C1QL1

Summary

C1QL1 (complement C1q like 1, HGNC:24182) is a protein-coding gene on chromosome 17q21.31, encoding C1q-related factor (O75973). May regulate the number of excitatory synapses that are formed on hippocampus neurons.

Predicted to enable signaling receptor binding activity. Predicted to be involved in locomotory behavior. Predicted to act upstream of or within maintenance of synapse structure; motor learning; and neuron remodeling. Predicted to be located in several cellular components, including climbing fiber; extracellular region; and presynapse. Predicted to be part of collagen trimer. Predicted to be active in cerebellar climbing fiber to Purkinje cell synapse and synaptic cleft.

Source: NCBI Gene 10882 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 44 total — 1 pathogenic
• MANE Select transcript: NM_006688

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24182
Approved symbol	C1QL1
Name	complement C1q like 1
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	CRF, C1QRF, C1QTNF14, CTRP14
Ensembl gene	ENSG00000131094
Ensembl biotype	protein_coding
OMIM	611586
Entrez	10882

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000253407, ENST00000718438

RefSeq mRNA: 1 — MANE Select: NM_006688 NM_006688

CCDS: CCDS11492

Canonical transcript exons

ENST00000253407 — 2 exons

Exon	Start	End
ENSE00000854296	44959693	44960367
ENSE00000854297	44967452	44968303

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 93.70.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6959 / max 287.6817, expressed in 693 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166484	3.0294	639
166483	0.3753	187
166485	0.2912	153

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	93.70	gold quality
middle frontal gyrus	UBERON:0002702	92.66	silver quality
Brodmann (1909) area 10	UBERON:0013541	91.73	silver quality
amygdala	UBERON:0001876	89.63	gold quality
cingulate cortex	UBERON:0003027	88.80	gold quality
anterior cingulate cortex	UBERON:0009835	88.80	gold quality
endometrium epithelium	UBERON:0004811	88.73	gold quality
hypothalamus	UBERON:0001898	87.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.97	gold quality
spinal cord	UBERON:0002240	86.61	gold quality
right frontal lobe	UBERON:0002810	84.30	gold quality
type B pancreatic cell	CL:0000169	84.14	silver quality
temporal lobe	UBERON:0001871	83.97	gold quality
nucleus accumbens	UBERON:0001882	83.62	gold quality
Ammon’s horn	UBERON:0001954	83.43	gold quality
cerebellar vermis	UBERON:0004720	82.93	gold quality
neocortex	UBERON:0001950	82.88	gold quality
prefrontal cortex	UBERON:0000451	82.65	gold quality
caudate nucleus	UBERON:0001873	82.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.41	gold quality
frontal cortex	UBERON:0001870	82.38	gold quality
substantia nigra	UBERON:0002038	82.29	gold quality
cerebral cortex	UBERON:0000956	81.82	gold quality
telencephalon	UBERON:0001893	81.77	gold quality
midbrain	UBERON:0001891	81.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.30	gold quality
cartilage tissue	UBERON:0002418	81.25	gold quality
ganglionic eminence	UBERON:0004023	80.96	gold quality
pancreatic ductal cell	CL:0002079	80.56	silver quality
putamen	UBERON:0001874	80.55	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	583.31
E-MTAB-5061	yes	486.35
E-GEOD-84465	yes	236.69
E-GEOD-135922	yes	27.37
E-GEOD-137537	yes	8.06
E-ANND-3	no	1.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting C1QL1, 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-9-5P	100.00	72.28	2361
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4492	99.87	68.25	3611
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-5587-5P	99.07	68.58	838
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-1910-5P	97.42	66.36	844

Literature-anchored findings (GeneRIF, showing 2)

• Conserved recoding RNA editing of vertebrate C1q-related factor C1QL1. (PMID:19275900)
• We conclude that the underexpression of CRABP1 and the overexpression of LCN2 may be useful diagnostic biomarkers in thyroid tumours with questionable malignity, and the overexpression of LCN2 and C1QL1 may be useful for prognostic purposes. (PMID:29321030)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1ql1	ENSDARG00000043436
mus_musculus	C1ql1	ENSMUSG00000045532
rattus_norvegicus	C1ql1	ENSRNOG00000002963

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), 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

C1q-related factor — O75973 (reviewed: O75973)

Alternative names: C1q and tumor necrosis factor-related protein 14, Complement component 1 Q subcomponent-like 1

All UniProt accessions (1): O75973

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. Interacts with ADGRB3. Forms heterooligomers with C1QL4, when proteins are coexpressed; this interaction does not occur after secretion.

