CREG2

Summary

CREG2 (cellular repressor of E1A stimulated genes 2, HGNC:14272) is a protein-coding gene on chromosome 2q11.2, encoding Protein CREG2 (Q8IUH2).

Predicted to be located in Golgi apparatus; endoplasmic reticulum; and extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 200407 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_153836

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14272
Approved symbol	CREG2
Name	cellular repressor of E1A stimulated genes 2
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175874
Ensembl biotype	protein_coding
OMIM	618540
Entrez	200407

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000324768, ENST00000486966, ENST00000495455

RefSeq mRNA: 1 — MANE Select: NM_153836 NM_153836

CCDS: CCDS2052

Canonical transcript exons

ENST00000324768 — 4 exons

Exon	Start	End
ENSE00001246894	101355253	101355366
ENSE00001246907	101345550	101351070
ENSE00001930395	101387017	101387503
ENSE00003692450	101383533	101383702

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 98.91.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8468 / max 258.1187, expressed in 552 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29945	3.3976	528
29944	0.2302	76
29943	0.1173	46
29946	0.1017	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 46	UBERON:0006483	98.91	gold quality
endothelial cell	CL:0000115	98.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.09	gold quality
superior frontal gyrus	UBERON:0002661	97.96	gold quality
postcentral gyrus	UBERON:0002581	97.62	gold quality
parietal lobe	UBERON:0001872	97.53	gold quality
middle temporal gyrus	UBERON:0002771	97.32	gold quality
entorhinal cortex	UBERON:0002728	96.50	gold quality
primary visual cortex	UBERON:0002436	95.77	gold quality
occipital lobe	UBERON:0002021	95.44	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.22	gold quality
prefrontal cortex	UBERON:0000451	93.78	gold quality
frontal cortex	UBERON:0001870	93.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.15	gold quality
cerebral cortex	UBERON:0000956	91.96	gold quality
neocortex	UBERON:0001950	91.81	gold quality
Ammon’s horn	UBERON:0001954	91.47	gold quality
right frontal lobe	UBERON:0002810	91.07	gold quality
anterior cingulate cortex	UBERON:0009835	90.63	gold quality
temporal lobe	UBERON:0001871	90.10	gold quality
pons	UBERON:0000988	88.12	gold quality
buccal mucosa cell	CL:0002336	85.78	gold quality
amygdala	UBERON:0001876	85.78	gold quality
forebrain	UBERON:0001890	83.10	gold quality
nucleus accumbens	UBERON:0001882	78.72	gold quality
superior vestibular nucleus	UBERON:0007227	78.15	gold quality
hypothalamus	UBERON:0001898	77.98	gold quality
brain	UBERON:0000955	77.67	gold quality
corpus callosum	UBERON:0002336	73.36	gold quality
medulla oblongata	UBERON:0001896	72.85	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	38.72
E-ANND-3	yes	5.37
E-GEOD-36552	no	6.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting CREG2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-579-3P	99.86	71.66	3628

Literature-anchored findings (GeneRIF, showing 1)

• CREG2 are putative secreted glycoproteins and may be novel neuronal extracellular molecules. (PMID:12408961)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	creg2	ENSDARG00000000666
mus_musculus	Creg2	ENSMUSG00000050967
rattus_norvegicus	Creg2	ENSRNOG00000013991
drosophila_melanogaster	CREG	FBGN0025456

Paralogs (1): CREG1 (ENSG00000143162)

Protein

Protein identifiers

Protein CREG2 — Q8IUH2 (reviewed: Q8IUH2)

Alternative names: Cellular repressor of E1A-stimulated genes 2

All UniProt accessions (1): Q8IUH2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Brain specific mainly in the limbic system and faintly in the spinal cord but not in cerebellum.

Post-translational modifications. It is not sure whether N-glycosylation is on Asn-165 and/or Asn-166.

Similarity. Belongs to the CREG family.

RefSeq proteins (1): NP_722578* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012349	Split_barrel_FMN-bd	Homologous_superfamily
IPR014631	CREG	Family
IPR055343	CREG_beta-barrel	Domain

Pfam: PF13883

UniProt features (6 total): glycosylation site 2, signal peptide 1, chain 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUH2-F1	72.48	0.46

Functional residue map

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

Glycosylation sites (2): 165, 166

Mutagenesis-validated functional residues (1):

Position	Phenotype
165–166	abolishes n-glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GTCAACC_MIR3805P, chr2q11, MEISSNER_NPC_HCP_WITH_H3K4ME2, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_UP, GSE13547_WT_VS_ZFX_KO_BCELL_UP, MIR664B_3P, MIR4753_3P, MIR513A_3P_MIR513C_3P, MIR627_3P, MIR3606_3P, MIR6844, MIR543, MIR7152_5P, MIR4703_5P, MIR130B_5P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (6): obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), extracellular region (GO:0005576), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CREG2	SREK1IP1	Q8N9Q2	519
CREG2	ZNF572	Q7Z3I7	496
CREG2	STPG4	Q8N801	472
CREG2	PCP2	Q8IVA1	462
CREG2	ZNF28	P17035	459
CREG2	SFXN3	Q9BWM7	454
CREG2	ZNF85	Q03923	450
CREG2	ZNF708	P17019	449
CREG2	LEMD3	Q9Y2U8	426
CREG2	SH3TC2	Q8TF17	425
CREG2	SREK1	Q8WXA9	418
CREG2	ZNF430	Q9H8G1	412
CREG2	WIPF1	O43516	412
CREG2	P2RX1	P51575	405
CREG2	CLASP2	O75122	399

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CREG2	GLDC	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (4): CREG2 (Affinity Capture-RNA), GLDC (Affinity Capture-MS), CREG2 (Affinity Capture-MS), CREG2 (Positive Genetic)

ESM2 similar proteins: A0JJZ6, G1T7U7, H0VCJ6, O08841, O35448, O70489, O75629, O88668, P09531, P13284, P68827, Q02083, Q0J6H8, Q0P5H1, Q10S70, Q1JQA0, Q3SZL5, Q5M872, Q5VSG8, Q5XI31, Q5ZJ73, Q5ZMM1, Q65XS5, Q67WE2, Q69ZQ1, Q6NSJ0, Q6P1J0, Q6PD26, Q6W3E9, Q6W3F0, Q6YX89, Q6ZIF9, Q75UG4, Q7X6J9, Q7Z4N8, Q84TW8, Q8BGC9, Q8BJ48, Q8BMS2, Q8C255

Diamond homologs: O75629, O88668, Q5ZJ73, Q8BGC9, Q8IUH2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

691 predictions. Top by Δscore:

Variant	Effect	Δscore
2:101355362:TTTTT:T	acceptor_gain	1.0000
2:101355364:TTT:T	acceptor_gain	1.0000
2:101355365:TT:T	acceptor_gain	1.0000
2:101355366:TC:T	acceptor_loss	1.0000
2:101355367:C:CC	acceptor_gain	1.0000
2:101355368:T:A	acceptor_loss	1.0000
2:101355371:A:AC	acceptor_gain	1.0000
2:101355371:A:C	acceptor_gain	1.0000
2:101355373:G:C	acceptor_gain	1.0000
2:101355373:G:GC	acceptor_gain	1.0000
2:101383544:C:A	donor_gain	1.0000
2:101387012:CTCA:C	donor_loss	1.0000
2:101387013:TCA:T	donor_loss	1.0000
2:101387014:CACCT:C	donor_loss	1.0000
2:101387015:A:C	donor_loss	1.0000
2:101387016:C:CA	donor_loss	1.0000
2:101387016:CCTT:C	donor_gain	1.0000
2:101355250:CACCT:C	donor_loss	0.9900
2:101355251:A:T	donor_loss	0.9900
2:101355363:TTTT:T	acceptor_gain	0.9900
2:101355370:CATG:C	acceptor_gain	0.9900
2:101383543:C:CA	donor_gain	0.9900
2:101387011:GCTCA:G	donor_loss	0.9900
2:101350917:A:AC	donor_gain	0.9800
2:101350918:C:CC	donor_gain	0.9800
2:101355286:T:TA	donor_gain	0.9800
2:101383494:T:TA	donor_gain	0.9800
2:101383495:C:A	donor_gain	0.9800
2:101387015:A:AC	donor_gain	0.9800
2:101387016:C:CC	donor_gain	0.9800

AlphaMissense

1885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:101355274:G:T	A235D	0.980
2:101383664:A:C	S160R	0.980
2:101383664:A:T	S160R	0.980
2:101383666:T:G	S160R	0.980
2:101350951:T:C	Y282C	0.975
2:101350952:A:G	Y282H	0.975
2:101350951:T:G	Y282S	0.969
2:101383643:G:C	S167R	0.969
2:101383643:G:T	S167R	0.969
2:101383645:T:G	S167R	0.969
2:101383639:C:A	G169W	0.963
2:101355258:A:C	F240L	0.961
2:101355258:A:T	F240L	0.961
2:101355260:A:G	F240L	0.961
2:101355319:A:G	L220P	0.960
2:101387338:C:A	W40C	0.959
2:101387338:C:G	W40C	0.959
2:101387146:G:C	F104L	0.958
2:101387146:G:T	F104L	0.958
2:101387148:A:G	F104L	0.958
2:101387078:G:T	A127D	0.955
2:101387076:G:T	R128S	0.951
2:101350952:A:C	Y282D	0.949
2:101355313:C:T	G222D	0.948
2:101383638:C:T	G169E	0.948
2:101351017:A:C	M260R	0.947
2:101355266:C:G	A238P	0.947
2:101383638:C:A	G169V	0.946
2:101383590:A:G	L185P	0.943
2:101383659:C:T	G162D	0.943

dbSNP variants (sampled 300 via entrez): RS1000097793 (2:101380443 G>A), RS1000189762 (2:101388921 T>C), RS1000233492 (2:101366903 G>C,T), RS1000283281 (2:101388614 T>A), RS1000326605 (2:101347331 T>C), RS1000337587 (2:101360482 C>T), RS1000475835 (2:101377098 T>C), RS1000491711 (2:101353970 G>C,T), RS1000572323 (2:101347536 T>C), RS1000575924 (2:101370330 T>C), RS1000736302 (2:101364809 G>A,C), RS1000743007 (2:101384215 C>A), RS1000771074 (2:101382876 G>A), RS1000913616 (2:101365020 G>A), RS1000962502 (2:101352461 A>T)

Disease associations

OMIM: gene MIM:618540 | 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
GCST003095_4	Adiponectin levels (BMI-adjusted)	2.000000e-06
GCST003096_3	Adiponectin levels	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007737	BMI-adjusted adiponectin measurement
EFO:0004502	adiponectin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, decreases expression	1
urushiol	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	decreases expression	1
2-tert-butylhydroquinone	affects response to substance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
pentanal	increases expression	1
avobenzone	increases expression	1
dinophysistoxin 1	decreases expression	1
abrine	decreases expression	1
NSC 689534	affects binding, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	affects expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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