C1QTNF9B

Summary

C1QTNF9B (C1q and TNF related 9B, HGNC:34072) is a protein-coding gene on chromosome 13q12.12, encoding Complement C1q and tumor necrosis factor-related protein 9B (B2RNN3). Probable adipokine.

Predicted to enable hormone activity and identical protein binding activity. Predicted to act upstream of or within several processes, including negative regulation of cell size; positive regulation of cellular response to insulin stimulus; and positive regulation of protein serine/threonine kinase activity. Predicted to be located in extracellular space. Predicted to be part of collagen trimer.

Source: NCBI Gene 387911 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 80 total
• MANE Select transcript: NM_001007537

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34072
Approved symbol	C1QTNF9B
Name	C1q and TNF related 9B
Location	13q12.12
Locus type	gene with protein product
Status	Approved
Aliases	CTRP9B
Ensembl gene	ENSG00000205863
Ensembl biotype	protein_coding
OMIM	614148
Entrez	387911

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000382137, ENST00000382145, ENST00000556521, ENST00000713589

RefSeq mRNA: 1 — MANE Select: NM_001007537 NM_001007537

CCDS: CCDS31947

Canonical transcript exons

ENST00000713589 — 5 exons

Exon	Start	End
ENSE00001491054	23897122	23897226
ENSE00001762139	23891099	23892061
ENSE00001771083	23897418	23897502
ENSE00003683302	23894139	23894201
ENSE00004020393	23896821	23897006

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 88.79.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.67	gold quality
skin of leg	UBERON:0001511	71.39	gold quality
zone of skin	UBERON:0000014	70.98	gold quality
skin of abdomen	UBERON:0001416	70.32	gold quality
Ammon’s horn	UBERON:0001954	68.94	gold quality
right testis	UBERON:0004534	67.01	gold quality
stromal cell of endometrium	CL:0002255	66.49	gold quality
left testis	UBERON:0004533	66.21	gold quality
testis	UBERON:0000473	66.19	gold quality
hypothalamus	UBERON:0001898	62.93	gold quality
skeletal muscle tissue	UBERON:0001134	61.27	gold quality
prostate gland	UBERON:0002367	60.50	gold quality
spleen	UBERON:0002106	60.22	gold quality
muscle tissue	UBERON:0002385	60.11	gold quality
pituitary gland	UBERON:0000007	57.98	gold quality
smooth muscle tissue	UBERON:0001135	56.80	gold quality
temporal lobe	UBERON:0001871	56.76	gold quality
amygdala	UBERON:0001876	56.67	gold quality
minor salivary gland	UBERON:0001830	56.18	gold quality
anterior cingulate cortex	UBERON:0009835	56.06	gold quality
adenohypophysis	UBERON:0002196	55.82	gold quality
heart left ventricle	UBERON:0002084	55.57	gold quality
saliva-secreting gland	UBERON:0001044	54.55	gold quality
muscle of leg	UBERON:0001383	54.46	gold quality
lower esophagus	UBERON:0013473	54.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	54.35	gold quality
colonic epithelium	UBERON:0000397	53.31	silver quality
right frontal lobe	UBERON:0002810	53.27	gold quality
esophagus	UBERON:0001043	53.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting C1QTNF9B, 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-1193	100.00	65.93	529
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-11181-3P	99.75	66.38	2205

Literature-anchored findings (GeneRIF, showing 2)

• two novel human C1q/TNF family members, designated as CTRP8 and CTRP9B were described. (PMID:19666007)
• C1q/TNF-related protein-9 suppresses inflammation in synovial cells from patients with osteoarthritis. (PMID:34514937)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1qtnf9	ENSDARG00000058318
mus_musculus	C1qtnf9	ENSMUSG00000071347
rattus_norvegicus	C1qtnf9	ENSRNOG00000013793

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), C1QL4 (ENSG00000186897), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Complement C1q and tumor necrosis factor-related protein 9B — B2RNN3 (reviewed: B2RNN3)

Alternative names: C1q/TNF-related protein 9B, Complement C1q and tumor necrosis factor-related protein 9-like

All UniProt accessions (2): A0A0C4DFX8, B2RNN3

UniProt curated annotations — full annotation on UniProt →

Function. Probable adipokine. Activates AMPK, AKT, and p44/42 MAPK signaling pathways.

Subunit / interactions. Interacts with CTRP9A and ADIPOQ. Forms heterotrimers and heterooligomeric complexes with CTRP9A.

Subcellular location. Secreted.

Tissue specificity. Expressed at low levels. Not expressed in adipose tissues.