Subcellular location. Secreted.

Tissue specificity. Expressed in brainstem.

RefSeq proteins (1): NP_006679* (*=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 (7 total): domain 2, compositionally biased region 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-O75973-F1	79.26	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 136 (showing top): CREL_01, WANG_CLIM2_TARGETS_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, MCLACHLAN_DENTAL_CARIES_UP, PAX4_01, GOCC_COLLAGEN_TRIMER, GOBP_NEURON_MATURATION, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING, NFKB_Q6, GOBP_ANATOMICAL_STRUCTURE_MATURATION

GO Biological Process (5): locomotory behavior (GO:0007626), neuron remodeling (GO:0016322), motor learning (GO:0061743), maintenance of synapse structure (GO:0099558), regulation of synapse pruning (GO:1905806)

GO Molecular Function (2): signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (7): collagen trimer (GO:0005581), cytoplasm (GO:0005737), synaptic cleft (GO:0043083), climbing fiber (GO:0044301), presynapse (GO:0098793), cerebellar climbing fiber to Purkinje cell synapse (GO:0150053), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
behavior	1
neuron maturation	1
learning	1
cell junction maintenance	1
synapse organization	1
regulation of synapse organization	1
synapse pruning	1
protein binding	1
binding	1
protein-containing complex	1
intracellular anatomical structure	1
extracellular region	1
axon	1
synapse	1
asymmetric, glutamatergic, excitatory synapse	1

Protein interactions and networks

STRING

1156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QL1	ADGRB3	O60242	798
C1QL1	C1QTNF8	P60827	492
C1QL1	C1QTNF1	Q9BXJ1	490
C1QL1	C1QTNF9	P0C862	468
C1QL1	COL25A1	Q9BXS0	449
C1QL1	NBEAL1	Q6ZS30	447
C1QL1	COL24A1	Q17RW2	445
C1QL1	GLDN	Q6ZMI3	440
C1QL1	COL9A1	P20849	439
C1QL1	CTHRC1	Q96CG8	438
C1QL1	C1R	P00736	428
C1QL1	C1QL2	Q7Z5L3	422
C1QL1	COL2A1	P02458	399
C1QL1	COL15A1	P39059	394
C1QL1	C1QL4	Q86Z23	388

IntAct

70 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
COL10A1	C1QL1	psi-mi:“MI:0914”(association)	0.530
CD1E	SUSD5	psi-mi:“MI:0914”(association)	0.530
ZACN	GPAA1	psi-mi:“MI:0914”(association)	0.530
YKT6	C1QL1	psi-mi:“MI:0914”(association)	0.530
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
CBLN4	C1QL1	psi-mi:“MI:0914”(association)	0.530
ADIPOQ	C1QL1	psi-mi:“MI:0914”(association)	0.530
LAIR2	LAMA5	psi-mi:“MI:0914”(association)	0.530
C1QL1	C1QTNF8	psi-mi:“MI:0915”(physical association)	0.400
C1QL1	C1qtnf1	psi-mi:“MI:0915”(physical association)	0.400
C1QL1	C1ql2	psi-mi:“MI:0915”(physical association)	0.400
C1qtnf9	C1QL1	psi-mi:“MI:0915”(physical association)	0.400
TMED6	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
ICAM2	NRP1	psi-mi:“MI:0914”(association)	0.350
HTR3A	GPAA1	psi-mi:“MI:0914”(association)	0.350
MSRB3	SPOP	psi-mi:“MI:0914”(association)	0.350
CBLN4	ADAM11	psi-mi:“MI:0914”(association)	0.350
F7	C1QL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): C1QL1 (Reconstituted Complex), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), C1QL1 (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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	11.7×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
monoatomic ion transmembrane transport	6	18.4×	3e-04
adaptive immune response	6	7.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1342375	NC_000017.11:g.44846894_44962103del	Pathogenic

