C1QL4

Summary

C1QL4 (complement C1q like 4, HGNC:31416) is a protein-coding gene on chromosome 12q13.12, encoding Complement C1q-like protein 4 (Q86Z23). May regulate the number of excitatory synapses that are formed on hippocampus neurons.

Predicted to enable identical protein binding activity. Predicted to act upstream of or within negative regulation of ERK1 and ERK2 cascade; negative regulation of fat cell differentiation; and negative regulation of fibroblast proliferation. Predicted to be located in extracellular space. Predicted to be part of collagen trimer.

Source: NCBI Gene 338761 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001008223

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31416
Approved symbol	C1QL4
Name	complement C1q like 4
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	C1QTNF11, CTRP11
Ensembl gene	ENSG00000186897
Ensembl biotype	protein_coding
OMIM	615229
Entrez	338761

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000334221, ENST00000850913

RefSeq mRNA: 1 — MANE Select: NM_001008223 NM_001008223

CCDS: CCDS31793

Canonical transcript exons

ENST00000334221 — 2 exons

Exon	Start	End
ENSE00001335066	49332409	49333233
ENSE00001335070	49335941	49337188

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 82.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3067 / max 28.1958, expressed in 172 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130837	0.3067	172

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.11	gold quality
calcaneal tendon	UBERON:0003701	69.85	gold quality
right testis	UBERON:0004534	60.25	gold quality
left testis	UBERON:0004533	60.04	gold quality
testis	UBERON:0000473	59.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	52.66	gold quality
hypothalamus	UBERON:0001898	52.45	gold quality
vagina	UBERON:0000996	51.73	gold quality
left lobe of thyroid gland	UBERON:0001120	51.69	gold quality
thyroid gland	UBERON:0002046	51.67	gold quality
temporal lobe	UBERON:0001871	50.31	gold quality
amygdala	UBERON:0001876	50.23	gold quality
right lobe of thyroid gland	UBERON:0001119	48.86	gold quality
substantia nigra	UBERON:0002038	48.30	gold quality
colonic epithelium	UBERON:0000397	45.01	gold quality
prefrontal cortex	UBERON:0000451	44.74	gold quality
ventricular zone	UBERON:0003053	44.28	silver quality
skin of leg	UBERON:0001511	42.87	gold quality
ectocervix	UBERON:0012249	42.60	gold quality
zone of skin	UBERON:0000014	42.49	gold quality
bone marrow cell	CL:0002092	42.16	gold quality
frontal cortex	UBERON:0001870	41.76	silver quality
anterior cingulate cortex	UBERON:0009835	41.62	gold quality
skin of abdomen	UBERON:0001416	41.60	gold quality
kidney	UBERON:0002113	41.13	gold quality
cerebral cortex	UBERON:0000956	40.97	gold quality
sural nerve	UBERON:0015488	40.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	40.95	silver quality
adult mammalian kidney	UBERON:0000082	40.91	gold quality
nucleus accumbens	UBERON:0001882	40.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting C1QL4, 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-513A-5P	100.00	69.77	2465
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-1470	98.11	63.53	399
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-4652-5P	96.46	64.22	553
HSA-MIR-139-3P	95.24	63.10	316

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1ql4a	ENSDARG00000011549
danio_rerio	c1ql4b	ENSDARG00000055317
mus_musculus	C1ql4	ENSMUSG00000001076
rattus_norvegicus	C1ql4	ENSRNOG00000060020

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), 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), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Complement C1q-like protein 4 — Q86Z23 (reviewed: Q86Z23)

Alternative names: C1q and tumor necrosis factor-related protein 11

All UniProt accessions (2): A0A3B0INP7, Q86Z23

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. May inhibit adipocyte differentiation at an early stage of the process.

Subunit / interactions. Forms homooligomers, predominantly dimers or trimers. Forms heterooligomers with C1QL1, C1QL2 and C1QL3, when proteins are coexpressed; this interaction does not occur after secretion. Interacts with ADGRB3.

Subcellular location. Secreted.

Tissue specificity. Highest expression levels in testis and adipose tissue, lower levels in skeletal muscle and kidney.

RefSeq proteins (1): NP_001008224* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00386

UniProt features (6 total): domain 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-Q86Z23-F1	81.51	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOCC_COLLAGEN_TRIMER, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEGATIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_CELL_CELL_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_CELL_JUNCTION_ORGANIZATION, CCTGTGA_MIR513, GOBP_SYNAPTIC_SIGNALING, GOBP_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, AACTGGA_MIR145

GO Biological Process (5): negative regulation of fat cell differentiation (GO:0045599), fibroblast proliferation (GO:0048144), negative regulation of fibroblast proliferation (GO:0048147), ERK1 and ERK2 cascade (GO:0070371), negative regulation of ERK1 and ERK2 cascade (GO:0070373)

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

GO Cellular Component (3): collagen trimer (GO:0005581), obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
cell population proliferation	1
negative regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
MAPK cascade	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
protein binding	1
binding	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QL4	ERP44	Q9BS26	508
C1QL4	YPEL1	O60688	498
C1QL4	ADGRB3	O60242	491
C1QL4	C1QTNF8	P60827	478
C1QL4	C1QTNF1	Q9BXJ1	458
C1QL4	WDR26	Q9H7D7	455
C1QL4	C1QTNF9	P0C862	449
C1QL4	COL25A1	Q9BXS0	448
C1QL4	FCN2	Q15485	439
C1QL4	C1QTNF12	Q5T7M4	434
C1QL4	MXRA8	Q9BRK3	429
C1QL4	COL15A1	P39059	428
C1QL4	BCAP29	Q9UHQ4	407
C1QL4	GLDN	Q6ZMI3	405
C1QL4	VANGL2	Q9ULK5	398

