ADISSP

Summary

ADISSP (adipose secreted signaling protein, HGNC:15873) is a protein-coding gene on chromosome 20p13, encoding Adipose-secreted signaling protein (Q9GZN8). Adipocyte-secreted protein (adipokine) that acts as a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis at least in part through activation of protein kinase A (PKA).

Enables protein phosphatase 1 binding activity. Involved in positive regulation of non-canonical NF-kappaB signal transduction and positive regulation of transforming growth factor beta receptor signaling pathway. Predicted to be located in extracellular space.

Source: NCBI Gene 54976 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 11 total — 1 pathogenic
• MANE Select transcript: NM_001258429

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15873
Approved symbol	ADISSP
Name	adipose secreted signaling protein
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20550
Ensembl gene	ENSG00000101220
Ensembl biotype	protein_coding
OMIM	620373
Entrez	54976

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000217195, ENST00000379772, ENST00000399672, ENST00000399683, ENST00000888333, ENST00000888334, ENST00000888335, ENST00000888336, ENST00000888337, ENST00000936143, ENST00000936144, ENST00000936145, ENST00000936146, ENST00000936147, ENST00000948129

RefSeq mRNA: 3 — MANE Select: NM_001258429 NM_001039140, NM_001258429, NM_001258430

CCDS: CCDS33436, CCDS58763

Canonical transcript exons

ENST00000379772 — 6 exons

Exon	Start	End
ENSE00000657899	3754397	3754519
ENSE00001482401	3760082	3760186
ENSE00001814244	3767663	3767753
ENSE00002994527	3758536	3758678
ENSE00003152408	3755469	3755607
ENSE00003903109	3753508	3754158

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 98.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.7162 / max 3421.2063, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186167	50.4550	1821
186168	2.9614	1447
186166	0.2997	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	98.45	gold quality
caudate nucleus	UBERON:0001873	98.07	gold quality
putamen	UBERON:0001874	97.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.95	gold quality
granulocyte	CL:0000094	96.36	gold quality
right ovary	UBERON:0002118	95.72	gold quality
left uterine tube	UBERON:0001303	95.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.26	gold quality
lower esophagus	UBERON:0013473	95.25	gold quality
left ovary	UBERON:0002119	95.01	gold quality
decidua	UBERON:0002450	94.18	gold quality
monocyte	CL:0000576	94.14	gold quality
leukocyte	CL:0000738	94.05	gold quality
mononuclear cell	CL:0000842	94.05	gold quality
anterior cingulate cortex	UBERON:0009835	93.70	gold quality
cingulate cortex	UBERON:0003027	93.63	gold quality
omental fat pad	UBERON:0010414	93.51	gold quality
peritoneum	UBERON:0002358	93.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.21	gold quality
body of uterus	UBERON:0009853	93.14	gold quality
right frontal lobe	UBERON:0002810	92.82	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.77	gold quality
right uterine tube	UBERON:0001302	92.65	gold quality
stromal cell of endometrium	CL:0002255	92.12	gold quality
prefrontal cortex	UBERON:0000451	92.04	gold quality
amygdala	UBERON:0001876	91.92	gold quality
apex of heart	UBERON:0002098	91.79	gold quality
hypothalamus	UBERON:0001898	91.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.69	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	131.17
E-MTAB-10287	yes	100.67
E-MTAB-6678	yes	26.73
E-CURD-122	yes	10.88
E-CURD-112	yes	10.31
E-CURD-88	yes	8.96
E-MTAB-9801	yes	7.96
E-ANND-3	yes	7.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting ADISSP, 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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-181A-2-3P	98.91	67.60	1168

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ADISSP	ENSDARG00000076239
danio_rerio	adissp	ENSDARG00000087426
mus_musculus	Adissp	ENSMUSG00000027327
rattus_norvegicus	Adissp	ENSRNOG00000021245
drosophila_melanogaster	CG6983	FBGN0035896

Protein

Protein identifiers

Adipose-secreted signaling protein — Q9GZN8 (reviewed: Q9GZN8)

All UniProt accessions (2): Q9GZN8, H7BYU9

UniProt curated annotations — full annotation on UniProt →

Function. Adipocyte-secreted protein (adipokine) that acts as a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis at least in part through activation of protein kinase A (PKA).

Subcellular location. Secreted.