SpliceAI

414 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44960363:CGCAC:C	acceptor_gain	1.0000
17:44960364:GCAC:G	acceptor_gain	1.0000
17:44960365:CAC:C	acceptor_gain	1.0000
17:44960365:CACC:C	acceptor_gain	1.0000
17:44960366:AC:A	acceptor_gain	1.0000
17:44960367:CC:C	acceptor_gain	1.0000
17:44960367:CCTG:C	acceptor_loss	1.0000
17:44960368:CTGCG:C	acceptor_loss	1.0000
17:44960369:T:C	acceptor_loss	1.0000
17:44960374:G:GC	acceptor_gain	1.0000
17:44960382:C:CT	acceptor_gain	1.0000
17:44960385:G:T	acceptor_gain	1.0000
17:44960368:C:CC	acceptor_gain	0.9900
17:44960372:G:T	acceptor_gain	0.9900
17:44960374:G:C	acceptor_gain	0.9900
17:44960384:C:CT	acceptor_gain	0.9900
17:44967482:A:AC	donor_gain	0.9900
17:44967483:C:CC	donor_gain	0.9900
17:44960365:CACCT:C	acceptor_gain	0.9700
17:44967479:CATA:C	donor_gain	0.9700
17:44960364:GCACC:G	acceptor_gain	0.9600
17:44960366:ACCTG:A	acceptor_gain	0.9600
17:44960367:CCTGC:C	acceptor_gain	0.9600
17:44967448:CCAC:C	donor_loss	0.9600
17:44967450:ACC:A	donor_loss	0.9600
17:44967451:C:CT	donor_loss	0.9600
17:44967452:C:G	donor_loss	0.9600
17:44967557:G:A	donor_gain	0.9600
17:44960368:C:A	acceptor_gain	0.9500
17:44960368:C:T	acceptor_gain	0.9400

AlphaMissense

1677 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44960206:G:C	F253L	1.000
17:44960206:G:T	F253L	1.000
17:44960208:A:G	F253L	1.000
17:44960210:C:T	G252D	1.000
17:44960211:C:G	G252R	1.000
17:44960214:A:G	S251P	1.000
17:44960216:A:G	F250S	1.000
17:44960221:G:C	S248R	1.000
17:44960221:G:T	S248R	1.000
17:44960223:T:G	S248R	1.000
17:44960225:T:C	Y247C	1.000
17:44960226:A:G	Y247H	1.000
17:44960243:C:T	G241D	1.000
17:44960247:G:C	H240D	1.000
17:44960264:A:G	L234P	1.000
17:44960276:A:T	V230D	1.000
17:44960294:A:G	L224P	1.000
17:44960300:A:G	L222P	1.000
17:44960308:G:C	S219R	1.000
17:44960308:G:T	S219R	1.000
17:44960310:T:G	S219R	1.000
17:44960311:G:C	N218K	1.000
17:44960311:G:T	N218K	1.000
17:44960314:G:C	S217R	1.000
17:44960314:G:T	S217R	1.000
17:44960316:T:G	S217R	1.000
17:44960318:G:T	A216D	1.000
17:44960324:T:A	D214V	1.000
17:44960342:T:A	D208V	1.000
17:44960342:T:G	D208A	1.000

dbSNP variants (sampled 300 via entrez): RS1000160920 (17:44967748 C>T), RS1000236506 (17:44960029 G>A,T), RS1000903668 (17:44961340 C>T), RS1001254748 (17:44959590 T>A), RS1001322378 (17:44969873 T>G), RS1001353090 (17:44969621 C>G,T), RS1001798767 (17:44969641 G>A,C), RS1001830093 (17:44969937 A>C), RS1001940071 (17:44962437 T>G), RS1002234374 (17:44965075 C>T), RS1002312119 (17:44962104 G>C), RS1002315011 (17:44966778 T>C,G), RS1002610014 (17:44965335 A>G), RS1002614243 (17:44965252 T>C), RS1002892738 (17:44962212 A>G,T)

Disease associations

OMIM: gene MIM:611586 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002058_13	DNA methylation (variation)	2.000000e-06
GCST003013_13	White matter hyperintensity burden	1.000000e-06
GCST003013_27	White matter hyperintensity burden	2.000000e-07
GCST004412_12	Craniofacial microsomia	9.000000e-06
GCST006585_2810	Blood protein levels	3.000000e-32
GCST007576_242	Chronotype	4.000000e-10
GCST008916_39	Asthma	8.000000e-12
GCST010703_91	Brain morphology (MOSTest)	2.000000e-65
GCST010922_12	Hip bone mineral density and total body fat mass (bivariate analysis)	5.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0022599	DNA methylation
EFO:0005665	white matter hyperintensity measurement
EFO:0008328	chronotype measurement
EFO:0004346	neuroimaging measurement
EFO:0007702	hip bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Copper	increases expression, affects cotreatment, affects binding	2
Particulate Matter	increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
NSC 689534	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	increases expression	1
Chelating Agents	affects binding, increases expression	1
Cisplatin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Gold Compounds	decreases methylation, 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.