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SLC4A9

gene
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Also known as AE4

Summary

SLC4A9 (solute carrier family 4 member 9, HGNC:11035) is a protein-coding gene on chromosome 5q31.3, encoding Anion exchange protein 4 (Q96Q91). Electroneutral Cl(-)/HCO3(-) antiporter that favors chloride ion entry and efflux of hydrogencarbonate and sodium ion across the basolateral membrane and may participate in salivary secretion.

The protein encoded by this gene is a membrane protein involved in anion exchange. Expression of this gene is mostly limited to the kidney. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 83697 — RefSeq curated summary.

At a glance

  • GWAS associations: 2
  • Clinical variants (ClinVar): 118 total
  • MANE Select transcript: NM_031467

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11035
Approved symbolSLC4A9
Namesolute carrier family 4 member 9
Location5q31.3
Locus typegene with protein product
StatusApproved
AliasesAE4
Ensembl geneENSG00000113073
Ensembl biotypeprotein_coding
OMIM610207
Entrez83697

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 2 retained_intron

ENST00000432095, ENST00000504742, ENST00000506545, ENST00000506757, ENST00000507527, ENST00000514849, ENST00000890329, ENST00000890330, ENST00000890331, ENST00000890332, ENST00000890333, ENST00000890334, ENST00000890335, ENST00000890336, ENST00000890337, ENST00000890338, ENST00000890339, ENST00000890340, ENST00000890341, ENST00000890342, ENST00000890343

RefSeq mRNA: 4 — MANE Select: NM_031467 NM_001258426, NM_001258427, NM_001258428, NM_031467

CCDS: CCDS47278, CCDS58973, CCDS58974, CCDS58975

Canonical transcript exons

ENST00000506757 — 22 exons

ExonStartEnd
ENSE00000764840140364054140364187
ENSE00000814143140362017140362174
ENSE00000814144140362445140362532
ENSE00000814145140362912140363066
ENSE00000814146140363439140363555
ENSE00000814147140363728140363902
ENSE00000814148140364363140364625
ENSE00000898567140365520140365578
ENSE00000898568140365834140366022
ENSE00000898570140367420140367581
ENSE00000898571140367720140367898
ENSE00000898572140368587140368659
ENSE00000898574140371451140371624
ENSE00000898575140372242140372397
ENSE00000973562140361254140361367
ENSE00000973563140361808140361863
ENSE00001194235140360194140360466
ENSE00001685273140360812140360972
ENSE00002042897140374827140375141
ENSE00002496956140371095140371163
ENSE00003496279140366151140366264
ENSE00003656687140372745140372843

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 88.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0300 / max 21.0793, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
588970.03006

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
adult mammalian kidneyUBERON:000008288.09gold quality
kidney epitheliumUBERON:000481985.29gold quality
metanephros cortexUBERON:001053384.91gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047384.10gold quality
kidneyUBERON:000211381.82gold quality
cardiac muscle of right atriumUBERON:000337979.90gold quality
left ventricle myocardiumUBERON:000656679.67gold quality
renal medullaUBERON:000036278.40gold quality
metanephrosUBERON:000008177.93gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451177.86gold quality
upper arm skinUBERON:000426376.69gold quality
tendon of biceps brachiiUBERON:000818876.23silver quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099175.56gold quality
cortex of kidneyUBERON:000122575.52gold quality
vena cavaUBERON:000408775.00silver quality
nasal cavity epitheliumUBERON:000538474.22gold quality
buccal mucosa cellCL:000233673.26gold quality
spermCL:000001972.86silver quality
skeletal muscle tissue of biceps brachiiUBERON:000450267.69gold quality
parotid glandUBERON:000183167.62gold quality
body of tongueUBERON:001187667.21gold quality
cerebellar vermisUBERON:000472066.84silver quality
vastus lateralisUBERON:000137966.59gold quality
lower lobe of lungUBERON:000894966.59silver quality
gingivaUBERON:000182866.51gold quality
heart right ventricleUBERON:000208066.40gold quality
quadriceps femorisUBERON:000137766.23gold quality
tracheaUBERON:000312666.14silver quality
tongueUBERON:000172366.13gold quality
ponsUBERON:000098866.09silver quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

ExperimentMarker?Max mean expression
E-GEOD-131882yes4424.20
E-CURD-119yes4010.46
E-ANND-3yes3.59
E-CURD-135no2075.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXI1

miRNA regulators (miRDB)