Similarity. Belongs to the ADISSP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9GZN8-1	1	yes
Q9GZN8-2	2

RefSeq proteins (3): NP_001034229, NP_001245358, NP_001245359 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026794	ADISSP	Family

Pfam: PF15006

UniProt features (6 total): modified residue 2, initiator methionine 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZN8-F1	80.45	0.49

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 147

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): RNGTGGGC_UNKNOWN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_POSITIVE_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (5): obsolete positive regulation of protein kinase A signaling (GO:0010739), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), glucose homeostasis (GO:0042593), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), adaptive thermogenesis (GO:1990845)

GO Molecular Function (1): protein phosphatase 1 binding (GO:0008157)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cellular_component (GO:0005575), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
carbohydrate homeostasis	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
temperature homeostasis	1
protein phosphatase binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADISSP	DMWD	Q09019	627
ADISSP	SEC24C	P53992	595
ADISSP	BRK1	Q8WUW1	594
ADISSP	HIP1R	O75146	577
ADISSP	JCAD	Q9P266	552
ADISSP	SWAP70	Q9UH65	548
ADISSP	CPNE1	Q99829	528
ADISSP	TOR4A	Q9NXH8	518
ADISSP	PCYT2	Q99447	513
ADISSP	TPM3	P06753	474
ADISSP	ATG3	Q9NT62	441
ADISSP	PSME3	P61289	376
ADISSP	QSER1	Q2KHR3	376
ADISSP	HEBP1	Q9NRV9	370
ADISSP	ATAD3B	Q5T9A4	357

IntAct

25 interactions, top by confidence:

A	B	Type	Score
PPP1CA	PPP1CC	psi-mi:“MI:0914”(association)	0.850
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	PQBP1	psi-mi:“MI:0914”(association)	0.510
PPP1R7	CCDC85C	psi-mi:“MI:0914”(association)	0.510
ADISSP	rep	psi-mi:“MI:0915”(physical association)	0.370
PHKB	ADISSP	psi-mi:“MI:0915”(physical association)	0.370
ADISSP	RALYL	psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	RPLP2	psi-mi:“MI:0914”(association)	0.350
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.350
FAM133A	DNM1L	psi-mi:“MI:0914”(association)	0.350
EPB41L5	LIN7A	psi-mi:“MI:0914”(association)	0.350
TMEM69	ACOX3	psi-mi:“MI:0914”(association)	0.350
ARHGEF7	ACOX3	psi-mi:“MI:0914”(association)	0.350
PCDHGA9	UBA6	psi-mi:“MI:0914”(association)	0.350
PPP1CC	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PPP1CA	ADISSP	psi-mi:“MI:0915”(physical association)	0.000
PPP1CB	ADISSP	psi-mi:“MI:0915”(physical association)	0.000
PPP1R7	ADISSP	psi-mi:“MI:0915”(physical association)	0.000
FERMT2	ADISSP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Two-hybrid), RALYL (Two-hybrid), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), C20orf27 (Affinity Capture-MS)

ESM2 similar proteins: A6QLH6, B0KWT6, B1MTV8, B2GV38, B2KIK3, B5X9S9, B5XFI8, B7NZQ9, C1BGZ8, C9J798, O09172, O14908, O43374, O70422, P0CL18, P11441, P21126, P41214, P48507, P48508, P60027, Q0P5I8, Q2T9Y6, Q2TBN5, Q32LP0, Q3B7U9, Q58CR3, Q5R4T1, Q5R812, Q5RA63, Q5RB75, Q5RCR8, Q5ZMQ0, Q66H91, Q68FF6, Q7ZWB2, Q8BPA8, Q8IVD9, Q8R1T1, Q8WUX9

Diamond homologs: B5FX50, Q2KIM1, Q4KM45, Q68FA2, Q9D1K7, Q9GZN8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3024618	GRCh37/hg19 20p13-12.1(chr20:68351-16142323)x3	Pathogenic

SpliceAI

1094 predictions. Top by Δscore:

Variant	Effect	Δscore
20:3754154:CCGGT:C	acceptor_gain	1.0000
20:3754155:CGGT:C	acceptor_gain	1.0000
20:3754155:CGGTC:C	acceptor_gain	1.0000
20:3754156:GGT:G	acceptor_gain	1.0000
20:3754156:GGTC:G	acceptor_loss	1.0000
20:3754157:GT:G	acceptor_gain	1.0000
20:3754157:GTCT:G	acceptor_loss	1.0000
20:3754158:TCT:T	acceptor_loss	1.0000
20:3754159:C:CC	acceptor_gain	1.0000
20:3754160:T:C	acceptor_loss	1.0000
20:3754324:C:A	donor_gain	1.0000
20:3754388:CG:C	donor_gain	1.0000
20:3754516:TAAC:T	acceptor_gain	1.0000
20:3754525:C:T	acceptor_gain	1.0000
20:3755464:CGCA:C	donor_loss	1.0000
20:3755465:GCACC:G	donor_loss	1.0000
20:3755466:CACCT:C	donor_loss	1.0000
20:3758533:TA:T	donor_loss	1.0000
20:3758534:A:C	donor_loss	1.0000
20:3758535:CCT:C	donor_gain	1.0000
20:3758537:TTG:T	donor_gain	1.0000
20:3758538:TG:T	donor_gain	1.0000
20:3758561:T:A	donor_gain	1.0000
20:3758675:TTGC:T	acceptor_gain	1.0000
20:3758676:TGC:T	acceptor_gain	1.0000
20:3758676:TGCCT:T	acceptor_loss	1.0000
20:3758677:GC:G	acceptor_gain	1.0000
20:3758678:CC:C	acceptor_gain	1.0000
20:3758679:C:CA	acceptor_loss	1.0000
20:3758679:C:CC	acceptor_gain	1.0000

AlphaMissense

1148 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:3754140:G:T	P148H	1.000
20:3755599:G:C	F57L	1.000
20:3755599:G:T	F57L	1.000
20:3755600:A:G	F57S	1.000
20:3755601:A:G	F57L	1.000
20:3754122:A:T	V154D	0.999
20:3754141:G:A	P148S	0.999
20:3754141:G:T	P148T	0.999
20:3754146:C:T	G146D	0.999
20:3754402:A:T	V140D	0.999
20:3755580:A:G	Y64H	0.999
20:3755597:A:G	L58P	0.999
20:3755597:A:T	L58Q	0.999
20:3755600:A:C	F57C	0.999
20:3755601:A:C	F57V	0.999
20:3755603:C:T	G56D	0.999
20:3755604:C:G	G56R	0.999
20:3758540:A:T	V53D	0.999
20:3758576:A:T	V41D	0.999
20:3758602:A:C	F32L	0.999
20:3758602:A:T	F32L	0.999
20:3758604:A:G	F32L	0.999
20:3754064:A:C	F173L	0.998
20:3754064:A:T	F173L	0.998
20:3754066:A:G	F173L	0.998
20:3754134:A:G	L150P	0.998
20:3754134:A:T	L150Q	0.998
20:3754140:G:C	P148R	0.998
20:3754146:C:A	G146V	0.998
20:3754147:C:A	G146C	0.998

dbSNP variants (sampled 300 via entrez): RS1000211955 (20:3764666 C>T), RS1000267308 (20:3757914 G>A), RS1000416166 (20:3760083 C>T), RS1000752640 (20:3758747 C>G,T), RS1000812809 (20:3753114 C>T), RS1000814833 (20:3764388 A>G), RS1000851654 (20:3765383 G>C), RS1000917430 (20:3765112 G>C), RS1001224735 (20:3756647 G>A), RS1001416511 (20:3761383 T>C), RS1001601261 (20:3768008 G>A), RS1001716844 (20:3756472 G>A), RS1001879886 (20:3759195 C>G,T), RS1001907358 (20:3767029 C>A), RS1001968795 (20:3768175 C>T)

Disease associations

OMIM: gene MIM:620373 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002822_12	Survival in colon cancer	7.000000e-06
GCST003075_23	Cognitive decline rate in late mild cognitive impairment	6.000000e-07
GCST003075_62	Cognitive decline rate in late mild cognitive impairment	7.000000e-07
GCST004602_228	Mean corpuscular volume	3.000000e-12
GCST90002392_80	Mean corpuscular volume	6.000000e-38
GCST90002396_49	Mean reticulocyte volume	8.000000e-16
GCST90002397_445	Mean spheric corpuscular volume	7.000000e-39
GCST90002398_52	Neutrophil count	1.000000e-10
GCST90002403_310	Red blood cell count	8.000000e-09
GCST90002405_439	Reticulocyte count	6.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0000409	disease free survival
EFO:0007710	cognitive decline measurement
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0004305	erythrocyte count
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	3
cobaltous chloride	decreases expression	2
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
ICG 001	increases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Cadmium	increases abundance, increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Diazinon	increases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Selenium	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression, affects cotreatment	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Vitamin E	affects cotreatment, decreases expression, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2TA	Abcam HEK293T C20orf27 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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