RERGL

Summary

RERGL (RERG like, HGNC:26213) is a protein-coding gene on chromosome 12p12.3, encoding Ras-related and estrogen-regulated growth inhibitor-like protein (Q9H628). Binds GDP/GTP and may possess intrinsic GTPase activity.

Predicted to enable G protein activity and GTP binding activity.

Source: NCBI Gene 79785 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001286201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26213
Approved symbol	RERGL
Name	RERG like
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22655
Ensembl gene	ENSG00000111404
Ensembl biotype	protein_coding
Entrez	79785

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000229002, ENST00000536890, ENST00000538724, ENST00000540148, ENST00000541632

RefSeq mRNA: 2 — MANE Select: NM_001286201 NM_001286201, NM_024730

CCDS: CCDS66332, CCDS8679

Canonical transcript exons

ENST00000538724 — 5 exons

Exon	Start	End
ENSE00000999929	18090089	18090193
ENSE00002276899	18080869	18081473
ENSE00003486726	18084517	18084665
ENSE00003551786	18088900	18088956
ENSE00003648401	18085620	18085693

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 96.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5734 / max 154.4339, expressed in 146 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129996	0.3720	126
129995	0.1147	55
129994	0.0640	37
129993	0.0227	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	96.19	gold quality
tibial artery	UBERON:0007610	96.19	gold quality
blood vessel layer	UBERON:0004797	95.20	gold quality
artery	UBERON:0001637	94.94	gold quality
calcaneal tendon	UBERON:0003701	92.06	gold quality
left uterine tube	UBERON:0001303	88.96	gold quality
body of uterus	UBERON:0009853	88.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.51	gold quality
left coronary artery	UBERON:0001626	88.31	gold quality
aorta	UBERON:0000947	87.99	gold quality
right coronary artery	UBERON:0001625	87.70	gold quality
coronary artery	UBERON:0001621	86.79	gold quality
endocervix	UBERON:0000458	86.30	gold quality
rectum	UBERON:0001052	85.31	gold quality
omental fat pad	UBERON:0010414	85.03	gold quality
peritoneum	UBERON:0002358	84.95	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.29	gold quality
nerve	UBERON:0001021	84.02	gold quality
tibial nerve	UBERON:0001323	84.02	gold quality
superficial temporal artery	UBERON:0001614	83.43	gold quality
metanephros cortex	UBERON:0010533	83.43	gold quality
adipose tissue	UBERON:0001013	82.64	gold quality
mucosa of stomach	UBERON:0001199	82.48	gold quality
parietal pleura	UBERON:0002400	82.15	gold quality
gall bladder	UBERON:0002110	82.10	gold quality
connective tissue	UBERON:0002384	82.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.29	gold quality
tendon	UBERON:0000043	80.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	61.80
E-MTAB-8410	yes	24.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting RERGL, 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-574-5P	100.00	66.01	989
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AN	99.97	70.91	2817
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-96-3P	97.47	68.03	839
HSA-MIR-5192	96.89	63.35	879
HSA-MIR-203A-5P	96.33	65.03	714
HSA-MIR-3622B-5P	94.62	64.58	835
HSA-MIR-6084	89.09	62.33	58

Literature-anchored findings (GeneRIF, showing 1)

• Loss of RERGL expression is associated with familial colorectal cancer. (PMID:24127187)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rergla	ENSDARG00000019396
mus_musculus	Rergl	ENSMUSG00000092164
rattus_norvegicus	Rergl	ENSRNOG00000008130

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RAP2A (ENSG00000125249), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), RERG (ENSG00000134533), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RALB (ENSG00000144118), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), DIRAS3 (ENSG00000162595), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RRAD (ENSG00000166592), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

Protein

Protein identifiers

Ras-related and estrogen-regulated growth inhibitor-like protein — Q9H628 (reviewed: Q9H628)

Alternative names: RERG/Ras-like protein

All UniProt accessions (3): Q9H628, F5H686, G5EA41

UniProt curated annotations — full annotation on UniProt →

Function. Binds GDP/GTP and may possess intrinsic GTPase activity.

Similarity. Belongs to the small GTPase superfamily. Ras family.

RefSeq proteins (2): NP_001273130, NP_079006 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR051065	Ras-related_GTPase	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (6 total): binding site 3, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H628-F1	77.18	0.38

Functional residue map

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

Ligand- & substrate-binding residues (3): 11–18; 58–64; 123–126

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): DELYS_THYROID_CANCER_DN, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, BOQUEST_STEM_CELL_UP, chr12p12, VERHAAK_GLIOBLASTOMA_NEURAL, HES2_TARGET_GENES, SALL4_TARGET_GENES, UBN1_TARGET_GENES, ZNF22_TARGET_GENES, LET_7C_3P, MIR6817_3P, MIR5689, MIR2681_5P, MIR1257

GO Biological Process (0):

GO Molecular Function (5): G protein activity (GO:0003925), GTP binding (GO:0005525), nucleotide binding (GO:0000166), GTPase activity (GO:0003924), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ribonucleoside triphosphate phosphatase activity	1
catalytic activity	1

Protein interactions and networks

STRING

1711 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RERGL	PIK3C2G	O75747	418
RERGL	TMEM74B	Q9NUR3	411
RERGL	FLYWCH1	Q4VC44	400
RERGL	MAP3K7CL	P57077	389
RERGL	CFAP58	Q5T655	367
RERGL	C10orf53	Q8N6V4	358
RERGL	MOSPD1	Q9UJG1	353
RERGL	VGLL3	A8MV65	345
RERGL	NKIRAS1	Q9NYS0	330
RERGL	OSBPL3	Q9H4L5	326
RERGL	NANOS2	P60321	303
RERGL	KBTBD12	Q3ZCT8	302
RERGL	PLEKHA5	Q9HAU0	293
RERGL	GSG1L	Q6UXU4	292
RERGL	EBPL	Q9BY08	288

