587720:G:C	S156R	0.982
1:173587720:G:T	S156R	0.982
1:173587722:T:G	S156R	0.982
1:173521333:C:G	G903R	0.980
1:173521333:C:T	G903R	0.980
1:173517590:A:G	C952R	0.978
1:173587807:G:C	S127R	0.978
1:173587807:G:T	S127R	0.978
1:173587809:T:G	S127R	0.978
1:173509666:C:G	G981R	0.977
1:173517586:A:G	L953P	0.975
1:173548430:A:G	W474R	0.975
1:173548430:A:T	W474R	0.975
1:173581965:G:C	S228R	0.975
1:173581965:G:T	S228R	0.975
1:173581967:T:G	S228R	0.975
1:173505308:G:C	S1083R	0.974
1:173505308:G:T	S1083R	0.974
1:173505310:T:G	S1083R	0.974

dbSNP variants (sampled 300 via entrez): RS1000061607 (1:173532999 G>A,C), RS1000090813 (1:173540035 G>T), RS1000120936 (1:173526268 A>G), RS1000124521 (1:173572057 A>C,G), RS1000161307 (1:173525851 C>G), RS1000215680 (1:173522375 A>G), RS1000229822 (1:173536386 G>A), RS1000276001 (1:173589371 AAG>A), RS1000281196 (1:173568374 A>T), RS1000328479 (1:173592402 A>C), RS1000330433 (1:173519949 C>G,T), RS1000357842 (1:173502100 T>C), RS1000381649 (1:173529815 G>A,C), RS1000387817 (1:173572330 G>A), RS1000391773 (1:173575140 T>A)

Disease associations

OMIM: gene MIM:620338 | disease phenotypes: MIM:601859

GenCC curated gene-disease

Mondo (1): autoimmune lymphoproliferative syndrome type 1 (MONDO:0011158)

Orphanet (1): Autoimmune lymphoproliferative syndrome (Orphanet:3261)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	increases reaction, affects binding	1
Benzo(a)pyrene	affects methylation	1
Oxygen	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT06730126	PHASE2	RECRUITING	Study of the ITK Inhibitor Soquelitinib to Reduce Lymphoproliferation and Improve Cytopenias in Autoimmune Lymphoproliferative Syndrome (ALPS)-FAS Patients
NCT00392951	PHASE1/PHASE2	COMPLETED	Sirolimus for Autoimmune Disease of Blood Cells
NCT00605657	PHASE1/PHASE2	COMPLETED	Valproic Acid (Depakote[Registered Trademark]) to Treat Autoimmune Lymphoproliferative Syndrome (ALPS)
NCT01672918	Not specified	WITHDRAWN	Fluorodeoxyglucose Imaging Studies to Detect Lymphoma
NCT04902807	Not specified	RECRUITING	Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation