CBLN3

Summary

CBLN3 (cerebellin 3 precursor, HGNC:20146) is a protein-coding gene on chromosome 14q12, encoding Cerebellin-3 (Q6UW01). May be involved in synaptic functions in the CNS.

Members of the precerebellin family, such as CBLN3, contain a cerebellin motif (see CBLN1; MIM 600432) and a C-terminal C1q signature domain (see MIM 120550) that mediates trimeric assembly of atypical collagen complexes. However, precerebellins do not contain a collagen motif, suggesting that they are not conventional components of the extracellular matrix (Pang et al., 2000 [PubMed 10964938]).

Source: NCBI Gene 643866 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001039771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20146
Approved symbol	CBLN3
Name	cerebellin 3 precursor
Location	14q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000139899
Ensembl biotype	protein_coding
OMIM	612978
Entrez	643866

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000267406, ENST00000555436, ENST00000859360, ENST00000859361

RefSeq mRNA: 1 — MANE Select: NM_001039771 NM_001039771

CCDS: CCDS32057

Canonical transcript exons

ENST00000267406 — 3 exons

Exon	Start	End
ENSE00000940676	24428755	24429668
ENSE00000940677	24428286	24428405
ENSE00000940678	24426545	24427986

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 98.92.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3957 / max 32.6245, expressed in 160 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142604	0.3957	160

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	98.92	gold quality
cerebellum	UBERON:0002037	98.33	gold quality
cerebellar cortex	UBERON:0002129	98.31	gold quality
cerebellar hemisphere	UBERON:0002245	98.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.81	gold quality
right adrenal gland cortex	UBERON:0035827	87.48	gold quality
right adrenal gland	UBERON:0001233	86.34	gold quality
pons	UBERON:0000988	86.18	gold quality
left adrenal gland cortex	UBERON:0035825	84.06	gold quality
left adrenal gland	UBERON:0001234	83.70	gold quality
adrenal cortex	UBERON:0001235	83.22	gold quality
adrenal gland	UBERON:0002369	81.52	gold quality
lymph node	UBERON:0000029	80.98	gold quality
ileal mucosa	UBERON:0000331	79.27	silver quality
spleen	UBERON:0002106	79.06	gold quality
left ovary	UBERON:0002119	78.23	gold quality
vermiform appendix	UBERON:0001154	78.03	gold quality
tibialis anterior	UBERON:0001385	77.89	silver quality
right ovary	UBERON:0002118	77.66	gold quality
adrenal tissue	UBERON:0018303	77.01	gold quality
right coronary artery	UBERON:0001625	76.93	gold quality
stromal cell of endometrium	CL:0002255	76.28	gold quality
omental fat pad	UBERON:0010414	76.28	gold quality
peritoneum	UBERON:0002358	76.22	gold quality
adult organism	UBERON:0007023	76.17	gold quality
left coronary artery	UBERON:0001626	75.61	gold quality
apex of heart	UBERON:0002098	75.57	gold quality
gall bladder	UBERON:0002110	75.00	gold quality
adipose tissue of abdominal region	UBERON:0007808	74.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting CBLN3, 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-12118	100.00	65.88	1270
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-609	99.82	64.26	505
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-298	99.63	67.56	1916

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbln8	ENSDARG00000019294
danio_rerio	cbln10	ENSDARG00000023157
danio_rerio	cbln13	ENSDARG00000026904
danio_rerio	cbln9	ENSDARG00000030254
danio_rerio	cbln6	ENSDARG00000035718
danio_rerio	cbln5	ENSDARG00000053802
danio_rerio	cbln14	ENSDARG00000053845
danio_rerio	cbln12	ENSDARG00000068232
danio_rerio	cbln11	ENSDARG00000086654
danio_rerio	cbln20	ENSDARG00000087476
danio_rerio	si:ch211-142d6.2	ENSDARG00000088625
danio_rerio	cbln17	ENSDARG00000088911
danio_rerio	cbln18	ENSDARG00000090969
danio_rerio	cbln7	ENSDARG00000095040
danio_rerio	si:dkeyp-110c7.4	ENSDARG00000100476
danio_rerio	si:dkeyp-74b6.2	ENSDARG00000115070
mus_musculus	Cbln3	ENSMUSG00000040380
rattus_norvegicus	Cbln3	ENSRNOG00000020503

Paralogs (3): CBLN4 (ENSG00000054803), CBLN1 (ENSG00000102924), CBLN2 (ENSG00000141668)

Protein

Protein identifiers

Cerebellin-3 — Q6UW01 (reviewed: Q6UW01)

All UniProt accessions (2): Q6UW01, G3V2Y8

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in synaptic functions in the CNS.

Subunit / interactions. Heterohexamer; disulfide-linked heterotrimers. Interacts with CBLN1. May also form oligomers with CBLN2 and CBLN4.

Subcellular location. Endoplasmic reticulum. Golgi apparatus. cis-Golgi network. Secreted. Synapse.

RefSeq proteins (1): NP_001034860* (*=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 (7 total): disulfide bond 2, signal peptide 1, chain 1, domain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UW01-F1	77.67	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 45, 49

Glycosylation sites (1): 90

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): GOBP_CELLULAR_COMPONENT_MAINTENANCE, chr14q12, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_SYNAPTIC_SIGNALING, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, GOCC_EXCITATORY_SYNAPSE, LEIN_CEREBELLUM_MARKERS, GOCC_SYNAPSE, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, GOBP_SYNAPSE_ORGANIZATION, GOBP_CELL_JUNCTION_MAINTENANCE

GO Biological Process (1): maintenance of synapse structure (GO:0099558)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), synaptic cleft (GO:0043083), synapse (GO:0045202), parallel fiber to Purkinje cell synapse (GO:0098688), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cell junction maintenance	1
synapse organization	1
binding	1
extracellular region	1
cell junction	1
excitatory synapse	1

Protein interactions and networks

STRING

808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBLN3	GRID2	O43424	861
CBLN3	TMEM69	Q5SWH9	581
CBLN3	CCDC137	Q6PK04	573
CBLN3	NYNRIN	Q9P2P1	558
CBLN3	CLEC19A	Q6UXS0	555
CBLN3	ZC3H10	Q96K80	533
CBLN3	STXBP6	Q8NFX7	524
CBLN3	STOML1	Q9UBI4	514
CBLN3	SDR39U1	Q9NRG7	511
CBLN3	PECR	Q9BY49	460
CBLN3	CBLN2	Q8IUK8	455
CBLN3	LAMB4	A4D0S4	440
CBLN3	BEAN1	Q3B7T3	432
CBLN3	RNF17	Q9BXT8	408
CBLN3	FAT2	Q9NYQ8	407
CBLN3	CYP4V2	Q6ZWL3	407

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: D4AB34, O54907, O55237, O75888, O77510, O95150, P01374, P01375, P04924, P09225, P10154, P19101, P26445, P29553, P32970, P33620, P41273, P48094, P51435, P59695, P61125, P63307, P79337, P98087, Q06332, Q06600, Q17QF9, Q19LH4, Q1WM27, Q3ZDR4, Q5TM20, Q5UBV8, Q5WR07, Q6PGN1, Q6UW01, Q75N23, Q861W5, Q8BGU2, Q8HZD9, Q8IUK8

Diamond homologs: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, O75973, O88992, P02745, P02746, P02747, P08125, P0C862, P14282, P23206, P23435, P25067, P25318, P27658, P31720, P63182, P83371, P86437, P98085, P98086, P98087, Q00780, Q02105, Q03692, Q05306, Q05A80, Q0II24, Q15848, Q17QF9, Q2KIV9, Q3Y5Z3, Q4ZJM7, Q4ZJM9, Q4ZJN1, Q5E9E3, Q5FVH0, Q5RJ80

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

804 predictions. Top by Δscore:

Variant	Effect	Δscore
14:24428284:AC:A	donor_loss	1.0000
14:24428285:C:G	donor_loss	1.0000
14:24428307:CACCT:C	donor_gain	1.0000
14:24430927:CCAAG:C	donor_loss	1.0000
14:24430928:CAAG:C	donor_loss	1.0000
14:24430929:AAGG:A	donor_loss	1.0000
14:24430930:AGGT:A	donor_loss	1.0000
14:24430931:GGTGA:G	donor_loss	1.0000
14:24430932:G:GA	donor_loss	1.0000
14:24430933:T:G	donor_loss	1.0000
14:24427983:TCACC:T	acceptor_loss	0.9900
14:24427986:CCT:C	acceptor_loss	0.9900
14:24427987:CTGGG:C	acceptor_loss	0.9900
14:24428287:TGG:T	donor_gain	0.9900
14:24428309:CCT:C	donor_gain	0.9900
14:24428311:TTC:T	donor_gain	0.9900
14:24430708:TTCCA:T	acceptor_loss	0.9900
14:24430709:TCCAG:T	acceptor_loss	0.9900
14:24430710:CCA:C	acceptor_loss	0.9900
14:24430711:CAGGG:C	acceptor_loss	0.9900
14:24430712:A:AG	acceptor_gain	0.9900
14:24430712:A:T	acceptor_loss	0.9900
14:24430712:AG:A	acceptor_gain	0.9900
14:24430712:AGG:A	acceptor_gain	0.9900
14:24430713:G:GG	acceptor_gain	0.9900
14:24430713:GG:G	acceptor_gain	0.9900
14:24430713:GGG:G	acceptor_gain	0.9900
14:24430713:GGGCT:G	acceptor_gain	0.9900
14:24430911:G:GT	donor_gain	0.9900
14:24430912:A:T	donor_gain	0.9900

AlphaMissense

1282 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:24428329:A:G	F126S	1.000
14:24427811:C:T	G199D	0.999
14:24427817:A:G	F197S	0.999
14:24427970:T:A	N146I	0.999
14:24428336:A:C	Y124D	0.999
14:24428359:A:C	F116C	0.999
14:24428359:A:G	F116S	0.999
14:24428380:A:C	F109C	0.999
14:24428761:G:C	F98L	0.999
14:24428761:G:T	F98L	0.999
14:24428762:A:C	F98C	0.999
14:24428762:A:G	F98S	0.999
14:24428763:A:G	F98L	0.999
14:24428833:A:C	F74L	0.999
14:24428833:A:T	F74L	0.999
14:24428834:A:C	F74C	0.999
14:24428834:A:G	F74S	0.999
14:24428835:A:G	F74L	0.999
14:24427816:G:C	F197L	0.998
14:24427816:G:T	F197L	0.998
14:24427817:A:C	F197C	0.998
14:24427818:A:G	F197L	0.998
14:24427831:C:A	W192C	0.998
14:24427831:C:G	W192C	0.998
14:24427889:A:C	L173W	0.998
14:24427945:A:C	F154L	0.998
14:24427945:A:T	F154L	0.998
14:24427947:A:G	F154L	0.998
14:24427979:A:G	L143P	0.998
14:24428341:C:A	G122V	0.998

dbSNP variants (sampled 300 via entrez): RS1000300505 (14:24428239 C>T), RS1000564660 (14:24426607 C>A,T), RS1003624867 (14:24428412 G>A,T), RS1003740892 (14:24428729 C>G,T), RS1004295122 (14:24427355 G>A), RS1004817321 (14:24427503 A>C,G), RS1005706606 (14:24428686 G>A), RS1006090366 (14:24430245 T>C), RS1006701909 (14:24430054 G>A), RS1007637874 (14:24429806 G>C), RS1007796611 (14:24430297 G>A), RS1007880557 (14:24427306 A>C), RS1008432422 (14:24426990 A>C,G), RS1009595876 (14:24428391 C>T), RS1010145549 (14:24426997 G>A,T)

Disease associations

OMIM: gene MIM:612978 | 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
GCST000759_4	LDL cholesterol	4.000000e-11
GCST002898_9	LDL cholesterol	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
afuresertib	increases expression	1
dicrotophos	increases expression	1
bisphenol A	decreases expression	1
butyraldehyde	decreases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Estradiol	decreases expression	1
Folic Acid	decreases expression	1
Lead	decreases expression	1
Smoke	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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