C1QL2

Summary

C1QL2 (complement C1q like 2, HGNC:24181) is a protein-coding gene on chromosome 2q14.2, encoding Complement C1q-like protein 2 (Q7Z5L3). 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; postsynaptic density assembly; and regulation of synapse maturation. Predicted to be located in extracellular region. Predicted to be part of collagen trimer. Predicted to be active in cerebellar climbing fiber to Purkinje cell synapse; hippocampal mossy fiber to CA3 synapse; and synaptic cleft.

Source: NCBI Gene 165257 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 46 total — 4 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_182528

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24181
Approved symbol	C1QL2
Name	complement C1q like 2
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Aliases	CTRP10, C1QTNF10
Ensembl gene	ENSG00000144119
Ensembl biotype	protein_coding
OMIM	614330
Entrez	165257

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000272520, ENST00000850649

RefSeq mRNA: 1 — MANE Select: NM_182528 NM_182528

CCDS: CCDS42737

Canonical transcript exons

ENST00000272520 — 2 exons

Exon	Start	End
ENSE00000963674	119157586	119158751
ENSE00000963675	119156243	119156981

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 86.01.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4760 / max 49.5731, expressed in 133 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30404	0.2769	96
30408	0.0577	31
30406	0.0459	21
30407	0.0384	19
30403	0.0383	26
30405	0.0125	2
30409	0.0062	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
temporal lobe	UBERON:0001871	86.01	gold quality
amygdala	UBERON:0001876	85.99	gold quality
Ammon’s horn	UBERON:0001954	85.24	gold quality
superior frontal gyrus	UBERON:0002661	81.35	gold quality
anterior cingulate cortex	UBERON:0009835	81.34	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.54	gold quality
cerebral cortex	UBERON:0000956	79.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.63	gold quality
right frontal lobe	UBERON:0002810	79.58	gold quality
hypothalamus	UBERON:0001898	79.38	gold quality
nucleus accumbens	UBERON:0001882	78.47	gold quality
frontal cortex	UBERON:0001870	78.26	gold quality
primary visual cortex	UBERON:0002436	77.40	gold quality
prefrontal cortex	UBERON:0000451	77.09	gold quality
putamen	UBERON:0001874	74.58	gold quality
caudate nucleus	UBERON:0001873	74.44	gold quality
substantia nigra	UBERON:0002038	74.25	gold quality
brain	UBERON:0000955	72.10	gold quality
ventricular zone	UBERON:0003053	67.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.37	gold quality
ganglionic eminence	UBERON:0004023	59.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	57.43	gold quality
cerebellum	UBERON:0002037	56.87	gold quality
cerebellar cortex	UBERON:0002129	56.73	gold quality
cerebellar hemisphere	UBERON:0002245	56.61	gold quality
skin of leg	UBERON:0001511	46.00	gold quality
zone of skin	UBERON:0000014	43.48	gold quality
adenohypophysis	UBERON:0002196	42.45	gold quality
lymph node	UBERON:0000029	41.87	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	5.64
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting C1QL2, 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-6748-5P	100.00	65.81	1057
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-3677-5P	93.16	64.62	393

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1ql2	ENSDARG00000015592
mus_musculus	C1ql2	ENSMUSG00000036907
rattus_norvegicus	C1ql2	ENSRNOG00000046863

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), 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-like protein 2 — Q7Z5L3 (reviewed: Q7Z5L3)

Alternative names: C1q and tumor necrosis factor-related protein 10

All UniProt accessions (2): Q7Z5L3, A0A3B0IND4

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.

Subunit / interactions. Forms homotrimers which can further assemble to form higher-order oligomeric complexes. Interacts with ADGRB3. May interact with ERFE. Forms heterooligomers with C1QL3 and C1QL4, when proteins are coexpressed; this interaction does not occur after secretion.

Subcellular location. Secreted.

RefSeq proteins (1): NP_872334* (*=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, sequence conflict 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-Q7Z5L3-F1	75.90	0.45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): PAX4_01, GOBP_SYNAPSE_ASSEMBLY, GOCC_COLLAGEN_TRIMER, GOBP_CELLULAR_COMPONENT_MAINTENANCE, AP2_Q3, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, AAAGACA_MIR511, 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 maturation (GO:0090128), 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 (7): collagen trimer (GO:0005581), synaptic cleft (GO:0043083), hippocampal mossy fiber to CA3 synapse (GO:0098686), cerebellar climbing fiber to Purkinje cell synapse (GO:0150053), extracellular region (GO:0005576), protein-containing complex (GO:0032991), glutamatergic synapse (GO:0098978)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of developmental process	1
regulation of synapse organization	1
synapse maturation	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
asymmetric, glutamatergic, excitatory synapse	1
cellular_component	1
synapse	1

Protein interactions and networks

STRING

1430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QL2	GRIK4	Q16099	688
C1QL2	GRIK2	Q13002	648
C1QL2	KARS1	Q15046	574
C1QL2	NRXN3	Q9Y4C0	514
C1QL2	NRXN2	Q9P2S2	503
C1QL2	ADGRB3	O60242	502
C1QL2	NRXN1	Q9ULB1	493
C1QL2	C1QTNF8	P60827	491
C1QL2	DPY19L4	Q7Z388	491
C1QL2	TMEM9B	Q9NQ34	463
C1QL2	CCNQ	Q8N1B3	460
C1QL2	NOC4L	Q9BVI4	456
C1QL2	C1QTNF1	Q9BXJ1	455
C1QL2	VWA7	Q9Y334	453
C1QL2	C1QL3	Q5VWW1	447

IntAct

0 interactions, top by confidence:

BioGRID (1): C1QL2 (Affinity Capture-MS)

ESM2 similar proteins: A5PKD9, B1AXV0, D1LYT2, D3Z7P3, D3ZB51, D3ZE85, D3ZTX0, E9PZ19, G3MWR8, O75973, O88508, O88992, O94925, P13264, P27467, P47870, P56704, P63137, Q00961, Q01098, Q08DW9, Q12841, Q14957, Q1LZ53, Q2LMP1, Q4R766, Q4W5Z4, Q4ZJM9, Q58D84, Q5R9Y1, Q5VWW1, Q5ZIN0, Q62356, Q62632, Q6AYT7, Q6AZB0, Q6UXG2, Q76LW2, Q7RTP6, Q7Z5L3

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

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	38
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
155658	GRCh38/hg38 2q14.2-14.3(chr2:118687829-121621814)x1	Pathogenic
1809385	GRCh37/hg19 2q14.1-14.3(chr2:116761476-123897262)x1	Pathogenic
442443	GRCh37/hg19 2q14.1-14.3(chr2:116754600-123897370)x1	Pathogenic
4755368	GRCh38/hg38 2q14.1-14.3(chr2:115987911-123142972)x1	Pathogenic
3062627	GRCh37/hg19 2q14.1-14.3(chr2:116646793-126388760)x1	Likely pathogenic

SpliceAI

366 predictions. Top by Δscore:

Variant	Effect	Δscore
2:119156977:CGGAC:C	acceptor_gain	1.0000
2:119156982:C:CC	acceptor_gain	0.9900
2:119157581:CTGA:C	donor_loss	0.9900
2:119157582:TGA:T	donor_loss	0.9900
2:119157583:GAC:G	donor_loss	0.9900
2:119157584:AC:A	donor_loss	0.9900
2:119157588:G:A	donor_gain	0.9900
2:119156978:GGAC:G	acceptor_gain	0.9800
2:119156979:GAC:G	acceptor_gain	0.9800
2:119156980:AC:A	acceptor_gain	0.9800
2:119156981:CC:C	acceptor_gain	0.9800
2:119156989:C:CT	acceptor_gain	0.9800
2:119157062:ACGGG:A	donor_gain	0.9600
2:119157063:CGGGC:C	donor_gain	0.9600
2:119157097:C:CA	donor_gain	0.9600
2:119157584:ACCTG:A	donor_gain	0.9600
2:119157585:CCTGC:C	donor_gain	0.9600
2:119157062:A:AC	donor_gain	0.9300
2:119157063:C:CC	donor_gain	0.9300
2:119157411:C:A	donor_gain	0.9300
2:119157584:A:AC	donor_gain	0.9300
2:119157585:C:CC	donor_gain	0.9300
2:119156990:A:T	acceptor_gain	0.9200
2:119157452:TGTGG:T	donor_gain	0.9200
2:119157585:CCTG:C	donor_gain	0.9000
2:119157410:T:TA	donor_gain	0.8900
2:119157579:CACT:C	donor_loss	0.8900
2:119157121:T:A	donor_gain	0.8800
2:119157387:AAGGC:A	donor_gain	0.8800
2:119156994:G:T	acceptor_gain	0.8600

AlphaMissense

1856 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:119156820:A:C	F282L	1.000
2:119156820:A:T	F282L	1.000
2:119156822:A:G	F282L	1.000
2:119156824:C:T	G281D	1.000
2:119156825:C:G	G281R	1.000
2:119156828:A:G	S280P	1.000
2:119156829:G:C	F279L	1.000
2:119156829:G:T	F279L	1.000
2:119156830:A:C	F279C	1.000
2:119156830:A:G	F279S	1.000
2:119156831:A:G	F279L	1.000
2:119156833:G:T	T278K	1.000
2:119156835:G:C	S277R	1.000
2:119156835:G:T	S277R	1.000
2:119156837:T:G	S277R	1.000
2:119156839:T:C	Y276C	1.000
2:119156839:T:G	Y276S	1.000
2:119156840:A:G	Y276H	1.000
2:119156841:C:A	K275N	1.000
2:119156841:C:G	K275N	1.000
2:119156843:T:C	K275E	1.000
2:119156844:G:C	N274K	1.000
2:119156844:G:T	N274K	1.000
2:119156855:C:G	G271R	1.000
2:119156857:C:T	G270E	1.000
2:119156858:C:G	G270R	1.000
2:119156858:C:T	G270R	1.000
2:119156861:G:C	H269D	1.000
2:119156863:G:T	A268D	1.000
2:119156869:C:A	G266V	1.000

dbSNP variants (sampled 300 via entrez): RS1000183501 (2:119160012 G>C), RS1001447505 (2:119157588 G>A,C), RS1002465342 (2:119156344 G>A), RS1003084855 (2:119160228 T>G), RS1003423066 (2:119157437 G>A), RS1003790840 (2:119156526 C>G,T), RS1005438226 (2:119155758 T>C), RS1005797311 (2:119158781 C>G,T), RS1006150790 (2:119160179 C>A,G,T), RS1006379358 (2:119158561 CGT>C), RS1006782226 (2:119158381 G>A), RS1007036535 (2:119158181 C>T), RS1007373450 (2:119159523 C>T), RS1007567657 (2:119160611 AG>A,AGG), RS1007841805 (2:119159624 G>A,C)

Disease associations

OMIM: gene MIM:614330 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002688_10	Very long-chain saturated fatty acid levels (fatty acid 22:0)	8.000000e-06
GCST009391_286	Metabolite levels	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0010424	triacylglycerol 54:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, decreases reaction	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Copper	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Malathion	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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