C1QL3

Summary

C1QL3 (complement C1q like 3, HGNC:19359) is a protein-coding gene on chromosome 10p13, encoding Complement C1q-like protein 3 (Q5VWW1). May regulate the number of excitatory synapses that are formed on hippocampus neurons.

Predicted to enable identical protein binding activity. Predicted to be involved in neurotransmitter receptor localization to postsynaptic specialization membrane and postsynaptic density assembly. Predicted to act upstream of or within regulation of synapse organization. Predicted to be located in extracellular region. Predicted to be part of collagen trimer. Predicted to be active in glutamatergic synapse; hippocampal mossy fiber to CA3 synapse; and synaptic cleft.

Source: NCBI Gene 389941 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_001010908

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19359
Approved symbol	C1QL3
Name	complement C1q like 3
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	K100, C1ql, C1QTNF13, CTRP13
Ensembl gene	ENSG00000165985
Ensembl biotype	protein_coding
OMIM	615227
Entrez	389941

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000298943, ENST00000718439

RefSeq mRNA: 1 — MANE Select: NM_001010908 NM_001010908

CCDS: CCDS31156

Canonical transcript exons

ENST00000298943 — 2 exons

Exon	Start	End
ENSE00001337137	16520478	16521879
ENSE00001387459	16513734	16514707

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 90.26.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.1496 / max 235.4550, expressed in 134 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108455	0.8405	73
108454	0.7130	65
108449	0.3901	104
108451	0.1078	48
108450	0.0803	40
108452	0.0180	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	90.26	gold quality
prefrontal cortex	UBERON:0000451	86.00	gold quality
frontal cortex	UBERON:0001870	81.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.17	gold quality
anterior cingulate cortex	UBERON:0009835	77.75	gold quality
cerebral cortex	UBERON:0000956	77.24	gold quality
right frontal lobe	UBERON:0002810	74.13	gold quality
primary visual cortex	UBERON:0002436	70.88	gold quality
cerebellum	UBERON:0002037	69.45	gold quality
cerebellar cortex	UBERON:0002129	69.17	gold quality
cerebellar hemisphere	UBERON:0002245	68.98	gold quality
cortical plate	UBERON:0005343	67.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.61	gold quality
temporal lobe	UBERON:0001871	65.78	gold quality
Ammon’s horn	UBERON:0001954	65.58	gold quality
amygdala	UBERON:0001876	65.29	gold quality
duodenum	UBERON:0002114	64.35	gold quality
calcaneal tendon	UBERON:0003701	63.93	gold quality
monocyte	CL:0000576	62.62	gold quality
leukocyte	CL:0000738	62.26	gold quality
brain	UBERON:0000955	61.92	gold quality
hypothalamus	UBERON:0001898	61.28	gold quality
islet of Langerhans	UBERON:0000006	60.98	gold quality
skeletal muscle tissue	UBERON:0001134	59.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	59.16	gold quality
adult mammalian kidney	UBERON:0000082	58.74	gold quality
muscle tissue	UBERON:0002385	57.84	gold quality
corpus callosum	UBERON:0002336	57.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting C1QL3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-466	99.67	70.85	2863

Literature-anchored findings (GeneRIF, showing 11)

• CTRP13 reduces glucose output in hepatocytes by inhibiting the mRNA expression of gluconeogenic enzymes, glucose-6-phosphatase and the cytosolic form of phosphoenolpyruvate carboxykinase. (PMID:21378161)
• decreased levels of CTRP3 and especially CTRP13 were associated with increased risk of T2DM and CAD (PMID:28033351)
• CTRP13 is a novel adipokine that is down-regulated in the serum of type 2 diabetics. (PMID:28182339)
• findings define CTRP13 as a novel approach for preventing atherosclerotic plaque formation via modulation of lipid uptake and foam-cell migration (PMID:30222079)
• BAI3 mediates the inhibitory effects of C1ql3 on insulin secretion from pancreatic beta-cells. (PMID:30228187)
• Study results indicated that decreased adiponectin, CTRP12, and CTRP13 levels, regardless of obesity, could independently predict polycystic ovarian syndrome (PCOS). This finding suggested a novel link between adipokines and PCOS. (PMID:30540803)
• CTRP13 preserves endothelial function in diabetic mice by regulating GCH1/BH4 axis-dependent eNOS coupling, suggesting the therapeutic potential of CTRP13 against diabetic vasculopathy. (PMID:31676569)
• Low Complement C1q/TNF-related Protein-13 Levels are Associated with Childhood Obesity But not Binge Eating Disorder (PMID:35014243)
• CTRP13 ablation improves systemic glucose and lipid metabolism. (PMID:37844630)
• CTRP13 alleviates palmitic acid-induced inflammation, oxidative stress, apoptosis and endothelial cell dysfunction in HUVECs. (PMID:37976900)
• CTRP13 Mitigates Endothelial Cell Ferroptosis via the AMPK/KLF4 Pathway: Implications for Atherosclerosis Protection. (PMID:38273650)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1ql3a	ENSDARG00000010350
danio_rerio	c1ql3b	ENSDARG00000036483
mus_musculus	C1ql3	ENSMUSG00000049630
rattus_norvegicus	C1ql3	ENSRNOG00000017459

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), 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-like protein 3 — Q5VWW1 (reviewed: Q5VWW1)

Alternative names: C1q and tumor necrosis factor-related protein 13

All UniProt accessions (2): A0A3B0J0F3, Q5VWW1

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the number of excitatory synapses that are formed on hippocampus neurons. Has no effect on inhibitory synapses. Plays a role in glucose homeostasis. Via AMPK signaling pathway, stimulates glucose uptake in adipocytes, myotubes and hepatocytes and enhances insulin-stimulated glucose uptake. In a hepatoma cell line, reduces the expression of gluconeogenic enzymes G6PC1 and PCK1 and hence decreases de novo glucose production.

Subunit / interactions. Forms homooligomers. Interacts with ADGRB3. Interacts with C1QL2 and C1QL4, when proteins are coexpressed; this interaction does not occur after secretion.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in adipose tissue, with expression levels at least 2 orders of magnitude higher than in other tissues, including brain and kidney.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5VWW1-1	1	yes
Q5VWW1-2	2
Q5VWW1-3	3

RefSeq proteins (1): NP_001010908* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR050822	Cerebellin_Synaptic_Org	Family

Pfam: PF00386, PF01391

UniProt features (8 total): domain 2, splice variant 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VWW1-F1	80.16	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, GOCC_COLLAGEN_TRIMER, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELL_CELL_SIGNALING, chr10p13, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_PROTEIN_LOCALIZATION_TO_SYNAPSE

GO Biological Process (3): regulation of synapse organization (GO:0050807), postsynaptic density assembly (GO:0097107), neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): collagen trimer (GO:0005581), synaptic cleft (GO:0043083), hippocampal mossy fiber to CA3 synapse (GO:0098686), glutamatergic synapse (GO:0098978), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
postsynaptic density organization	1
postsynaptic specialization assembly	1
excitatory synapse assembly	1
protein-containing complex localization	1
receptor localization to synapse	1
regulation of postsynaptic membrane neurotransmitter receptor levels	1
protein localization to postsynaptic specialization membrane	1
protein binding	1
binding	1
protein-containing complex	1
extracellular region	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1
synapse	1

Protein interactions and networks

STRING

986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QL3	GRIK4	Q16099	785
C1QL3	ADGRB3	O60242	768
C1QL3	GRIK2	Q13002	665
C1QL3	C1QTNF12	Q5T7M4	584
C1QL3	NRXN1	Q9ULB1	567
C1QL3	NRXN2	Q9P2S2	546
C1QL3	C1QTNF1	Q9BXJ1	466
C1QL3	C1QTNF8	P60827	465
C1QL3	KCNS1	Q96KK3	459
C1QL3	GRIA1	P42261	451
C1QL3	C1QL2	Q7Z5L3	447
C1QL3	C1QTNF9	P0C862	446
C1QL3	ERFE	Q4G0M1	435
C1QL3	ST6GALNAC5	Q9BVH7	396
C1QL3	CDH9	Q9ULB4	395

IntAct

2 interactions, top by confidence:

A	B	Type	Score
C1QL3	TSC22D2	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): C1QL3 (Affinity Capture-MS), BAI3 (Reconstituted Complex), C1QL3 (Reconstituted Complex), TSC22D2 (Affinity Capture-MS), HBB (Affinity Capture-MS), HBA2 (Affinity Capture-MS), TSC22D3 (Affinity Capture-MS), NRBP1 (Affinity Capture-MS)

ESM2 similar proteins: A2A5I3, A5D8T8, B2RY83, D3ZE85, O19116, O43692, O75882, P16562, P24786, P52848, P78539, P97401, Q01973, Q02353, Q08DW9, Q16288, Q3KPV7, Q3UHN9, Q4R766, Q58D84, Q5IFJ9, Q5IS37, Q5IS82, Q5RF67, Q5VV63, Q5VWW1, Q5ZIN0, Q62632, Q63769, Q6A051, Q6AYT7, Q6UXF7, Q6VNS1, Q7T141, Q80ZF8, Q8BS03, Q8C4U3, Q8N2K0, Q8N474, Q8NCF0

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

119 predictions. Top by Δscore:

Variant	Effect	Δscore
10:16514707:CCTA:C	acceptor_gain	1.0000
10:16520473:CTCA:C	donor_loss	1.0000
10:16520474:TCA:T	donor_loss	1.0000
10:16520475:CA:C	donor_loss	1.0000
10:16514703:CGCAC:C	acceptor_gain	0.9900
10:16514705:CAC:C	acceptor_gain	0.9900
10:16514707:CC:C	acceptor_loss	0.9900
10:16514708:C:CA	acceptor_loss	0.9900
10:16514709:T:C	acceptor_loss	0.9900
10:16514710:A:C	acceptor_gain	0.9900
10:16514712:G:C	acceptor_gain	0.9900
10:16520477:CCTGG:C	donor_gain	0.9900
10:16514710:A:AC	acceptor_gain	0.9800
10:16514712:G:GC	acceptor_gain	0.9800
10:16514718:C:CT	acceptor_gain	0.9800
10:16520476:A:AC	donor_gain	0.9800
10:16520477:C:CC	donor_gain	0.9800
10:16514704:GCAC:G	acceptor_gain	0.9700
10:16514705:CACC:C	acceptor_gain	0.9700
10:16514706:AC:A	acceptor_gain	0.9700
10:16514708:C:CC	acceptor_gain	0.9700
10:16514719:A:T	acceptor_gain	0.9700
10:16520472:GCTCA:G	donor_loss	0.9600
10:16520477:CCT:C	donor_gain	0.9500
10:16520477:CCTG:C	donor_gain	0.9400
10:16520476:AC:A	donor_gain	0.9300
10:16520477:CC:C	donor_gain	0.9300
10:16520583:G:A	donor_gain	0.8800
10:16515918:A:AC	donor_gain	0.8700
10:16514706:ACCT:A	acceptor_gain	0.8500

AlphaMissense

1659 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:16514550:C:T	G249E	1.000
10:16514551:C:G	G249R	1.000
10:16514551:C:T	G249R	1.000
10:16514561:G:C	S245R	1.000
10:16514561:G:T	S245R	1.000
10:16514563:T:G	S245R	1.000
10:16514565:T:C	Y244C	1.000
10:16514566:A:G	Y244H	1.000
10:16514570:G:C	N242K	1.000
10:16514570:G:T	N242K	1.000
10:16514583:C:T	G238E	1.000
10:16514634:A:C	L221W	1.000
10:16514640:A:G	L219P	1.000
10:16514648:A:C	S216R	1.000
10:16514648:A:T	S216R	1.000
10:16514650:T:G	S216R	1.000
10:16514651:G:C	N215K	1.000
10:16514651:G:T	N215K	1.000
10:16514654:A:C	S214R	1.000
10:16514654:A:T	S214R	1.000
10:16514656:T:G	S214R	1.000
10:16514658:G:T	A213D	1.000
10:16514664:T:A	D211V	1.000
10:16514665:C:G	D211H	1.000
10:16514668:A:G	Y210H	1.000
10:16514682:T:A	D205V	1.000
10:16514682:T:G	D205A	1.000
10:16514683:C:G	D205H	1.000
10:16514684:T:A	Q204H	1.000
10:16514684:T:G	Q204H	1.000

dbSNP variants (sampled 300 via entrez): RS1000060872 (10:16516467 A>G), RS1000167046 (10:16521749 G>A,C,T), RS1000545642 (10:16518082 A>T), RS1000578398 (10:16517838 C>G,T), RS1001263749 (10:16515359 T>A), RS1001365657 (10:16521347 G>A), RS1001546136 (10:16516844 G>A), RS1001577368 (10:16516561 T>G), RS1001579959 (10:16523363 A>T), RS1002552138 (10:16515502 G>T), RS1002574577 (10:16521961 T>A), RS1002774331 (10:16521490 C>G), RS1002959829 (10:16514027 G>A), RS1003033038 (10:16520032 C>A,T), RS1003065709 (10:16520279 G>C)

Disease associations

OMIM: gene MIM:615227 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Cadmium	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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