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A1DZY4, A6QP66, O35626, O35929, O88910, O88954, P0C0E4, P35295, P51157, P51158, P53667, P53668, P53669, P55040, P55041, P55043, P63032, P63033, Q06AU5, Q12829, Q13368, Q13637, Q3SWY9, Q5E9J3, Q5FVY2, Q5R541, Q5RFI2, Q6DGN0, Q6IMA3, Q6IMA7, Q6IMB1, Q6P0U3, Q6T310, Q8AVS6, Q8IYK8, Q8QFP8, Q8VEL9, Q8VHP8, Q8VHQ4, Q8WXH6

Diamond homologs: A1DZY4, A6QP66, A8NU18, C4YKT4, O08989, O14807, O35929, O88667, O93856, O94363, P01119, P03967, P08645, P08647, P0CY32, P10114, P10536, P11233, P11234, P15064, P17609, P22124, P22126, P22278, P22279, P22280, P28775, P32254, P36860, P36863, P48555, P59279, P61105, P61225, P61226, P61227, P62070, P62071, P63320, P63321

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1506 predictions. Top by Δscore:

Variant	Effect	Δscore
12:18081469:CAGCT:C	acceptor_gain	1.0000
12:18081472:CT:C	acceptor_gain	1.0000
12:18081473:TCTG:T	acceptor_loss	1.0000
12:18081474:C:CC	acceptor_gain	1.0000
12:18081474:CTG:C	acceptor_loss	1.0000
12:18081475:T:A	acceptor_loss	1.0000
12:18084566:T:TC	acceptor_gain	1.0000
12:18293899:A:AG	acceptor_gain	1.0000
12:18293900:G:GG	acceptor_gain	1.0000
12:18293900:GCT:G	acceptor_gain	1.0000
12:18293900:GCTA:G	acceptor_gain	1.0000
12:18294011:CAAAA:C	donor_gain	1.0000
12:18294012:AAAA:A	donor_gain	1.0000
12:18294013:AAA:A	donor_gain	1.0000
12:18294013:AAAGT:A	donor_loss	1.0000
12:18294014:AA:A	donor_gain	1.0000
12:18294015:AG:A	donor_loss	1.0000
12:18294016:G:GG	donor_gain	1.0000
12:18294017:TAA:T	donor_loss	1.0000
12:18081470:AGCT:A	acceptor_gain	0.9900
12:18081479:A:AC	acceptor_gain	0.9900
12:18084511:CCTTA:C	donor_loss	0.9900
12:18084512:CTTA:C	donor_loss	0.9900
12:18084515:A:T	donor_loss	0.9900
12:18084566:T:C	acceptor_gain	0.9900
12:18084666:C:CC	acceptor_gain	0.9900
12:18085611:TTTAC:T	donor_loss	0.9900
12:18085612:TTAC:T	donor_loss	0.9900
12:18085613:TAC:T	donor_loss	0.9900
12:18085614:ACTTA:A	donor_loss	0.9900

AlphaMissense

1339 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:18081438:T:A	K124I	0.999
12:18081437:T:A	K124N	0.998
12:18081437:T:G	K124N	0.998
12:18088925:G:C	F29L	0.998
12:18088925:G:T	F29L	0.998
12:18088927:A:G	F29L	0.998
12:18081447:A:T	V121D	0.996
12:18081397:C:A	G138W	0.994
12:18081429:A:G	L127P	0.994
12:18081438:T:G	K124T	0.994
12:18081444:C:T	G122D	0.994
12:18081362:G:C	F149L	0.993
12:18081362:G:T	F149L	0.993
12:18081364:A:G	F149L	0.993
12:18084610:A:T	V81D	0.993
12:18084616:C:T	G79E	0.993
12:18081411:A:T	V133D	0.992
12:18081439:T:C	K124E	0.992
12:18081450:A:G	L120S	0.992
12:18084602:A:C	Y84D	0.992
12:18088929:C:G	R28P	0.992
12:18088935:G:A	T26I	0.992
12:18088944:C:A	R23M	0.991
12:18081417:C:G	R131P	0.990
12:18081440:G:C	N123K	0.990
12:18081440:G:T	N123K	0.990
12:18081444:C:A	G122V	0.990
12:18081351:G:A	S153F	0.989
12:18081397:C:G	G138R	0.989
12:18081397:C:T	G138R	0.989

dbSNP variants (sampled 300 via entrez): RS1000406392 (12:18086590 T>C), RS1000907824 (12:18082041 G>A), RS1001029037 (12:18083708 A>G), RS1001408371 (12:18088417 C>A), RS1001946489 (12:18083373 G>A), RS1002857463 (12:18081866 T>G), RS1002873756 (12:18090109 C>A,T), RS1002899572 (12:18084806 C>A,G,T), RS1003109528 (12:18091594 T>C), RS1003165368 (12:18086218 A>G), RS1003301706 (12:18091457 T>C), RS1003465848 (12:18091245 C>T), RS1003821357 (12:18091027 T>G), RS1003856911 (12:18086100 C>G), RS1003987602 (12:18086391 C>G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_132	Metabolite levels	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010355	diacylglycerol 36:2 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Cannabidiol	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Aflatoxin B1	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer