CGRRF1

Summary

CGRRF1 (cell growth regulator with ring finger domain 1, HGNC:15528) is a protein-coding gene on chromosome 14q22.2, encoding Cell growth regulator with RING finger domain protein 1 (Q99675). Able to inhibit growth in several cell lines.

Predicted to enable zinc ion binding activity. Predicted to be involved in negative regulation of cell growth. Located in endoplasmic reticulum and nucleoplasm.

Source: NCBI Gene 10668 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_006568

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15528
Approved symbol	CGRRF1
Name	cell growth regulator with ring finger domain 1
Location	14q22.2
Locus type	gene with protein product
Status	Approved
Aliases	CGR19, RNF197
Ensembl gene	ENSG00000100532
Ensembl biotype	protein_coding
OMIM	606138
Entrez	10668

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000216420, ENST00000554791, ENST00000556172, ENST00000556216, ENST00000557184, ENST00000557317, ENST00000557429, ENST00000557512, ENST00000557755, ENST00000679442, ENST00000679557, ENST00000908184, ENST00000908185, ENST00000939686, ENST00000939687

RefSeq mRNA: 1 — MANE Select: NM_006568 NM_006568

CCDS: CCDS9719

Canonical transcript exons

ENST00000216420 — 6 exons

Exon	Start	End
ENSE00000854783	54509906	54510063
ENSE00003460123	54530049	54530226
ENSE00003562564	54530903	54531050
ENSE00003656025	54522454	54522593
ENSE00003679397	54537722	54537829
ENSE00003969512	54538063	54539292

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 92.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1319 / max 217.0966, expressed in 1744 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139640	11.5132	1739
139639	0.6187	319

Top tissues by expression

299 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	92.79	gold quality
right testis	UBERON:0004534	91.45	gold quality
left testis	UBERON:0004533	91.26	gold quality
islet of Langerhans	UBERON:0000006	91.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.13	gold quality
testis	UBERON:0000473	90.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.37	gold quality
gastrocnemius	UBERON:0001388	89.57	gold quality
muscle of leg	UBERON:0001383	89.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.24	gold quality
triceps brachii	UBERON:0001509	89.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.93	gold quality
prefrontal cortex	UBERON:0000451	88.85	gold quality
calcaneal tendon	UBERON:0003701	88.81	gold quality
putamen	UBERON:0001874	88.66	gold quality
gluteal muscle	UBERON:0002000	88.54	gold quality
muscle organ	UBERON:0001630	88.50	gold quality
skeletal muscle organ	UBERON:0014892	88.50	gold quality
spinal cord	UBERON:0002240	88.07	gold quality
nucleus accumbens	UBERON:0001882	88.03	gold quality
caudate nucleus	UBERON:0001873	87.79	gold quality
amygdala	UBERON:0001876	87.77	gold quality
cingulate cortex	UBERON:0003027	87.55	gold quality
right frontal lobe	UBERON:0002810	87.46	gold quality
anterior cingulate cortex	UBERON:0009835	87.46	gold quality
cerebellar cortex	UBERON:0002129	87.37	gold quality
adenohypophysis	UBERON:0002196	87.37	gold quality
cerebellar hemisphere	UBERON:0002245	87.36	gold quality
diaphragm	UBERON:0001103	87.34	gold quality
apex of heart	UBERON:0002098	87.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SUPT20H

miRNA regulators (miRDB)

19 targeting CGRRF1, 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-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-376A-2-5P	96.43	68.06	715
HSA-MIR-624-5P	96.00	68.88	728

Literature-anchored findings (GeneRIF, showing 3)

• Novel transcription factors identified in human CD34 antigen-positive hematopoietic stem cells. (PMID:12070015)
• CGRRF1 represents a novel, reproducible tissue marker of metformin response in the obese endometrium and our preliminary data suggests that up-regulation of CGRRF1 expression may prove clinically useful in the prevention or treatment of endometrial cancer (PMID:24680596)
• We demonstrate that CGRRF1 suppresses growth of breast cancer and its E3 ligase activity is involved in CGRRF1-mediated growth suppression. (PMID:31801577)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cgrrf1	ENSDARG00000037040
mus_musculus	Cgrrf1	ENSMUSG00000055128
rattus_norvegicus	Cgrrf1	ENSRNOG00000010178

Protein

Protein identifiers

Cell growth regulator with RING finger domain protein 1 — Q99675 (reviewed: Q99675)

Alternative names: Cell growth regulatory gene 19 protein, RING finger protein 197

All UniProt accessions (7): Q99675, A0A7P0Z480, A0A7P0Z4Q1, G3V229, G3V2K9, G3V412, M0QZQ7

UniProt curated annotations — full annotation on UniProt →

Function. Able to inhibit growth in several cell lines.

