AQP12A

Summary

AQP12A (aquaporin 12A, HGNC:19941) is a protein-coding gene on chromosome 2q37.3, encoding Putative aquaporin-12A (Q8IXF9). 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 375318 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total — 2 pathogenic
• MANE Select transcript: NM_198998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19941
Approved symbol	AQP12A
Name	aquaporin 12A
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000184945
Ensembl biotype	protein_coding
OMIM	609789
Entrez	375318

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000337801, ENST00000460527, ENST00000471878, ENST00000474778

RefSeq mRNA: 1 — MANE Select: NM_198998 NM_198998

Canonical transcript exons

ENST00000337801 — 4 exons

Exon	Start	End
ENSE00002299809	240692074	240692521
ENSE00002306648	240691866	240692036
ENSE00002520255	240694433	240694549
ENSE00003680002	240698157	240698483

Expression profiles

Bgee: expression breadth broad, 84 present calls, max score 98.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1060 / max 95.9452, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26454	0.1060	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.49	gold quality
pancreas	UBERON:0001264	79.00	gold quality
duodenum	UBERON:0002114	61.20	gold quality
transverse colon	UBERON:0001157	58.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	58.02	gold quality
small intestine	UBERON:0002108	57.78	gold quality
mucosa of transverse colon	UBERON:0004991	57.61	gold quality
intestine	UBERON:0000160	53.23	gold quality
colon	UBERON:0001155	52.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	46.20	gold quality
vermiform appendix	UBERON:0001154	45.87	gold quality
rectum	UBERON:0001052	45.58	gold quality
colonic epithelium	UBERON:0000397	43.16	gold quality
fundus of stomach	UBERON:0001160	41.32	gold quality
islet of Langerhans	UBERON:0000006	40.34	gold quality
right coronary artery	UBERON:0001625	40.20	silver quality
endocervix	UBERON:0000458	39.63	gold quality
left lobe of thyroid gland	UBERON:0001120	37.10	gold quality
skeletal muscle tissue	UBERON:0001134	36.80	silver quality
tonsil	UBERON:0002372	36.68	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
thyroid gland	UBERON:0002046	36.38	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
muscle tissue	UBERON:0002385	35.70	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
placenta	UBERON:0001987	35.40	gold quality
temporal lobe	UBERON:0001871	34.81	gold quality
right lobe of liver	UBERON:0001114	34.66	silver quality
right uterine tube	UBERON:0001302	34.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	20.09
E-ANND-3	yes	18.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting AQP12A, 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-299-5P	98.56	71.14	1140
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-4508	90.37	59.62	240

Literature-anchored findings (GeneRIF, showing 3)

• a role of AQP12 in digestive enzyme secretion such as maturation and exocytosis of secretory granules (PMID:15809071)
• Built accurate 3D-models for AQP11 and AQP12 and comprehensively compared their sequence and structure to other known aquaporins. (PMID:23359558)
• 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), AQP12B (ENSG00000185176)

Protein

Protein identifiers

Putative aquaporin-12A — Q8IXF9 (reviewed: Q8IXF9)

All UniProt accessions (1): Q8IXF9

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.

Tissue specificity. Restricted to the pancreas.

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.

RefSeq proteins (1): NP_945349* (*=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 (18 total): transmembrane region 6, topological domain 6, intramembrane region 2, short sequence motif 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXF9-F1	78.38	0.33

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-432047	Passive transport by Aquaporins
R-HSA-382551	Transport of small molecules
R-HSA-445717	Aquaporin-mediated transport

MSigDB gene sets: 28 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_WATER_TRANSPORT, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_FLUID_TRANSPORT, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_WATER_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_TRANSPORT_OF_SMALL_MOLECULES, GSE10239_MEMORY_VS_KLRG1INT_EFF_CD8_TCELL_UP, GSE10239_MEMORY_VS_KLRG1HIGH_EFF_CD8_TCELL_UP, GSE13306_RA_VS_UNTREATED_TCONV_UP, chr2q37, DESCARTES_FETAL_PANCREAS_ACINAR_CELLS

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

GO Molecular Function (2): water channel activity (GO:0015250), channel activity (GO:0015267)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aquaporin-mediated transport	1
Transport of small molecules	1

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
intracellular anatomical structure	1

Protein interactions and networks

STRING

582 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AQP12A	MIP	P30301	899
AQP12A	AQP10	Q96PS8	891
AQP12A	AQP6	Q13520	888
AQP12A	AQP8	O94778	887
AQP12A	AQP7	O14520	858
AQP12A	AQP5	P55064	816
AQP12A	AQP3	Q92482	792
AQP12A	AQP2	P41181	750
AQP12A	AQP9	O43315	695
AQP12A	AQP1	P29972	556
AQP12A	KRTAP5-10	Q6L8G5	393
AQP12A	AQP11	Q8NBQ7	316
AQP12A	UBA2	Q9UBT2	278
AQP12A	TEX261	Q6UWH6	269
AQP12A	AVP	P01185	267

IntAct

0 interactions, top by confidence:

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

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	50
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
144756	GRCh38/hg38 2q36.3-37.3(chr2:228723579-241404867)x3	Pathogenic
57432	GRCh38/hg38 2q37.3(chr2:237643996-242126245)x1	Pathogenic

SpliceAI

707 predictions. Top by Δscore:

Variant	Effect	Δscore
2:240692519:CGGGT:C	donor_loss	0.9900
2:240692520:GG:G	donor_gain	0.9900
2:240692521:GG:G	donor_gain	0.9900
2:240692521:GGTGA:G	donor_loss	0.9900
2:240692522:GTG:G	donor_loss	0.9900
2:240692523:T:G	donor_loss	0.9900
2:240692522:G:GG	donor_gain	0.9800
2:240694431:AGCCG:A	acceptor_gain	0.9800
2:240694432:GCC:G	acceptor_gain	0.9800
2:240694432:GCCGG:G	acceptor_gain	0.9800
2:240697858:G:GT	donor_gain	0.9800
2:240698155:AG:A	acceptor_gain	0.9800
2:240698155:AGG:A	acceptor_gain	0.9800
2:240698156:GG:G	acceptor_gain	0.9800
2:240698156:GGG:G	acceptor_gain	0.9800
2:240698156:GGGAT:G	acceptor_gain	0.9800
2:240692524:GA:G	donor_loss	0.9700
2:240694431:A:AG	acceptor_gain	0.9700
2:240694431:AGCC:A	acceptor_gain	0.9700
2:240694432:G:GG	acceptor_gain	0.9700
2:240694432:GCCG:G	acceptor_gain	0.9700
2:240694469:T:TA	acceptor_gain	0.9700
2:240696600:G:GT	donor_gain	0.9700
2:240698151:TTGCA:T	acceptor_loss	0.9700
2:240698152:TGCA:T	acceptor_loss	0.9700
2:240698153:GCA:G	acceptor_loss	0.9700
2:240698154:CA:C	acceptor_loss	0.9700
2:240698155:A:AG	acceptor_gain	0.9700
2:240698155:A:AT	acceptor_loss	0.9700
2:240698156:G:GG	acceptor_gain	0.9700

AlphaMissense

1872 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:240694461:C:A	N200K	0.916
2:240694461:C:G	N200K	0.916
2:240692412:G:C	E154D	0.905
2:240692412:G:T	E154D	0.905
2:240692411:A:T	E154V	0.903
2:240692193:C:A	N81K	0.900
2:240692193:C:G	N81K	0.900
2:240694486:T:C	F209L	0.866
2:240694488:T:A	F209L	0.866
2:240694488:T:G	F209L	0.866
2:240694453:T:C	F198L	0.864
2:240694455:C:A	F198L	0.864
2:240694455:C:G	F198L	0.864
2:240698204:T:C	F246L	0.860
2:240698206:C:A	F246L	0.860
2:240698206:C:G	F246L	0.860
2:240694549:G:T	G230W	0.846
2:240694537:G:C	G226R	0.839
2:240692398:G:T	G150W	0.819
2:240692143:T:C	F65L	0.815
2:240692145:C:A	F65L	0.815
2:240692145:C:G	F65L	0.815
2:240694531:T:A	W224R	0.812
2:240694531:T:C	W224R	0.812
2:240698169:C:A	A234D	0.804
2:240694549:G:A	G230R	0.800
2:240694549:G:C	G230R	0.800
2:240694445:C:A	T195K	0.796
2:240694472:C:A	A204D	0.792
2:240698161:G:A	M231I	0.790

dbSNP variants (sampled 300 via entrez): RS1000386554 (2:240691304 C>G), RS1000478412 (2:240690875 G>A), RS1002467060 (2:240695094 C>T), RS1002496752 (2:240696464 C>T), RS1004187480 (2:240691660 G>A), RS1004281052 (2:240691383 G>A,C), RS1004523859 (2:240689994 G>T), RS1008645376 (2:240690838 T>C), RS1008723516 (2:240692703 T>C), RS1011243895 (2:240693299 A>G), RS1011899861 (2:240694409 G>C), RS1013159240 (2:240691344 G>T), RS1015644128 (2:240691386 G>C), RS1015841998 (2:240689999 C>T), RS10166794 (2:240694614 G>A)

Disease associations

OMIM: gene MIM:609789 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Diazinon	decreases methylation	1
Malathion	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders