C1QTNF2

Summary

C1QTNF2 (C1q and TNF related 2, HGNC:14325) is a protein-coding gene on chromosome 5q33.3, encoding Complement C1q tumor necrosis factor-related protein 2 (Q9BXJ5). Involved in the regulation of lipid metabolism in adipose tissue and liver.

Predicted to enable identical protein binding activity and signaling receptor binding activity. Predicted to be involved in regulation of lipid metabolic process. Predicted to act upstream of or within positive regulation of D-glucose import; positive regulation of MAPK cascade; and positive regulation of small molecule metabolic process. Predicted to be located in extracellular space. Predicted to be part of protein-containing complex.

Source: NCBI Gene 114898 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 70 total — 1 likely-pathogenic
• MANE Select transcript: NM_031908

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14325
Approved symbol	C1QTNF2
Name	C1q and TNF related 2
Location	5q33.3
Locus type	gene with protein product
Status	Approved
Aliases	CTRP2
Ensembl gene	ENSG00000145861
Ensembl biotype	protein_coding
OMIM	618647
Entrez	114898

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000393975, ENST00000652664, ENST00000891629, ENST00000950991

RefSeq mRNA: 2 — MANE Select: NM_031908 NM_001366504, NM_031908

CCDS: CCDS4351

Canonical transcript exons

ENST00000652664 — 3 exons

Exon	Start	End
ENSE00001210106	160347754	160349781
ENSE00003846241	160370512	160370626
ENSE00003846306	160354768	160355020

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 82.82.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4358 / max 44.2207, expressed in 512 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64627	0.9923	410
64626	0.4435	216

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ascending aorta	UBERON:0001496	82.82	gold quality
thoracic aorta	UBERON:0001515	82.80	gold quality
descending thoracic aorta	UBERON:0002345	82.45	gold quality
right coronary artery	UBERON:0001625	81.48	gold quality
aorta	UBERON:0000947	80.70	gold quality
tendon of biceps brachii	UBERON:0008188	80.39	gold quality
popliteal artery	UBERON:0002250	79.19	gold quality
tibial artery	UBERON:0007610	79.18	gold quality
saphenous vein	UBERON:0007318	78.07	gold quality
left coronary artery	UBERON:0001626	77.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.02	silver quality
coronary artery	UBERON:0001621	76.91	gold quality
urethra	UBERON:0000057	75.13	gold quality
calcaneal tendon	UBERON:0003701	73.33	gold quality
synovial joint	UBERON:0002217	73.14	gold quality
tendon	UBERON:0000043	73.07	gold quality
apex of heart	UBERON:0002098	71.41	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.84	gold quality
layer of synovial tissue	UBERON:0007616	70.34	gold quality
skin of hip	UBERON:0001554	70.02	gold quality
endocervix	UBERON:0000458	69.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	69.56	gold quality
lower esophagus	UBERON:0013473	69.46	gold quality
left uterine tube	UBERON:0001303	69.39	gold quality
mucosa of stomach	UBERON:0001199	69.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.01	gold quality
stromal cell of endometrium	CL:0002255	68.24	gold quality
right atrium auricular region	UBERON:0006631	68.18	gold quality
ectocervix	UBERON:0012249	68.05	gold quality
tibial nerve	UBERON:0001323	67.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	28.69
E-ANND-3	no	2.80

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• CTRP2 regulates lipid metabolism in adipose tissue and liver. (PMID:31439668)
• Serum C1q/TNF-Related Protein-2 (CTRP2) Levels are Associated with Coronary Artery Disease. (PMID:32147289)
• Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training. (PMID:33874963)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1qtnf2	ENSDARG00000059944
mus_musculus	C1qtnf2	ENSMUSG00000046491
rattus_norvegicus	C1qtnf2	ENSRNOG00000003870

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), C1QTNF4 (ENSG00000172247), C1QB (ENSG00000173369), C1QA (ENSG00000173372), C1QTNF1 (ENSG00000173918), ADIPOQ (ENSG00000181092), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Complement C1q tumor necrosis factor-related protein 2 — Q9BXJ5 (reviewed: Q9BXJ5)

All UniProt accessions (3): A0A3B0INC0, A0A499FIM1, Q9BXJ5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the regulation of lipid metabolism in adipose tissue and liver.

Subunit / interactions. May interact with ERFE.

Subcellular location. Secreted.

Tissue specificity. Expressed in adipose tissue.

RefSeq proteins (2): NP_001353433, NP_114114* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR050392	Collagen/C1q_domain	Family

Pfam: PF00386, PF01391

UniProt features (9 total): compositionally biased region 4, domain 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXJ5-F1	72.73	0.44

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOCC_COLLAGEN_TRIMER, GCANCTGNY_MYOD_Q6, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, SEKI_INFLAMMATORY_RESPONSE_LPS_DN, CHICAS_RB1_TARGETS_GROWING, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, TERF1_TARGET_GENES, ZNF513_TARGET_GENES, MIR548F_5P, MIR548AJ_5P_MIR548G_5P_MIR548X_5P, MIR3179, MIR6758_3P

GO Biological Process (1): regulation of lipid metabolic process (GO:0019216)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), collagen trimer (GO:0005581)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	1
regulation of primary metabolic process	1
binding	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

848 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QTNF2	ADIPOR1	Q96A54	638
C1QTNF2	CD93	Q9NPY3	547
C1QTNF2	GPT	P24298	507
C1QTNF2	TMEM217B	A0A494BZU4	505
C1QTNF2	TMEM217	Q8N7C4	475
C1QTNF2	C1QTNF12	Q5T7M4	446
C1QTNF2	CDH13	P55290	438
C1QTNF2	CAMKK2	Q96RR4	425
C1QTNF2	LPXN	O60711	414
C1QTNF2	ERFE	Q4G0M1	393
C1QTNF2	SELE	P16111	381
C1QTNF2	TIMP1	P01033	356
C1QTNF2	VCAM1	P19320	352
C1QTNF2	DEFB116	Q30KQ4	348
C1QTNF2	NICOL1	Q5BLP8	335

IntAct

107 interactions, top by confidence:

A	B	Type	Score
C1QTNF2	NCALD	psi-mi:“MI:0915”(physical association)	0.750
NCALD	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.750
HPCAL1	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.720
C1QTNF2	KLHL12	psi-mi:“MI:0915”(physical association)	0.720
C1QTNF2	HPCAL1	psi-mi:“MI:0915”(physical association)	0.720
KLHL12	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.720
C1QTNF2	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560
C1QTNF2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
ANKRD11	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560
KCNIP3	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560
USP20	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560
P4HA3	C1QTNF2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (106): C1QTNF2 (Two-hybrid), C1QTNF2 (Two-hybrid), C1QTNF2 (Two-hybrid), C1QTNF2 (Two-hybrid), C1QTNF2 (Two-hybrid), APPBP2 (Affinity Capture-MS), MCMBP (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COL2A1 (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), DMXL2 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), MCM5 (Affinity Capture-MS), SELO (Affinity Capture-MS)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WGB1, A8WR59, B2RNN3, B7Z0K8, C7DZK3, O35167, O35348, O76368, O88207, P0C862, P12107, P13942, P20908, P20909, P23805, P25067, P25318, P25940, P42916, P83371, P98085, Q03637, Q07092, Q07563, Q0II24, Q0VF58, Q17RW2, Q30D77, Q32S24, Q3MI99, Q4ZJM7, Q4ZJN1, Q60467, Q61245, Q64739, Q6UXH8

Diamond homologs: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, O75973, O88992, P02745, P02746, P08125, P0C862, P14106, P14282, P23206, P25067, P25318, P27658, P31720, P31721, P83371, P98085, P98086, Q00780, Q02105, Q03692, Q05306, Q05A80, Q06575, Q06576, Q06577, Q0II24, Q15848, Q2KIU3, Q2KIX7, Q3Y5Z3, Q4ZJM7, Q4ZJM9, Q4ZJN1, Q5E9E3, Q5FVH0, Q5RJ80

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of signal transduction	6	47.2×	8e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	62
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
814759	GRCh37/hg19 5q33.3-34(chr5:159714197-161313217)x1	Likely pathogenic

SpliceAI

672 predictions. Top by Δscore:

Variant	Effect	Δscore
5:160370507:CTCA:C	donor_loss	1.0000
5:160370510:A:AC	donor_gain	1.0000
5:160370510:AC:A	donor_gain	1.0000
5:160370511:C:CC	donor_gain	1.0000
5:160370511:C:CG	donor_loss	1.0000
5:160370511:CC:C	donor_gain	1.0000
5:160370511:CCCT:C	donor_gain	1.0000
5:160354762:TCTTA:T	donor_loss	0.9900
5:160354763:CTTA:C	donor_loss	0.9900
5:160354764:TTACC:T	donor_loss	0.9900
5:160354765:TACC:T	donor_loss	0.9900
5:160354767:C:CA	donor_loss	0.9900
5:160370510:ACC:A	donor_gain	0.9900
5:160370511:CCC:C	donor_gain	0.9900
5:160354766:ACCTT:A	donor_gain	0.9800
5:160354767:CCTTC:C	donor_gain	0.9800
5:160354770:T:A	donor_gain	0.9800
5:160370510:ACCCT:A	donor_gain	0.9800
5:160370511:CCCTC:C	donor_gain	0.9800
5:160354761:CTCTT:C	donor_loss	0.9700
5:160370506:ACTC:A	donor_loss	0.9600
5:160354755:ATAGG:A	donor_gain	0.9500
5:160349781:CCTGG:C	acceptor_loss	0.9400
5:160349782:C:CA	acceptor_loss	0.9400
5:160349783:T:A	acceptor_loss	0.9400
5:160354767:CCTT:C	donor_gain	0.9300
5:160349784:G:C	acceptor_loss	0.9200
5:160349791:A:T	acceptor_loss	0.9200
5:160370504:ACACT:A	donor_loss	0.9100
5:160370505:CACTC:C	donor_loss	0.9100

AlphaMissense

1840 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:160349217:A:G	F270S	0.999
5:160349222:G:C	S268R	0.999
5:160349222:G:T	S268R	0.999
5:160349224:T:G	S268R	0.999
5:160349280:A:G	L249P	0.999
5:160349391:A:G	L212P	0.999
5:160349403:A:G	L208P	0.999
5:160349436:A:G	F197S	0.999
5:160349571:A:G	F152S	0.999
5:160349277:T:G	Q250P	0.998
5:160349326:A:G	S234P	0.998
5:160349431:A:C	Y199D	0.998
5:160349443:A:C	Y195D	0.998
5:160349459:G:C	C189W	0.998
5:160349472:C:A	G185V	0.998
5:160349519:A:C	F169L	0.998
5:160349519:A:T	F169L	0.998
5:160349521:A:G	F169L	0.998
5:160349570:G:C	F152L	0.998
5:160349570:G:T	F152L	0.998
5:160349571:A:C	F152C	0.998
5:160349572:A:G	F152L	0.998
5:160349211:C:T	G272D	0.997
5:160349286:A:T	V247D	0.997
5:160349320:A:G	S236P	0.997
5:160349357:A:C	F223L	0.997
5:160349357:A:T	F223L	0.997
5:160349359:A:G	F223L	0.997
5:160349449:C:A	G193W	0.997
5:160349460:C:T	C189Y	0.997

dbSNP variants (sampled 300 via entrez): RS1000159859 (5:160361491 A>G), RS1000228363 (5:160351974 G>A,T), RS1000247378 (5:160358140 G>A), RS1000536667 (5:160350742 C>T), RS1000545708 (5:160357262 T>C), RS1000576943 (5:160356981 G>A,T), RS1000601586 (5:160352237 G>A), RS1000668431 (5:160365588 C>CAAAGA), RS1000773410 (5:160371322 C>T), RS1000844184 (5:160364138 C>T), RS1000944313 (5:160368392 T>C), RS1000970002 (5:160348089 C>T), RS1000976803 (5:160368153 G>C), RS1001189818 (5:160352325 T>G), RS1001201705 (5:160353697 C>A)

Disease associations

OMIM: gene MIM:618647 | 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
GCST001991_1	Weight loss (gastric bypass surgery)	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005245	body weight loss

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	increases expression, increases methylation	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
trichostatin A	increases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
1-nitropyrene	decreases expression	1
pentanal	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Estradiol	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Aflatoxin B1	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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