TUNAR

Summary

TUNAR (transmembrane neural differentiation associated intracellular calcium regulator, HGNC:44088) is a protein-coding gene on chromosome 14q32.2, encoding Protein TUNAR (A0A1B0GTB2). In neurons, plays a role in the regulation of intracellular Ca(2+), possibly by acting as an activator of ATP2A2/SERCA2, thus increasing the efficiency with which Ca(2+) is removed from the cytoplasm.

Enables ATPase binding activity. Involved in endoplasmic reticulum calcium ion homeostasis and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in endoplasmic reticulum.

Source: NCBI Gene 100507043 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001416131

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44088
Approved symbol	TUNAR
Name	transmembrane neural differentiation associated intracellular calcium regulator
Location	14q32.2
Locus type	gene with protein product
Status	Approved
Aliases	BNLN, TUNA, pTUNAR, HI-LNC78
Ensembl gene	ENSG00000250366
Ensembl biotype	protein_coding
OMIM	615719
Entrez	100507043

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000503525, ENST00000504119, ENST00000554321, ENST00000678517, ENST00000687554, ENST00000917015

RefSeq mRNA: 3 — MANE Select: NM_001416131 NM_001416131, NM_001416132, NM_001416133

Canonical transcript exons

ENST00000503525 — 2 exons

Exon	Start	End
ENSE00002466009	95876832	95877177
ENSE00002519913	95922781	95925571

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 93.03.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1858 / max 186.7662, expressed in 290 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141321	1.0257	175
141309	0.3490	142
141308	0.2782	132
141323	0.2650	120
141314	0.2353	90
141313	0.1967	100
141322	0.1858	94
141315	0.1319	78
141310	0.1196	61
141311	0.1016	66

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
putamen	UBERON:0001874	93.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.02	gold quality
islet of Langerhans	UBERON:0000006	91.97	gold quality
caudate nucleus	UBERON:0001873	91.95	gold quality
pons	UBERON:0000988	90.78	gold quality
nucleus accumbens	UBERON:0001882	87.45	gold quality
lateral globus pallidus	UBERON:0002476	86.37	silver quality
anterior cingulate cortex	UBERON:0009835	82.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.32	gold quality
prefrontal cortex	UBERON:0000451	82.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.79	gold quality
right frontal lobe	UBERON:0002810	81.58	gold quality
hypothalamus	UBERON:0001898	81.34	gold quality
frontal cortex	UBERON:0001870	80.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.41	gold quality
neocortex	UBERON:0001950	80.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.54	gold quality
cerebral cortex	UBERON:0000956	79.47	gold quality
forebrain	UBERON:0001890	79.42	gold quality
superior frontal gyrus	UBERON:0002661	78.23	gold quality
Ammon’s horn	UBERON:0001954	77.73	gold quality
brain	UBERON:0000955	77.68	gold quality
entorhinal cortex	UBERON:0002728	75.25	gold quality
Brodmann (1909) area 23	UBERON:0013554	74.83	silver quality
cortical plate	UBERON:0005343	74.81	gold quality
superior vestibular nucleus	UBERON:0007227	74.67	gold quality
Brodmann (1909) area 46	UBERON:0006483	74.14	gold quality
middle temporal gyrus	UBERON:0002771	73.99	silver quality
right hemisphere of cerebellum	UBERON:0014890	73.70	gold quality
medulla oblongata	UBERON:0001896	72.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• This study found the human ortholog of TUNA, linc00617, was upregulated in breast cancer samples. (PMID:26207516)
• The long noncoding RNA TUNAR modulates Wnt signaling and regulates human beta-cell proliferation. (PMID:33682459)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tunar	ENSMUSG00000097929
rattus_norvegicus		ENSRNOG00000083299

Protein

Protein identifiers

Protein TUNAR — A0A1B0GTB2 (reviewed: A0A1B0GTB2)

Alternative names: Beta cell and neural cell-regulin, TCL1 upstream neural differentiation-associated RNA

All UniProt accessions (2): A0A1B0GTB2, A0A7I2V4K3

UniProt curated annotations — full annotation on UniProt →

Function. In neurons, plays a role in the regulation of intracellular Ca(2+), possibly by acting as an activator of ATP2A2/SERCA2, thus increasing the efficiency with which Ca(2+) is removed from the cytoplasm. Inhibits differentiation of embryonic stem cells into neurons and inhibits neurite outgrowth, likely as a result of its role in intracellular Ca(2+) regulation. In pancreatic beta cells, lowers Ca(2+) levels in the endoplasmic reticulum and enhances glucose-stimulated insulin secretion.

Subunit / interactions. Interacts with ATPase ATP2A2/SERCA2. Interacts with ATPase ATP2A3/SERCA3; the interaction occurs at low levels in low glucose conditions and is increased by high glucose levels.

Subcellular location. Endoplasmic reticulum membrane. Extracellular vesicle membrane.

Tissue specificity. Highly expressed in pancreatic islets where it is enriched in the insulin-producing beta cells.

RefSeq proteins (3): NP_001403060, NP_001403061, NP_001403062 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR054138	TUNAR	Family

Pfam: PF21954

UniProt features (4 total): chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A1B0GTB2-F1	82.22	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (6): endoplasmic reticulum calcium ion homeostasis (GO:0032469), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), negative regulation of neuron differentiation (GO:0045665), neuron projection morphogenesis (GO:0048812), regulation of cytosolic calcium ion concentration (GO:0051480), nervous system development (GO:0007399)

GO Molecular Function (1): ATPase binding (GO:0051117)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular calcium ion homeostasis	2
endoplasmic reticulum	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
neuron differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
system development	1
enzyme binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

68 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUNAR	PTBP1	P26599	578
TUNAR	HNRNPK	P61978	549
TUNAR	TMEM150C	B9EJG8	372
TUNAR	DLX6	P56179	293
TUNAR	ACAA1	P09110	285
TUNAR	FAM91A1	Q658Y4	279
TUNAR	SOX2	P48431	244
TUNAR	NANOG	Q9H9S0	220
TUNAR	POU3F3	P20264	216
TUNAR	MAPK4	P31152	216
TUNAR	DLX1	P56177	215
TUNAR	PRR32	B1ATL7	210
TUNAR	PMEPA1	Q969W9	205
TUNAR	WEE2	P0C1S8	204
TUNAR	DISC1	Q9NRI5	202

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GQX2, A0A1B0GTB2, A2BUT0, A2C0D2, A6BM34, A7M911, A8W3J7, B0JYB0, B1WS50, B2J4U1, B2Y1W9, B7JV08, B7KFH4, O19926, O29047, O70901, P0C0X9, P0C179, P0DI80, P27387, P29662, P30395, P31591, P58246, Q06GN1, Q06RE7, Q06SD5, Q06SI9, Q110N3, Q1ACL7, Q28053, Q28280, Q28748, Q28757, Q29149, Q32FX5, Q3J1A4, Q3M5W2, Q46H80, Q54YR4

Diamond homologs: A0A1B0GQX2, A0A1B0GTB2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000027710 (14:95878928 A>G), RS1000049082 (14:95899717 G>C), RS1000099223 (14:95900777 G>A,T), RS1000113105 (14:95874783 G>A), RS1000187775 (14:95912372 C>T), RS1000195764 (14:95912276 T>C), RS1000213838 (14:95889004 G>A), RS1000352354 (14:95883584 C>G,T), RS1000488134 (14:95883352 A>G,T), RS1000519215 (14:95884711 C>A), RS1000623426 (14:95879313 A>G), RS1000626865 (14:95877472 G>A), RS1000705113 (14:95890104 T>C), RS1000712468 (14:95888820 T>C), RS1000741217 (14:95904997 G>A,C)

Disease associations

OMIM: gene MIM:615719 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002945_22	Emphysema imaging phenotypes	2.000000e-06
GCST002945_39	Emphysema imaging phenotypes	4.000000e-07
GCST008892_15	Working memory	3.000000e-06
GCST009066_41	Mosaic loss of chromosome Y (Y chromosome dosage)	4.000000e-18
GCST009067_32	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-106

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007626	emphysema imaging measurement
EFO:0004335	short-term memory
EFO:0007783	mosaic loss of chromosome Y measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 0 entries

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Copper	affects cotreatment, decreases expression	1
Phenylmercuric Acetate	decreases expression	1
Tretinoin	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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