SPAAR

Summary

SPAAR (small regulatory polypeptide of amino acid response, HGNC:27244) is a protein-coding gene on chromosome 9p13.3, encoding Small regulatory polypeptide of amino acid response (A0A1B0GVQ0). Negative regulator of amino acid sensing and mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels and amino acids.

Involved in cellular response to amino acid stimulus and negative regulation of TORC1 signaling. Located in late endosome membrane and lysosomal proton-transporting V-type ATPase complex.

Source: NCBI Gene 158376 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001348107

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27244
Approved symbol	SPAAR
Name	small regulatory polypeptide of amino acid response
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SPAR
Ensembl gene	ENSG00000235387
Ensembl biotype	protein_coding
OMIM	617627
Entrez	158376

Gene structure

Transcript identifiers

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

ENST00000433838, ENST00000443779, ENST00000636776, ENST00000638062, ENST00000650257, ENST00000958120

RefSeq mRNA: 1 — MANE Select: NM_001348107 NM_001348107

CCDS: CCDS94407

Canonical transcript exons

ENST00000443779 — 2 exons

Exon	Start	End
ENSE00001789136	35910157	35911686
ENSE00003890546	35909490	35909564

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 88.55.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6760 / max 36.0868, expressed in 257 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96647	0.3839	171
96648	0.2239	99
96646	0.0682	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	88.55	gold quality
apex of heart	UBERON:0002098	86.27	gold quality
germinal epithelium of ovary	UBERON:0001304	85.12	silver quality
omental fat pad	UBERON:0010414	83.56	gold quality
peritoneum	UBERON:0002358	83.52	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.86	gold quality
heart left ventricle	UBERON:0002084	82.26	gold quality
cardiac ventricle	UBERON:0002082	81.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.69	silver quality
gingiva	UBERON:0001828	80.53	gold quality
epithelium of nasopharynx	UBERON:0001951	79.15	gold quality
subcutaneous adipose tissue	UBERON:0002190	79.05	gold quality
adipose tissue	UBERON:0001013	78.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.02	gold quality
heart	UBERON:0000948	77.82	gold quality
right testis	UBERON:0004534	77.52	gold quality
lower lobe of lung	UBERON:0008949	77.23	silver quality
left testis	UBERON:0004533	76.74	gold quality
superficial temporal artery	UBERON:0001614	76.55	silver quality
testis	UBERON:0000473	75.62	gold quality
right atrium auricular region	UBERON:0006631	75.37	gold quality
cardiac atrium	UBERON:0002081	75.26	gold quality
upper lobe of lung	UBERON:0008948	75.00	gold quality
upper lobe of left lung	UBERON:0008952	74.87	gold quality
heart right ventricle	UBERON:0002080	74.56	gold quality
muscle of leg	UBERON:0001383	74.55	gold quality
gastrocnemius	UBERON:0001388	74.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.26	gold quality
metanephros cortex	UBERON:0010533	73.67	gold quality
right lung	UBERON:0002167	73.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.74

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 15)

• data provide a mechanism by which mTORC1 activation may be finely regulated in a tissue-specific manner in response to injury, and a paradigm by which lncRNAs encoding small polypeptides like SPAR can modulate general biological pathways and processes to facilitate tissue-specific requirements, consistent with their restricted and highly regulated expression profile (PMID:28024296)
• decreased LINC00961 might play a key role in non-small cell lung cancer (NSCLC) progression, and may serve as a novel prognostic marker in human NSCLC (PMID:29156520)
• Overexpression of LINC00961 significantly suppressed glioma cells proliferation, migration, and invasion. Mechanistically, we found that overexpression of LINC00961 inhibited glioma cell epithelial-mesenchymal transition . (PMID:30070327)
• LINC00961 is involved in renal cell carcinoma progression by targeting the epithelial-mesenchymal transition pathway. (PMID:30367453)
• Functionally, LINC00961 overexpression obviously inhibited cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Mechanistically, LINC00961 regulated cardiolipin synthase 1 expression via sponging miR-5581-3p. (PMID:30825207)
• Long noncoding RNA LINC00961 inhibited cell proliferation and invasion through regulating the Wnt/beta-catenin signaling pathway in tongue squamous cell carcinoma. (PMID:30854692)
• STAT1-avtiviated LINC00961 regulates myocardial infarction by the PI3K/AKT/GSK3beta signaling pathway. (PMID:30887575)
• LINC00961 suppresses cell proliferation and induces cell apoptosis in oral squamous cell carcinoma. (PMID:31081090)
• Study revealed that Linc00961 was downregulated in skin melanoma (SM), and was identified as a ceRNA that inhibits the proliferation and invasion of SM cell lines by modulating the miR367/PTEN axis. (PMID:31364744)
• Downregulation of linc00961 contributes to promote proliferation and inhibit apoptosis of vascular smooth muscle cell by sponging miR-367 in patients with coronary heart disease. (PMID:31646586)
• The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function. (PMID:31990292)
• LINC00961 inhibits the migration and invasion of colon cancer cells by sponging miR-223-3p and targeting SOX11. (PMID:32045135)
• Evolutionary Characterization of the Short Protein SPAAR. (PMID:34946813)
• Dysregulated LINC00961 Contributes to the Vitality and Migration of NSCLC Via miR-19a-3p/miR-19b-3p/miR-125b-5p. (PMID:35244469)
• LncRNA LINC00961 regulates endothelialmesenchymal transition via the PTENPI3KAKT pathway. (PMID:35656895)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spaar	ENSMUSG00000028475
rattus_norvegicus	Spaar	ENSRNOG00000070391

Protein

Protein identifiers

Small regulatory polypeptide of amino acid response — A0A1B0GVQ0 (reviewed: A0A1B0GVQ0)

All UniProt accessions (1): A0A1B0GVQ0

UniProt curated annotations — full annotation on UniProt →

Function. Negative regulator of amino acid sensing and mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels and amino acids. Negatively regulates mTORC1 activation by inhibiting recruitment of mTORC1 to lysosomes upon stimulation with amino acids: acts by promoting the formation of a tightly bound supercomplex composed of the lysosomal V-ATPase, Ragulator and Rag GTPases, preventing recruitment of mTORC1. Acts as a regulator of muscle regeneration following injury by regulating mTORC1 activation.

Subunit / interactions. Interacts with components of the lysosomal V-ATPase complex. Interacts with ATP6V0A1. Interacts with ATP6V0A2.

Subcellular location. Late endosome membrane. Lysosome membrane.

Tissue specificity. Highly expressed in lung, heart and skeletal muscle.

Isoforms (2)

UniProt ID	Names	Canonical?
A0A1B0GVQ0-1	1	yes
A0A1B0GVQ0-2	2

RefSeq proteins (1): NP_001335036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR054161	SPAR	Family

Pfam: PF22004

UniProt features (5 total): topological domain 2, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A1B0GVQ0-F1	67.18	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOCC_VACUOLAR_MEMBRANE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOBP_REGENERATION, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_TOR_SIGNALING, chr9p13, GOBP_TISSUE_REGENERATION, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_TOR_SIGNALING, GOCC_LATE_ENDOSOME_MEMBRANE, GOBP_REGULATION_OF_GROWTH

GO Biological Process (3): regulation of skeletal muscle tissue regeneration (GO:0043416), cellular response to amino acid stimulus (GO:0071230), negative regulation of TORC1 signaling (GO:1904262)

GO Molecular Function (0):

GO Cellular Component (6): lysosomal membrane (GO:0005765), late endosome membrane (GO:0031902), lysosome (GO:0005764), endosome (GO:0005768), membrane (GO:0016020), lysosomal proton-transporting V-type ATPase complex (GO:0046611)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of response to external stimulus	1
skeletal muscle tissue regeneration	1
regulation of developmental growth	1
regulation of multicellular organismal development	1
response to amino acid	1
cellular response to acid chemical	1
negative regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
lysosome	1
lytic vacuole membrane	1
late endosome	1
endosome membrane	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1
lysosomal membrane	1
vacuolar proton-transporting V-type ATPase complex	1

Protein interactions and networks

STRING

138 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPAAR	MRLN	P0DMT0	691
SPAAR	STRIT1	P0DN84	666
SPAAR	HRCT1	Q6UXD1	605
SPAAR	SMIM38	A0A286YFK9	592
SPAAR	TMDD1	P0DPE3	570
SPAAR	FAM240C	A0A1B0GVR7	529
SPAAR	NBDY	A0A0U1RRE5	526
SPAAR	MIEF1	L0R8F8	475
SPAAR	TMEM8B	A6NDV4	474
SPAAR	SMIM28	A0A1B0GU29	448
SPAAR	FAM221B	A6H8Z2	446
SPAAR	MYMX	A0A1B0GTQ4	423
SPAAR	Q6ZT62	Q6ZT62	398
SPAAR	MTLN	Q8NCU8	398
SPAAR	ASDURF	L0R819	393

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GRQ0, A0A1B0GSN8, A0A1B0GSZ0, A0A1B0GVQ0, A0A1B0GVT2, A0A1B0GWG4, A2A2V5, A2A9G7, A2APA5, A2VE22, A6NFZ4, A6QQ93, A7E1Z1, A7MB05, A9CBA0, B7ZWI3, D3ZR35, E9Q942, F5HAK6, F5HFG3, O14668, O39519, O39920, P09312, P0DJ93, P18345, P86045, Q2KIK3, Q498C7, Q5RCB6, Q5RF07, Q5RF75, Q67593, Q68D42, Q6AXS2, Q6UWT2, Q77NN6, Q7M750, Q80WK2, Q8BGN6

Diamond homologs: A0A1B0GSZ0, A0A1B0GVQ0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK5	“down-regulates quantity by destabilization”	SPAAR	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

3 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): RS1000979633 (9:35909999 C>A,T), RS1001431638 (9:35909642 C>T), RS1001578630 (9:35908641 T>C), RS1002525562 (9:35907585 G>A,C), RS1002631043 (9:35909424 T>C,G), RS1003167413 (9:35908282 T>A,C), RS1004749226 (9:35910240 G>A), RS1005700706 (9:35909307 C>T), RS1005751516 (9:35909036 G>A), RS1005830590 (9:35908065 A>G), RS1006052971 (9:35909399 G>T), RS1006131947 (9:35908241 C>T), RS1006702506 (9:35907959 C>G), RS1006754907 (9:35907721 C>G), RS1007299193 (9:35907932 C>T)

Disease associations

OMIM: gene MIM:617627 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90000025_470	Appendicular lean mass	7.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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