RGSL1

Summary

RGSL1 (regulator of G protein signaling like 1, HGNC:18636) is a protein-coding gene on chromosome 1q25.3, encoding Regulator of G-protein signaling protein-like (A5PLK6).

Predicted to be located in membrane.

Source: NCBI Gene 353299 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 168 total
• MANE Select transcript: NM_001137669

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18636
Approved symbol	RGSL1
Name	regulator of G protein signaling like 1
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000121446
Ensembl biotype	protein_coding
OMIM	611012
Entrez	353299

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 8 protein_coding, 6 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000294854, ENST00000367561, ENST00000415960, ENST00000416676, ENST00000422241, ENST00000426890, ENST00000427189, ENST00000436031, ENST00000437548, ENST00000443996, ENST00000444367, ENST00000447374, ENST00000456971, ENST00000634342, ENST00000634626, ENST00000634679, ENST00000634723, ENST00000634758, ENST00000634801, ENST00000635407, ENST00000635539, ENST00000648414

RefSeq mRNA: 2 — MANE Select: NM_001137669 NM_001137669, NM_001366934

CCDS: CCDS58049

Canonical transcript exons

ENST00000294854 — 22 exons

Exon	Start	End
ENSE00002342422	182488980	182489202
ENSE00002606110	182450146	182450178
ENSE00003468888	182553455	182553541
ENSE00003495994	182458319	182458393
ENSE00003498764	182551100	182551209
ENSE00003507074	182530244	182530361
ENSE00003511615	182548317	182548455
ENSE00003523613	182548700	182548824
ENSE00003534828	182472396	182472557
ENSE00003545570	182556024	182556222
ENSE00003571805	182488285	182488347
ENSE00003591040	182493022	182493129
ENSE00003598910	182554627	182554693
ENSE00003603675	182453958	182454040
ENSE00003614882	182527579	182527772
ENSE00003614898	182540247	182540421
ENSE00003621365	182473575	182474542
ENSE00003641397	182532662	182532791
ENSE00003670089	182522004	182522109
ENSE00003683257	182530790	182530910
ENSE00003692856	182460004	182460133
ENSE00003850188	182560279	182560597

Expression profiles

Bgee: expression breadth broad, 84 present calls, max score 88.64.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0183 / max 20.7499, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7041	0.0183	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	88.64	gold quality
type B pancreatic cell	CL:0000169	88.32	gold quality
olfactory bulb	UBERON:0002264	87.32	gold quality
tongue squamous epithelium	UBERON:0006919	87.17	gold quality
left testis	UBERON:0004533	83.49	gold quality
right testis	UBERON:0004534	83.16	gold quality
male germ cell	CL:0000015	81.50	silver quality
testis	UBERON:0000473	80.83	gold quality
sperm	CL:0000019	80.74	silver quality
thymus	UBERON:0002370	77.79	gold quality
diaphragm	UBERON:0001103	77.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.16	gold quality
upper arm skin	UBERON:0004263	76.82	gold quality
cervix epithelium	UBERON:0004801	75.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.97	gold quality
orbitofrontal cortex	UBERON:0004167	74.03	gold quality
epithelium of nasopharynx	UBERON:0001951	73.87	gold quality
hair follicle	UBERON:0002073	73.31	gold quality
CA1 field of hippocampus	UBERON:0003881	72.98	gold quality
epithelial cell of pancreas	CL:0000083	72.82	gold quality
mucosa of urinary bladder	UBERON:0001259	72.69	gold quality
layer of synovial tissue	UBERON:0007616	72.41	gold quality
cardia of stomach	UBERON:0001162	72.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	72.08	gold quality
dorsal plus ventral thalamus	UBERON:0001897	72.04	gold quality
pharyngeal mucosa	UBERON:0000355	71.62	gold quality
trachea	UBERON:0003126	71.53	gold quality
subthalamic nucleus	UBERON:0001906	71.51	gold quality
ventral tegmental area	UBERON:0002691	71.46	gold quality
vastus lateralis	UBERON:0001379	71.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.28

