AQP12B

Summary

AQP12B (aquaporin 12B, HGNC:6096) is a protein-coding gene on chromosome 2q37.3, encoding Putative aquaporin-12B (A6NM10). Putative aquaporin.

Predicted to enable channel activity. Predicted to be involved in transmembrane transport and water transport. Predicted to be located in membrane. Predicted to be active in cytoplasm.

Source: NCBI Gene 653437 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 85 total — 1 pathogenic
• MANE Select transcript: NM_001102467

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6096
Approved symbol	AQP12B
Name	aquaporin 12B
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185176
Ensembl biotype	protein_coding
Entrez	653437

Gene structure

Transcript identifiers

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

ENST00000407834, ENST00000413999, ENST00000414322, ENST00000452886, ENST00000459806, ENST00000621682

RefSeq mRNA: 1 — MANE Select: NM_001102467 NM_001102467

CCDS: CCDS46560

Canonical transcript exons

ENST00000407834 — 3 exons

Exon	Start	End
ENSE00001558453	240682231	240682885
ENSE00001823919	240676418	240676744
ENSE00003494465	240680352	240680468

Expression profiles

Bgee: expression breadth broad, 82 present calls, max score 99.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1307 / max 152.3835, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34840	0.1307	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	99.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.51	gold quality
pancreas	UBERON:0001264	80.95	gold quality
duodenum	UBERON:0002114	66.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	60.82	gold quality
transverse colon	UBERON:0001157	60.60	gold quality
small intestine	UBERON:0002108	59.74	gold quality
small intestine Peyer’s patch	UBERON:0003454	59.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	59.59	gold quality
colon	UBERON:0001155	58.93	gold quality
intestine	UBERON:0000160	58.59	gold quality
mucosa of transverse colon	UBERON:0004991	54.90	gold quality
rectum	UBERON:0001052	50.44	gold quality
anterior cingulate cortex	UBERON:0009835	47.80	gold quality
lymph node	UBERON:0000029	45.75	gold quality
islet of Langerhans	UBERON:0000006	45.43	gold quality
endocervix	UBERON:0000458	44.68	gold quality
right frontal lobe	UBERON:0002810	43.46	gold quality
bone marrow cell	CL:0002092	43.32	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	43.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	43.10	gold quality
vermiform appendix	UBERON:0001154	42.78	gold quality
fundus of stomach	UBERON:0001160	42.39	gold quality
sural nerve	UBERON:0015488	42.31	gold quality
frontal cortex	UBERON:0001870	42.28	gold quality
colonic epithelium	UBERON:0000397	42.18	gold quality
cerebral cortex	UBERON:0000956	42.12	gold quality
apex of heart	UBERON:0002098	41.75	silver quality
right lobe of liver	UBERON:0001114	41.30	silver quality
prefrontal cortex	UBERON:0000451	40.99	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	22.17
E-ANND-3	yes	17.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting AQP12B, 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-5680	99.91	69.83	3421
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-4508	90.37	59.62	240

Literature-anchored findings (GeneRIF, showing 1)

• Genetic analysis of the aquaporin water channels AQP12A and AQP12B in patients with chronic pancreatitis. (PMID:36167651)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	aqp12	ENSDARG00000043279
mus_musculus	Aqp12	ENSMUSG00000045091
rattus_norvegicus	Aqp12a	ENSRNOG00000004452
drosophila_melanogaster	AQP	FBGN0033807
caenorhabditis_elegans	aqp-9	WBGENE00000177
caenorhabditis_elegans		WBGENE00000178
caenorhabditis_elegans		WBGENE00000179

Paralogs (2): AQP11 (ENSG00000178301), AQP12A (ENSG00000184945)

Protein

Protein identifiers

Putative aquaporin-12B — A6NM10 (reviewed: A6NM10)

All UniProt accessions (2): A6NM10, F2Z3N0

UniProt curated annotations — full annotation on UniProt →

Function. Putative aquaporin. Could form homotetrameric transmembrane channels, with each monomer independently mediating water transport across the plasma membrane along its osmotic gradient.

Subunit / interactions. Homotetramer; each monomer provides an independent water pore.

Subcellular location. Membrane.

Domain organisation. Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).

Similarity. Belongs to the MIP/aquaporin (TC 1.A.8) family. AQP11/AQP12 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NM10-1	1	yes
A6NM10-2	2

RefSeq proteins (1): NP_001095937* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000425	MIP	Family
IPR016697	Aquaporin_11/12	Family
IPR023265	Aquaporin_12	Family
IPR023271	Aquaporin-like	Homologous_superfamily
IPR051883	AQP11/12_channel	Family

Pfam: PF00230

Catalyzed reactions (Rhea), 1 shown:

• H2O(in) = H2O(out) (RHEA:29667)

UniProt features (22 total): topological domain 9, transmembrane region 6, intramembrane region 2, short sequence motif 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NM10-F1	80.14	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 10 (showing top): GOBP_WATER_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_FLUID_TRANSPORT, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_WATER_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, chr2q37, MATSUMIYA_PBMC_MODIFIED_VACCINIA_ANKARA_VACCINE_AGE_18_55YO_VACCINATED_VS_CONTROL_TREATED_IN_VITRO_WITH_WILD_TYPE_MVA_6HR_UP, WP_2Q37_COPY_NUMBER_VARIATION_SYNDROME, GOMF_WATER_CHANNEL_ACTIVITY

GO Biological Process (2): water transport (GO:0006833), transmembrane transport (GO:0055085)

GO Molecular Function (3): water channel activity (GO:0015250), channel activity (GO:0015267), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
fluid transport	1
transport	1
cellular process	1
water transmembrane transporter activity	1
channel activity	1
passive transmembrane transporter activity	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AQP12B	AQP6	Q13520	587
AQP12B	AQP10	Q96PS8	545
AQP12B	AQP7	O14520	523
AQP12B	MIP	P30301	523
AQP12B	KRTAP5-10	Q6L8G5	512
AQP12B	AQP8	O94778	498
AQP12B	AQP3	Q92482	458
AQP12B	AQP5	P55064	456
AQP12B	SMIM10L2A	P0DMW4	445
AQP12B	TEX261	Q6UWH6	420
AQP12B	AQP9	O43315	419
AQP12B	SPAG7	O75391	392
AQP12B	KRTAP5-11	Q6L8G4	382
AQP12B	AQP1	P29972	381
AQP12B	TMEM187	Q14656	364

IntAct

3 interactions, top by confidence:

A	B	Type	Score
AQP12B	SEMG1	psi-mi:“MI:0914”(association)	0.350
AQP12B	TIPRL	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): AQP12B (Two-hybrid), AQP12B (Two-hybrid), AQP12B (Two-hybrid), LOC100507537 (Two-hybrid), POF1B (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PEX5 (Affinity Capture-MS), SERPINB2 (Affinity Capture-MS), FLG (Affinity Capture-MS), KIAA0368 (Affinity Capture-MS), JUP (Affinity Capture-MS), PCCA (Affinity Capture-MS), PCCB (Affinity Capture-MS)

ESM2 similar proteins: A2AE42, A3A9H6, A5D7C9, A5D9A7, A6NM10, B3SHH9, B5DFH9, B9EJG8, F1NZP5, O14569, P10897, P49447, P82352, Q08DE1, Q14714, Q148G2, Q3ZCD2, Q5E965, Q5ND56, Q5RCZ2, Q5U2W7, Q5ZJX0, Q60720, Q62147, Q641Y1, Q6GPL4, Q6P0C6, Q6P1H1, Q71RH2, Q7TNV1, Q80ZE4, Q86TG1, Q8BMD6, Q8C8S3, Q8IXF9, Q8N8Q1, Q8NBI2, Q8TBR7, Q8VHW3, Q8VHW7

Diamond homologs: A6NM10, F6S3G9, Q8CHJ2, Q8CHM1, Q8IXF9, Q8NBQ7, Q8BHH1, Q10M80, Q9ATM1, Q9ATM3, Q9M1K3, Q9V5Z7, V6RVB4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	74
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
816582	GRCh37/hg19 2q36.3-37.3(chr2:230814690-242783384)x3	Pathogenic

SpliceAI

823 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240678300:G:GA	donor_gain	0.9900
2:240682225:GCTCA:G	donor_loss	0.9900
2:240682226:CTCA:C	donor_loss	0.9900
2:240682227:TCA:T	donor_loss	0.9900
2:240682228:CACC:C	donor_loss	0.9900
2:240682229:A:T	donor_loss	0.9900
2:240682229:AC:A	donor_gain	0.9900
2:240682230:CC:C	donor_gain	0.9900
2:240676743:CC:C	acceptor_gain	0.9800
2:240676744:CC:C	acceptor_gain	0.9800
2:240677042:C:CA	donor_gain	0.9800
2:240678323:A:C	donor_gain	0.9800
2:240680464:CCCGG:C	acceptor_gain	0.9800
2:240680465:CCGGC:C	acceptor_gain	0.9800
2:240680466:CGG:C	acceptor_gain	0.9800
2:240682229:A:AC	donor_gain	0.9800
2:240682230:C:CC	donor_gain	0.9800
2:240676740:CATCC:C	acceptor_gain	0.9700
2:240676742:TCC:T	acceptor_gain	0.9700
2:240676743:CCC:C	acceptor_gain	0.9700
2:240676745:C:CC	acceptor_gain	0.9700
2:240678297:ACGG:A	donor_gain	0.9700
2:240678298:CGGC:C	donor_gain	0.9700
2:240680431:C:CT	acceptor_gain	0.9700
2:240680469:C:CC	acceptor_gain	0.9700
2:240676746:T:A	acceptor_loss	0.9600
2:240680465:CCGG:C	acceptor_gain	0.9600
2:240680466:CGGC:C	acceptor_gain	0.9600
2:240682229:ACC:A	donor_gain	0.9600
2:240682230:CCC:C	donor_gain	0.9600

AlphaMissense

1944 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240680440:G:C	N200K	0.937
2:240680440:G:T	N200K	0.937
2:240682341:T:A	E154V	0.911
2:240682340:C:A	E154D	0.907
2:240682340:C:G	E154D	0.907
2:240682559:G:C	N81K	0.904
2:240682559:G:T	N81K	0.904
2:240680413:A:C	F209L	0.872
2:240680413:A:T	F209L	0.872
2:240680415:A:G	F209L	0.872
2:240680446:G:C	F198L	0.869
2:240680446:G:T	F198L	0.869
2:240680448:A:G	F198L	0.869
2:240676695:G:C	F246L	0.867
2:240676695:G:T	F246L	0.867
2:240676697:A:G	F246L	0.867
2:240680352:C:A	G230W	0.862
2:240680364:C:G	G226R	0.850
2:240682354:C:A	G150W	0.841
2:240682439:C:A	W121C	0.835
2:240682439:C:G	W121C	0.835
2:240680370:A:G	W224R	0.821
2:240680370:A:T	W224R	0.821
2:240680429:G:T	A204D	0.816
2:240680456:G:T	T195K	0.814
2:240682808:G:C	F10L	0.814
2:240682808:G:T	F10L	0.814
2:240682810:A:G	F10L	0.814
2:240676740:C:A	M231I	0.806
2:240676740:C:G	M231I	0.806

dbSNP variants (sampled 300 via entrez): RS1001594777 (2:240683310 C>G), RS1001995166 (2:240681172 G>A), RS1002057011 (2:240683896 C>T), RS1002328395 (2:240679923 A>G), RS1004705776 (2:240684456 C>A), RS1005242043 (2:240684196 A>T), RS1006714584 (2:240678327 C>T), RS1007259916 (2:240676161 G>A), RS1008533394 (2:240684788 G>C), RS1009193076 (2:240685672 G>A), RS1010460768 (2:240683816 C>G,T), RS1010552337 (2:240679880 G>C), RS1010636868 (2:240683074 C>G,T), RS1011210206 (2:240681158 G>A), RS1013104767 (2:240685741 G>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

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)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	increases methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Fluorouracil	decreases expression	1
Valproic Acid	increases methylation	1
Zinc	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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