Subcellular location. Nucleus. Endoplasmic reticulum.

Tissue specificity. Ubiquitously expressed with high expression in testis and the cerebellum.

Induction. Up-regulated by endoplasmic reticulum (ER) stress triggered by thapsigargin or tunicamycin.

RefSeq proteins (1): NP_006559* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR042496	CGRF1	Family

Pfam: PF13920

UniProt features (8 total): turn 2, chain 1, zinc finger region 1, sequence variant 1, sequence conflict 1, strand 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EA5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99675-F1	80.37	0.57

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 100 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, BROWNE_HCMV_INFECTION_12HR_UP, GOBP_REGULATION_OF_CELL_CYCLE, PEART_HDAC_PROLIFERATION_CLUSTER_UP, SCHLOSSER_SERUM_RESPONSE_DN, AACTTT_UNKNOWN, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, BROWNE_HCMV_INFECTION_10HR_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_CELL_GROWTH, GOBP_REGULATION_OF_GROWTH, GRYDER_PAX3FOXO1_TOP_ENHANCERS

GO Biological Process (3): negative regulation of cell population proliferation (GO:0008285), negative regulation of cell growth (GO:0030308), regulation of cell cycle (GO:0051726)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cellular process	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
cell population proliferation	1
regulation of cell population proliferation	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
cell cycle	1
regulation of cellular process	1
transition metal ion binding	1
binding	1
cation binding	1
nuclear lumen	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CGRRF1	CGREF1	Q99674	960
CGRRF1	UBE2J2	Q8N2K1	602
CGRRF1	RNFT1	Q5M7Z0	584
CGRRF1	RNF170	Q96K19	512
CGRRF1	CNIH1	O95406	507
CGRRF1	FAM8A1	Q9UBU6	487
CGRRF1	SEL1L	Q9UBV2	475
CGRRF1	GMFB	P17774	464
CGRRF1	RNF26	Q9BY78	447
CGRRF1	TP53	P04637	446
CGRRF1	UBE2J1	Q9Y385	433
CGRRF1	RNF145	Q96MT1	420
CGRRF1	RNF130	Q86XS8	416
CGRRF1	MARCHF6	O60337	413
CGRRF1	RNFT2	Q96EX2	413

IntAct

138 interactions, top by confidence:

A	B	Type	Score
CGRRF1	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
CD72	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
SLC30A3	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
BET1	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
AGR3	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
TMEM187	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
LAPTM4B	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
CDIPT	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
TMEM140	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
TMEM97	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
SCAMP4	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
YIPF6	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
LNPEP	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
CGRRF1	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
CYB5B	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560
MARCHF5	CGRRF1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (148): CGRRF1 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), KIDINS220 (Affinity Capture-MS), SREBF2 (Affinity Capture-MS), POM121 (Affinity Capture-MS), CYP51A1 (Affinity Capture-MS), ALG13 (Affinity Capture-MS), KIAA0922 (Affinity Capture-MS), PLEKHB2 (Affinity Capture-MS), FOXD2 (Affinity Capture-MS), USP33 (Affinity Capture-MS), GLG1 (Affinity Capture-MS)

ESM2 similar proteins: A4IG66, B0DOB4, B1WC10, O15327, O76024, O88480, P56695, P97587, Q01H84, Q08D69, Q0IJ20, Q1T765, Q3B8G8, Q499Q5, Q4QQM5, Q4R4D7, Q566H4, Q5BIY5, Q5RA60, Q5SW19, Q5SW45, Q5U1Z0, Q5U249, Q5U2W4, Q5XHA1, Q5XJS0, Q642Q3, Q6GR21, Q6PFL0, Q6Q7J5, Q7SZC5, Q7ZWF4, Q8BMG7, Q8BMJ7, Q8C456, Q8CJF7, Q8N3R3, Q8NAN2, Q8VDY4, Q8WYP5

Diamond homologs: P97587, Q8BMJ7, Q8BUH7, Q99675, Q9BY78, A8MQ27, O76050, Q05A36, Q0MW30, Q24746, Q3TEL6, Q3UE17, Q5M870, Q5NCX5, Q5U5Q3, Q7M3S9, Q84ME1, Q8CJC5, Q8LA32, Q923S6, Q96EH8, Q96PX1, Q9BR09, Q9D0S4, Q9FPH0, Q9LYW5, M0R5D6, O60291, Q5XIQ4, Q6INH1, Q7ZUL9, Q9D074, Q9LFH6, Q9S752, A8JAM0, A9JTP3, D3ZDI6, D3ZN95, P15258, P51610

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	CGRRF1	ubiquitination
CGRRF1	“down-regulates quantity by destabilization”	EGFR	polyubiquitination

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	35
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1471 predictions. Top by Δscore:

Variant	Effect	Δscore
14:54510059:GGATG:G	donor_gain	1.0000
14:54510060:GATG:G	donor_gain	1.0000
14:54510060:GATGG:G	donor_gain	1.0000
14:54510062:TGGT:T	donor_loss	1.0000
14:54510063:GGTA:G	donor_loss	1.0000
14:54510065:TAAGT:T	donor_loss	1.0000
14:54522594:G:GG	donor_gain	1.0000
14:54530216:G:GT	donor_gain	1.0000
14:54530217:A:T	donor_gain	1.0000
14:54538057:TTTCA:T	acceptor_loss	1.0000
14:54538058:TTCA:T	acceptor_loss	1.0000
14:54538059:TCAG:T	acceptor_loss	1.0000
14:54538060:CAGCA:C	acceptor_loss	1.0000
14:54538061:A:AG	acceptor_gain	1.0000
14:54538061:AGC:A	acceptor_loss	1.0000
14:54538062:G:GG	acceptor_gain	1.0000
14:54538062:GC:G	acceptor_gain	1.0000
14:54538062:GCA:G	acceptor_gain	1.0000
14:54538062:GCAA:G	acceptor_gain	1.0000
14:54538105:A:AG	acceptor_gain	1.0000
14:54510064:G:GG	donor_gain	0.9900
14:54522540:TC:T	donor_gain	0.9900
14:54529967:G:GT	donor_gain	0.9900
14:54530196:AT:A	donor_gain	0.9900
14:54530203:A:G	donor_gain	0.9900
14:54530223:ATT:A	donor_gain	0.9900
14:54530224:TTT:T	donor_gain	0.9900
14:54530865:T:TA	acceptor_gain	0.9900
14:54530872:A:AG	acceptor_gain	0.9900
14:54530873:G:GG	acceptor_gain	0.9900

AlphaMissense

2191 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:54538204:T:A	C274S	0.999
14:54538204:T:C	C274R	0.999
14:54538205:G:A	C274Y	0.999
14:54538205:G:C	C274S	0.999
14:54538206:T:G	C274W	0.999
14:54538213:T:C	C277R	0.999
14:54538249:T:C	C289R	0.999
14:54538257:C:A	H291Q	0.999
14:54538257:C:G	H291Q	0.999
14:54538267:T:C	C295R	0.999
14:54538276:T:C	C298R	0.999
14:54538297:T:C	C305R	0.999
14:54538306:T:C	C308R	0.999
14:54538310:G:C	R309T	0.999
14:54538310:G:T	R309M	0.999
14:54510029:T:C	C24R	0.998
14:54538211:T:A	V276D	0.998
14:54538213:T:A	C277S	0.998
14:54538214:G:C	C277S	0.998
14:54538250:G:A	C289Y	0.998
14:54538253:G:C	R290T	0.998
14:54538253:G:T	R290I	0.998
14:54538255:C:G	H291D	0.998
14:54538268:G:A	C295Y	0.998
14:54538297:T:A	C305S	0.998
14:54538298:G:C	C305S	0.998
14:54538299:C:G	C305W	0.998
14:54538306:T:A	C308S	0.998
14:54538307:G:C	C308S	0.998
14:54538311:G:C	R309S	0.998

dbSNP variants (sampled 300 via entrez): RS1000008891 (14:54521219 G>C,T), RS1000216724 (14:54514836 C>A), RS1000299173 (14:54527369 A>T), RS1000467493 (14:54535684 C>A,G,T), RS1000487878 (14:54509278 C>G), RS1000498434 (14:54515929 T>C), RS1000540834 (14:54536004 A>T), RS1000571982 (14:54536347 C>T), RS1001018965 (14:54517915 G>A), RS1001074543 (14:54534249 C>T), RS1001099435 (14:54529865 G>A), RS1001183564 (14:54533484 G>A,C), RS1001193492 (14:54533592 T>C), RS1001646411 (14:54533817 A>C,G), RS1001686241 (14:54514982 G>C)

Disease associations

OMIM: gene MIM:606138 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001786_22	Dental caries	2.000000e-07
GCST001786_33	Dental caries	2.000000e-06
GCST003477_3	Monobrow thickness	4.000000e-07
GCST003542_167	Night sleep phenotypes	2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Cyclosporine	increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	increases expression	1
NSC 689534	affects binding, increases expression	1
Gefitinib	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Gold	decreases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation, increases expression	1

Clinical trials (associated diseases)

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