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• A detailed mapping of the breakpoints revealed intragenic microdeletions affecting the coding regions of RGSL2, RGSL1. (PMID:18521847)
• Missense mutations in RGSL1 gene is associated with breast cancer. (PMID:21135262)
• Data indicate that multiplex ligation-dependent probe amplification (MLPA) probes (Fig. 2) corresponding to the RGSL2, RGSL1 and RGS16 genes showed 64.5 % tumour samples with copy number gains and 5 % tumour samples with copy number losses. (PMID:23248035)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rgsl1	ENSMUSG00000042641
rattus_norvegicus	Rgsl1	ENSRNOG00000026952

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGS13 (ENSG00000127074), RGS22 (ENSG00000132554), RGS8 (ENSG00000135824), RGS3 (ENSG00000138835), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling protein-like — A5PLK6 (reviewed: A5PLK6)

All UniProt accessions (14): A0A0U1RQD8, A0A0U1RRA3, A0A0U1RRF3, A0A0U1RRF6, A0A0U1RRG0, A0A0U1RRN0, A0A3B3ISC9, A5PLK6, H3BNQ0, H3BNR3, H3BNS3, H3BRN5, H3BU64, H3BVE8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (6)

UniProt ID	Names	Canonical?
A5PLK6-1	1	yes
A5PLK6-2	2
A5PLK6-3	3
A5PLK6-4	4
A5PLK6-5	5
A5PLK6-6	6

RefSeq proteins (2): NP_001131141, NP_001353863 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016137	RGS	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR044926	RGS_subdomain_2	Homologous_superfamily
IPR053282	RGS_domain-containing	Family

Pfam: PF00615

UniProt features (17 total): splice variant 8, sequence variant 2, sequence conflict 2, chain 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A5PLK6-F1	67.79	0.08

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-418597	G alpha (z) signalling events

MSigDB gene sets: 34 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, REACTOME_G_ALPHA_Z_SIGNALLING_EVENTS, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, WTGAAAT_UNKNOWN, YY1_01, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, QI_PLASMACYTOMA_DN, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_UP, chr1q25, CTIP_DN.V1_UP, MIR4700_5P, MIR6129, MIR4510, MIR6130, MIR4667_5P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGSL1	TEX35	Q5T0J7	896
RGSL1	RALGPS2	Q86X27	842
RGSL1	RGS8	P57771	792
RGSL1	RGS16	O15492	792
RGSL1	RGS13	O14921	777
RGSL1	RGS17	Q9UGC6	776
RGSL1	RGS18	Q9NS28	776
RGSL1	RGS20	O76081	771
RGSL1	RGS21	Q2M5E4	771
RGSL1	RGS5	O15539	764
RGSL1	RGS6	P49758	761
RGSL1	RGS10	O43665	759
RGSL1	RGS12	O14924	758
RGSL1	RGS11	O94810	756
RGSL1	RGS19	P49795	746

IntAct

3 interactions, top by confidence:

A	B	Type	Score
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350

BioGRID (9): RGSL1 (Two-hybrid), RGSL1 (Synthetic Lethality), MAGT1 (Proximity Label-MS), RGSL1 (Affinity Capture-RNA), D2HGDH (Co-fractionation), REXO2 (Co-fractionation), RGSL1 (Cross-Linking-MS (XL-MS)), RGSL1 (Cross-Linking-MS (XL-MS)), RGSL1 (Affinity Capture-MS)

ESM2 similar proteins: A2RRS8, A4D1B5, A5PLK6, D3Z6S9, E7FA21, G3UYX5, O75747, O75901, O88480, O88869, Q2T9P0, Q3UMB5, Q3UPC7, Q3URV1, Q402B2, Q4R9E9, Q5SUS0, Q5T0N1, Q5XI56, Q5XX13, Q642P2, Q6DHV5, Q6INI0, Q6P2C0, Q7L0X2, Q80X60, Q86VV8, Q86WZ0, Q8CDN1, Q8IV33, Q8IXR9, Q8K342, Q8N7B9, Q8N7X0, Q8ND61, Q8NE09, Q8NG48, Q8R4Y8, Q8TDY2, Q8TEV9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	148
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3743 predictions. Top by Δscore:

Variant	Effect	Δscore
1:182472461:G:GT	donor_gain	1.0000
1:182472518:G:GT	donor_gain	1.0000
1:182472519:A:T	donor_gain	1.0000
1:182472528:GGGTG:G	donor_gain	1.0000
1:182472529:GGTGG:G	donor_gain	1.0000
1:182472530:G:T	donor_gain	1.0000
1:182472558:G:GG	donor_gain	1.0000
1:182530235:A:AG	acceptor_gain	1.0000
1:182530236:T:G	acceptor_gain	1.0000
1:182530239:TCTA:T	acceptor_loss	1.0000
1:182530240:CTA:C	acceptor_loss	1.0000
1:182530241:TA:T	acceptor_loss	1.0000
1:182530242:A:AG	acceptor_gain	1.0000
1:182530243:G:GT	acceptor_gain	1.0000
1:182530243:GA:G	acceptor_gain	1.0000
1:182530243:GAA:G	acceptor_gain	1.0000
1:182530243:GAAGA:G	acceptor_gain	1.0000
1:182530358:AGTGG:A	donor_loss	1.0000
1:182530359:GTG:G	donor_gain	1.0000
1:182530360:TGG:T	donor_loss	1.0000
1:182530362:G:A	donor_loss	1.0000
1:182530362:G:GG	donor_gain	1.0000
1:182530363:T:G	donor_loss	1.0000
1:182530364:GA:G	donor_loss	1.0000
1:182530365:AGTAT:A	donor_loss	1.0000
1:182532657:CCCA:C	acceptor_loss	1.0000
1:182532658:CCA:C	acceptor_loss	1.0000
1:182532660:A:AG	acceptor_gain	1.0000
1:182532660:AGA:A	acceptor_loss	1.0000
1:182532661:G:GA	acceptor_loss	1.0000

AlphaMissense

7239 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:182548817:T:A	W976R	0.995
1:182548817:T:C	W976R	0.995
1:182540346:G:C	R865P	0.994
1:182458361:T:A	W47R	0.992
1:182458361:T:C	W47R	0.992
1:182548705:T:A	N938K	0.992
1:182548705:T:G	N938K	0.992
1:182532762:T:C	L822P	0.989
1:182548401:A:C	K918N	0.989
1:182548401:A:T	K918N	0.989
1:182540393:G:C	D881H	0.988
1:182540345:C:A	R865S	0.987
1:182540394:A:C	D881A	0.987
1:182548400:A:T	K918I	0.987
1:182551101:T:C	F979L	0.987
1:182551103:T:A	F979L	0.987
1:182551103:T:G	F979L	0.987
1:182460031:T:A	W67R	0.986
1:182460031:T:C	W67R	0.986
1:182548423:T:C	F926L	0.986
1:182548425:C:A	F926L	0.986
1:182548425:C:G	F926L	0.986
1:182527668:T:C	F674S	0.984
1:182527631:T:C	F662L	0.983
1:182527633:C:A	F662L	0.983
1:182527633:C:G	F662L	0.983
1:182532710:T:G	Y805D	0.983
1:182548819:G:C	W976C	0.983
1:182548819:G:T	W976C	0.983
1:182540394:A:G	D881G	0.982

dbSNP variants (sampled 300 via entrez): RS1000031543 (1:182457333 C>T), RS1000066014 (1:182516014 A>G), RS1000080951 (1:182470135 C>G), RS1000104361 (1:182495773 C>A), RS1000145100 (1:182516270 G>A), RS1000150027 (1:182463957 T>A,C), RS1000153332 (1:182493677 ATGTGAATGCCCC>A), RS1000165282 (1:182482493 A>C), RS1000262155 (1:182482130 A>G), RS1000310684 (1:182540880 T>C,G), RS1000346552 (1:182451687 T>C), RS1000381442 (1:182534599 C>T), RS1000408333 (1:182484223 T>C), RS1000429942 (1:182508682 T>G), RS1000456035 (1:182491214 AATT>A,AATTATT)

Disease associations

OMIM: gene MIM:611012 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005183_7	Common carotid intima-media thickness	3.000000e-06
GCST007565_112	Morning person	7.000000e-30
GCST011359_19	Venous thromboembolism	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
fluorene-9-bisphenol	increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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