17 targeting SLC4A9, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4753-3P99.9071.033786
HSA-MIR-130B-5P99.8368.501888
HSA-MIR-129999.7771.242389
HSA-MIR-5004-5P99.6866.631294
HSA-MIR-4743-3P99.6268.122095
HSA-MIR-568399.3668.592083
HSA-MIR-130A-5P99.3370.262623
HSA-MIR-6734-3P99.1566.271627
HSA-MIR-1227-5P98.6565.321549
HSA-MIR-1245B-3P98.0168.911387
HSA-MIR-4778-5P97.9668.061634
HSA-MIR-1226-3P97.5166.321063
HSA-MIR-6869-5P97.1767.06634
HSA-MIR-6851-3P95.7365.11688
HSA-MIR-5586-3P95.5167.00805
HSA-MIR-659-5P95.3665.00300
HSA-MIR-328-3P92.8264.37521

Cross-species orthologs

6 orthologs

OrganismSymbolGene ID
mus_musculusSlc4a9ENSMUSG00000024485
rattus_norvegicusSlc4a9ENSRNOG00000018525
drosophila_melanogasterAe2FBGN0036043
drosophila_melanogasterNdae1FBGN0259111
caenorhabditis_elegansabts-1WBGENE00009920
caenorhabditis_elegansWBGENE00019844

Paralogs (9): SLC4A1 (ENSG00000004939), SLC4A7 (ENSG00000033867), SLC4A8 (ENSG00000050438), SLC4A4 (ENSG00000080493), SLC4A11 (ENSG00000088836), SLC4A3 (ENSG00000114923), SLC4A10 (ENSG00000144290), SLC4A2 (ENSG00000164889), SLC4A5 (ENSG00000188687)

Protein

Protein identifiers

Anion exchange protein 4 — Q96Q91 (reviewed: Q96Q91)

Alternative names: Sodium bicarbonate cotransporter 5, Solute carrier family 4 member 9

All UniProt accessions (1): Q96Q91

UniProt curated annotations — full annotation on UniProt →

Function. Electroneutral Cl(-)/HCO3(-) antiporter that favors chloride ion entry and efflux of hydrogencarbonate and sodium ion across the basolateral membrane and may participate in salivary secretion. Also mediates Cl(-)/HCO3(-) exchange activity in the presence of K(+) as well as Cs(+), Li(+), and Rb(+). Does not contribute to Cl(-)/HCO3(-) exchanger in the apical membrane of the upper villous epithelium.

Subcellular location. Basolateral cell membrane.

Tissue specificity. Kidney specific.

Similarity. Belongs to the anion exchanger (TC 2.A.31) family.

Isoforms (4)

UniProt IDNamesCanonical?
Q96Q91-11yes
Q96Q91-22
Q96Q91-33
Q96Q91-44

RefSeq proteins (4): NP_001245355, NP_001245356, NP_001245357, NP_113655* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR003020HCO3_transpt_eukFamily
IPR003024Na/HCO3_transptFamily
IPR011531HCO3_transpt-like_TM_domDomain
IPR013769Band3_cytoplasmic_domDomain
IPR016152PTrfase/Anion_transptrHomologous_superfamily

Pfam: PF00955, PF07565

Catalyzed reactions (Rhea), 5 shown:

  • 2 hydrogencarbonate(out) + chloride(in) + Na(+)(out) = 2 hydrogencarbonate(in) + chloride(out) + Na(+)(in) (RHEA:72739)
  • K(+)(in) + 2 hydrogencarbonate(in) + chloride(out) = K(+)(out) + 2 hydrogencarbonate(out) + chloride(in) (RHEA:75059)
  • Li(+)(in) + 2 hydrogencarbonate(in) + chloride(out) = Li(+)(out) + 2 hydrogencarbonate(out) + chloride(in) (RHEA:75063)
  • Rb(+)(in) + 2 hydrogencarbonate(in) + chloride(out) = Rb(+)(out) + 2 hydrogencarbonate(out) + chloride(in) (RHEA:75067)
  • Cs(+)(in) + 2 hydrogencarbonate(in) + chloride(out) = Cs(+)(out) + 2 hydrogencarbonate(out) + chloride(in) (RHEA:75071)

UniProt features (30 total): transmembrane region 11, region of interest 5, glycosylation site 4, splice variant 4, sequence conflict 4, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96Q91-F172.500.26

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 (4): 183, 576, 600, 979

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

IDPathway
R-HSA-425381Bicarbonate transporters
R-HSA-382551Transport of small molecules
R-HSA-425393
R-HSA-425407SLC-mediated transmembrane transport

MSigDB gene sets: 86 (showing top): GOBP_DIGESTION, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_BICARBONATE_TRANSPORT, GOBP_SECRETION, GOBP_DIGESTIVE_SYSTEM_PROCESS, GOBP_REGULATION_OF_PH, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_BODY_FLUID_SECRETION, GOBP_REGULATION_OF_BODY_FLUID_LEVELS, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT

GO Biological Process (10): bicarbonate transport (GO:0015701), sodium ion transmembrane transport (GO:0035725), saliva secretion (GO:0046541), regulation of intracellular pH (GO:0051453), transmembrane transport (GO:0055085), monoatomic ion transport (GO:0006811), monoatomic anion transport (GO:0006820), inorganic anion transport (GO:0015698), monoatomic anion transmembrane transport (GO:0098656), chloride transmembrane transport (GO:1902476)

GO Molecular Function (6): sodium:bicarbonate symporter activity (GO:0008510), sodium,bicarbonate:chloride antiporter activity (GO:0140892), chloride:bicarbonate antiporter activity (GO:0140900), solute:inorganic anion antiporter activity (GO:0005452), monoatomic anion transmembrane transporter activity (GO:0008509), antiporter activity (GO:0015297)

GO Cellular Component (4): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), apical part of cell (GO:0045177), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
SLC-mediated transport of inorganic anions1
Transport of small molecules1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
transport4
monoatomic anion transmembrane transport2
cellular anatomical structure2
sodium ion transport1
monoatomic cation transmembrane transport1
body fluid secretion1
digestive system process1
secretion by tissue1
regulation of pH1
intracellular monoatomic cation homeostasis1
regulation of biological quality1
cellular process1
monoatomic ion transport1
monoatomic anion transport1
monoatomic ion transmembrane transport1
chloride transport1
solute:sodium symporter activity1
monoatomic cation:bicarbonate symporter activity1
sodium ion transmembrane transporter activity1
metal cation:monoatomic cation antiporter activity1
chloride:bicarbonate antiporter activity1
solute:inorganic anion antiporter activity1
chloride transmembrane transporter activity1
bicarbonate:monoatomic anion antiporter activity1
antiporter activity1
monoatomic ion transmembrane transporter activity1
secondary active transmembrane transporter activity1
membrane1
cell periphery1
basal plasma membrane1
plasma membrane region1

Protein interactions and networks

STRING

700 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
SLC4A9ANKHD1Q8IWZ3716
SLC4A9ATAD1Q8NBU5648
SLC4A9SLC26A6Q9BXS9602
SLC4A9SLC26A9Q7LBE3596
SLC4A9CA2P00918592
SLC4A9CFTRP13569578
SLC4A9SLC26A4O43511577
SLC4A9SLC26A7Q8TE54570
SLC4A9GYPAP02724552
SLC4A9EIF4EBP3O60516547
SLC4A9H1-0P07305547
SLC4A9SLC26A3P40879525
SLC4A9SLC26A1Q9H2B4468
SLC4A9SLC26A11Q86WA9464
SLC4A9ATP6V1C2Q8NEY4454

IntAct

3 interactions, top by confidence:

ABTypeScore
SLC46A3CLGNpsi-mi:“MI:0914”(association)0.350
SLC4A9ILVBLpsi-mi:“MI:0914”(association)0.350

BioGRID (72): SLC4A9 (Affinity Capture-MS), ABHD3 (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), AMFR (Affinity Capture-MS), AREL1 (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), BAG3 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), BAG6 (Affinity Capture-MS), BRIX1 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), CDK4 (Affinity Capture-MS), CDKAL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, A0A494BA31, B1MTL0, B2RXE2, D3ZBP4, E9Q3M5, F1MH07, O18917, O62667, O88269, P02730, P04919, P04920, P13808, P15575, P16283, P23347, P23348, P23562, P48746, P48751, Q14940, Q14AT5, Q2Y0W8, Q32LP4, Q5DTL9, Q5RB85, Q5RD44, Q60825, Q6IFT6, Q6IWH7, Q6RI88, Q6RVG2, Q6SJP2, Q6U841, Q80ZA5, Q8JZR6, Q8K4V2, Q8NG04, Q8TDZ2

Diamond homologs: A0A096X8J7, A0A494BA31, B1MTL0, E9Q3M5, O13134, O18917, O88343, P02730, P04919, P04920, P13808, P15575, P16283, P23347, P23348, P23562, P32847, P48746, P48751, Q2Y0W8, Q32LP4, Q4U116, Q5DTL9, Q5RB85, Q5RD44, Q6RI88, Q6RVG2, Q6SJP2, Q6U841, Q80ZA5, Q8BTY2, Q8JZR6, Q8K4V2, Q96Q91, Q9BY07, Q9GKY1, Q9GL77, Q9JI66, Q9R1N3, Q9XSZ4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance102
Likely benign4
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3389 predictions. Top by Δscore:

VariantEffectΔscore
5:140360463:GCAG:Gdonor_gain1.0000
5:140360464:CAGGT:Cdonor_loss1.0000
5:140360465:AGG:Adonor_loss1.0000
5:140360467:G:GGdonor_gain1.0000
5:140362002:T:Aacceptor_gain1.0000
5:140362016:GT:Gacceptor_gain1.0000
5:140362136:G:GAdonor_gain1.0000
5:140362910:A:AGacceptor_gain1.0000
5:140362911:G:GGacceptor_gain1.0000
5:140363557:T:Adonor_loss1.0000
5:140364361:A:AGacceptor_gain1.0000
5:140364362:G:GGacceptor_gain1.0000
5:140364362:GA:Gacceptor_gain1.0000
5:140364488:A:Tdonor_gain1.0000
5:140371093:A:AGacceptor_gain1.0000
5:140371094:G:GAacceptor_gain1.0000
5:140371094:GTTC:Gacceptor_gain1.0000
5:140372381:G:GTdonor_gain1.0000
5:140372395:GAT:Gdonor_gain1.0000
5:140372717:A:AGacceptor_gain1.0000
5:140372743:A:AGacceptor_gain1.0000
5:140372744:G:GGacceptor_gain1.0000
5:140360462:GGCAG:Gdonor_gain0.9900
5:140360463:GCAGG:Gdonor_gain0.9900
5:140360464:C:Tdonor_gain0.9900
5:140360464:CAG:Cdonor_gain0.9900
5:140360465:AG:Adonor_gain0.9900
5:140360466:GG:Gdonor_gain0.9900
5:140360810:AGGTG:Aacceptor_gain0.9900
5:140360811:GGTGG:Gacceptor_gain0.9900

AlphaMissense

6174 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
5:140363864:T:CF430L0.994
5:140363866:T:AF430L0.994
5:140363866:T:GF430L0.994
5:140364135:A:CS470R0.994
5:140364137:C:AS470R0.994
5:140364137:C:GS470R0.994
5:140364508:A:CS536R0.994
5:140364510:C:AS536R0.994
5:140364510:C:GS536R0.994
5:140364138:A:CS471R0.993
5:140364140:C:AS471R0.993
5:140364140:C:GS471R0.993
5:140364066:A:CS447R0.990
5:140364068:T:AS447R0.990
5:140364068:T:GS447R0.990
5:140364493:T:CF531L0.989
5:140364495:C:AF531L0.989
5:140364495:C:GF531L0.989
5:140367795:T:AW775R0.989
5:140367795:T:CW775R0.989
5:140364163:A:TE479V0.987
5:140364478:T:CF526L0.986
5:140364480:C:AF526L0.986
5:140364480:C:GF526L0.986
5:140368596:G:CR812S0.985
5:140368596:G:TR812S0.985
5:140364075:G:CG450R0.983
5:140368615:T:CF819L0.983
5:140368617:C:AF819L0.983
5:140368617:C:GF819L0.983

dbSNP variants (sampled 300 via entrez): RS1000018389 (5:140372097 T>C), RS1000365383 (5:140358518 T>C), RS1000732942 (5:140359801 C>A), RS1000778573 (5:140367306 C>A,T), RS1000808996 (5:140369053 T>C), RS1000950469 (5:140360276 T>A,G), RS1000980817 (5:140367002 G>A), RS1001122601 (5:140362816 C>G), RS1001229584 (5:140361714 T>G), RS1001461997 (5:140375616 A>G), RS1001570050 (5:140371392 G>A), RS1001674828 (5:140365091 G>A), RS1001769583 (5:140371907 G>C), RS1001905443 (5:140373242 G>A), RS1001934300 (5:140375345 A>G)

Disease associations

OMIM: gene MIM:610207 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

StudyTraitp-value
GCST008103_180Bipolar disorder9.000000e-06
GCST008115_56Bipolar I disorder8.000000e-07

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0009963bipolar I disorder

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 — Anion exchangers

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

ChemicalActions (top 5)PubMed papers
hydroxyhydroquinonedecreases expression1
Benzo(a)pyreneaffects methylation, increases methylation1
Cadmium Chloridedecreases expression1
Okadaic Acidaffects expression1

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): bipolar disorder

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 76

This page pulls from 76 datasets indexed by BioBTree:

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