IntAct

108 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
C1QL4	CERS4	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	GOLM1	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	TMEM179B	psi-mi:“MI:0915”(physical association)	0.560
SGTA	C1QL4	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	FATE1	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	MFF	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	C1QL4	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	SGTB	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
SCARA5	C1QL4	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	FNDC9	psi-mi:“MI:0915”(physical association)	0.560
CD53	C1QL4	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	RHCG	psi-mi:“MI:0915”(physical association)	0.560
C1QL4	GPR152	psi-mi:“MI:0915”(physical association)	0.560
TMEM179B	C1QL4	psi-mi:“MI:0915”(physical association)	0.560
TRHR	C1QL4	psi-mi:“MI:0915”(physical association)	0.560
IL10RA	C1QL4	psi-mi:“MI:0915”(physical association)	0.560
LEUTX	C1QL4	psi-mi:“MI:0915”(physical association)	0.560
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530

BioGRID (88): C1QL4 (Affinity Capture-MS), DUS3L (Affinity Capture-MS), KLHL11 (Affinity Capture-MS), C1QL4 (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), SRC (Affinity Capture-MS), VHL (Affinity Capture-MS), PON2 (Affinity Capture-MS), C1QL4 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), C9orf41 (Affinity Capture-MS), C1QL4 (Affinity Capture-MS), BTN2A2 (Affinity Capture-MS), C1QL4 (Affinity Capture-MS), C12orf75 (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 85 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
Collagen biosynthesis and modifying enzymes	5	15.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

139 predictions. Top by Δscore:

Variant	Effect	Δscore
12:49333229:CGGAC:C	acceptor_gain	1.0000
12:49333233:CCT:C	acceptor_loss	1.0000
12:49333234:C:A	acceptor_loss	1.0000
12:49333234:C:CC	acceptor_gain	1.0000
12:49333238:C:CT	acceptor_gain	1.0000
12:49333230:GGAC:G	acceptor_gain	0.9900
12:49333239:G:T	acceptor_gain	0.9900
12:49335935:TCTCA:T	donor_loss	0.9900
12:49335936:CTCAC:C	donor_loss	0.9900
12:49335937:TCAC:T	donor_loss	0.9900
12:49335938:CA:C	donor_loss	0.9900
12:49335939:A:AT	donor_loss	0.9900
12:49333232:AC:A	acceptor_gain	0.9800
12:49333233:CC:C	acceptor_gain	0.9800
12:49335939:A:AC	donor_gain	0.9800
12:49335940:C:CC	donor_gain	0.9800
12:49335940:CCTGT:C	donor_gain	0.9700
12:49333231:GAC:G	acceptor_gain	0.9600
12:49336136:C:CT	acceptor_gain	0.9400
12:49336135:CCGCG:C	acceptor_gain	0.9300
12:49333089:TG:T	donor_gain	0.9200
12:49336136:C:T	acceptor_gain	0.8700
12:49333119:T:A	donor_gain	0.8000
12:49336139:G:C	acceptor_gain	0.8000
12:49336138:C:CT	acceptor_gain	0.7900
12:49335472:T:TA	donor_gain	0.7800
12:49335783:T:TA	donor_gain	0.7500
12:49336046:G:A	donor_gain	0.7500
12:49334826:C:CA	donor_gain	0.7200
12:49333231:GACC:G	acceptor_gain	0.7100

AlphaMissense

1533 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:49333076:C:T	G232D	1.000
12:49333081:G:C	F230L	1.000
12:49333081:G:T	F230L	1.000
12:49333082:A:G	F230S	1.000
12:49333083:A:G	F230L	1.000
12:49333087:G:C	S228R	1.000
12:49333087:G:T	S228R	1.000
12:49333089:T:G	S228R	1.000
12:49333091:T:C	Y227C	1.000
12:49333092:A:G	Y227H	1.000
12:49333160:A:G	L204P	1.000
12:49333166:A:G	L202P	1.000
12:49333180:G:C	S197R	1.000
12:49333180:G:T	S197R	1.000
12:49333182:T:G	S197R	1.000
12:49333184:G:T	A196D	1.000
12:49333222:G:C	S183R	1.000
12:49333222:G:T	S183R	1.000
12:49333224:T:G	S183R	1.000
12:49335957:A:G	L174P	1.000
12:49335965:C:A	W171C	1.000
12:49335965:C:G	W171C	1.000
12:49335967:A:G	W171R	1.000
12:49335967:A:T	W171R	1.000
12:49336011:A:G	F156S	1.000
12:49336018:A:C	Y154D	1.000
12:49336034:G:C	C148W	1.000
12:49336035:C:T	C148Y	1.000
12:49336041:A:G	F146S	1.000
12:49336094:G:C	F128L	1.000

dbSNP variants (sampled 300 via entrez): RS1001323712 (12:49336550 T>C,G), RS1001857741 (12:49332265 C>A,T), RS1001862892 (12:49332237 G>A), RS1001928640 (12:49337794 A>G), RS1002096807 (12:49332476 G>A), RS1002325548 (12:49337159 C>T), RS1002697511 (12:49334716 G>A,C), RS1002805159 (12:49337640 C>T), RS1002859446 (12:49333612 G>A), RS1003101655 (12:49333807 A>C), RS1003335761 (12:49339009 G>A), RS1003395480 (12:49338656 A>T), RS1003409478 (12:49334531 C>T), RS1003957660 (12:49337267 G>A), RS1003988750 (12:49337606 T>A)

Disease associations

OMIM: gene MIM:615229 | 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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Cisplatin	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Zoledronic Acid	decreases expression	1
Aldehydes	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Niclosamide	increases expression	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Triclosan	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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