Isoforms (2)

UniProt ID	Names	Canonical?
B2RNN3-1	1	yes
B2RNN3-2	2

RefSeq proteins (1): NP_001007538* (*=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 (12 total): domain 4, compositionally biased region 3, splice variant 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-B2RNN3-F1	66.75	0.41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (showing top): GOCC_COLLAGEN_TRIMER, MIR548AA_MIR548AP_3P_MIR548T_3P, MIR4427, MIR766_5P, MIR2054, MIR376C_3P, MIR6868_5P, WP_13Q1212_COPY_NUMBER_VARIATION, NABA_SECRETED_FACTORS, NABA_MATRISOME_ASSOCIATED, NABA_MATRISOME, chr13q12

GO Biological Process (0):

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
binding	1
cellular anatomical structure	1
protein-containing complex	1

Protein interactions and networks

STRING

260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QTNF9B	MIPEP	Q99797	591
C1QTNF9B	FAM229A	H3BQW9	582
C1QTNF9B	CLEC18C	Q8NCF0	505
C1QTNF9B	CYP27C1	Q4G0S4	393
C1QTNF9B	CDC42EP5	Q6NZY7	312
C1QTNF9B	SGCG	Q13326	307
C1QTNF9B	ZC3H11B	A0A1B0GTU1	306
C1QTNF9B	SNTB1	Q13884	293
C1QTNF9B	C1QTNF12	Q5T7M4	273
C1QTNF9B	C1QTNF8	P60827	260
C1QTNF9B	TSKU	Q8WUA8	256
C1QTNF9B	EPDR1	Q9UM22	249
C1QTNF9B	SLITRK6	Q9H5Y7	247
C1QTNF9B	KRT23	Q9C075	231
C1QTNF9B	NIPA2	Q8N8Q9	227

IntAct

12 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0915”(physical association)	0.780
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
C1QTNF9B	PLOD3	psi-mi:“MI:0914”(association)	0.530
C1QTNF9B	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.400
C1QTNF9B	RTCA	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	DNASE2	psi-mi:“MI:0914”(association)	0.350
GPR17	C1QTNF9B	psi-mi:“MI:0914”(association)	0.350

BioGRID (52): C1QTNF9B (Affinity Capture-MS), C1QTNF9B (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), MRC2 (Affinity Capture-MS), SIL1 (Affinity Capture-MS), SERPINE2 (Affinity Capture-MS), GDF11 (Affinity Capture-MS), COL2A1 (Affinity Capture-MS), CRTAP (Affinity Capture-MS), COL6A1 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), CTSF (Affinity Capture-MS), CDC6 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), PLOD3 (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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

418 predictions. Top by Δscore:

Variant	Effect	Δscore
13:23891997:T:TA	donor_gain	1.0000
13:23894135:TAAC:T	donor_loss	1.0000
13:23894136:AACC:A	donor_loss	1.0000
13:23894137:ACCTC:A	donor_loss	1.0000
13:23891943:T:A	donor_gain	0.9900
13:23892060:TCC:T	acceptor_loss	0.9900
13:23892061:CCTAA:C	acceptor_loss	0.9900
13:23892062:C:CC	acceptor_gain	0.9900
13:23892062:C:T	acceptor_loss	0.9900
13:23894137:A:AC	donor_gain	0.9900
13:23894138:C:CC	donor_gain	0.9900
13:23894138:CCT:C	donor_gain	0.9900
13:23894199:CTC:C	acceptor_gain	0.9900
13:23894200:TCC:T	acceptor_loss	0.9900
13:23894202:C:CC	acceptor_gain	0.9900
13:23894206:G:C	acceptor_gain	0.9900
13:23894206:G:GC	acceptor_gain	0.9900
13:23896816:AGTAC:A	donor_loss	0.9900
13:23896817:GTA:G	donor_loss	0.9900
13:23896818:TACCT:T	donor_loss	0.9900
13:23896819:A:T	donor_loss	0.9900
13:23896832:TTGTC:T	donor_gain	0.9900
13:23892059:CTC:C	acceptor_gain	0.9800
13:23894528:T:A	donor_gain	0.9800
13:23896815:GAGTA:G	donor_loss	0.9800
13:23891913:ATTCC:A	donor_gain	0.9700
13:23894197:TTCTC:T	acceptor_gain	0.9700
13:23894147:C:CA	donor_gain	0.9600
13:23894200:TC:T	acceptor_gain	0.9600
13:23894201:CC:C	acceptor_gain	0.9600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000670278 (13:23890839 C>A), RS1002215919 (13:23894433 C>T), RS1002953289 (13:23897762 G>A), RS1002983673 (13:23891033 CACAG>C), RS1003221177 (13:23893131 C>T), RS1003317465 (13:23892944 C>T), RS1003379241 (13:23898648 C>CCA), RS1004056298 (13:23895947 G>A,C), RS1004362717 (13:23896384 T>C), RS1006301482 (13:23895054 G>A), RS1006513499 (13:23897820 A>G), RS1006806761 (13:23894905 G>A), RS1007024933 (13:23892297 C>A,T), RS1007401642 (13:23893670 A>C,G), RS1007719397 (13:23893854 A>G)

Disease associations

OMIM: gene MIM:614148 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001088_1	Myopia (pathological)	2.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004207	pathological myopia

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	1
abrine	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists