GSG1L

Summary

GSG1L (GSG1 like, HGNC:28283) is a protein-coding gene on chromosome 16p12.1, encoding Germ cell-specific gene 1-like protein (Q6UXU4). As a component of the inner core of AMPAR complex, modifies AMPA receptor (AMPAR) gating.

Predicted to be involved in regulation of postsynaptic neurotransmitter receptor internalization. Predicted to act upstream of or within several processes, including regulation of AMPA receptor activity; regulation of short-term neuronal synaptic plasticity; and transmission of nerve impulse. Predicted to be located in asymmetric synapse and membrane. Predicted to be active in Schaffer collateral - CA1 synapse; glutamatergic synapse; and postsynaptic density membrane.

Source: NCBI Gene 146395 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 31 total — 1 pathogenic
• MANE Select transcript: NM_001109763

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28283
Approved symbol	GSG1L
Name	GSG1 like
Location	16p12.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC18079, PRO19651, KTSR5831
Ensembl gene	ENSG00000169181
Ensembl biotype	protein_coding
OMIM	617161
Entrez	146395

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000380897, ENST00000395724, ENST00000447459, ENST00000562611, ENST00000569166, ENST00000898876, ENST00000951030, ENST00000951031

RefSeq mRNA: 4 — MANE Select: NM_001109763 NM_001109763, NM_001323900, NM_001323901, NM_144675

CCDS: CCDS10631, CCDS45450, CCDS81960

Canonical transcript exons

ENST00000447459 — 7 exons

Exon	Start	End
ENSE00001138609	27807487	27807554
ENSE00002598982	27787528	27791467
ENSE00003505418	28063076	28063714
ENSE00003592837	27884486	27884638
ENSE00003639462	27963156	27963203
ENSE00003643759	27828789	27828956
ENSE00003651117	27844950	27845061

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 98.53.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4752 / max 29.6106, expressed in 147 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156857	0.2840	115
156856	0.1550	81
156858	0.0362	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.53	gold quality
pancreatic ductal cell	CL:0002079	85.44	silver quality
right atrium auricular region	UBERON:0006631	85.26	gold quality
putamen	UBERON:0001874	84.46	gold quality
cardiac atrium	UBERON:0002081	84.15	gold quality
nucleus accumbens	UBERON:0001882	83.98	gold quality
caudate nucleus	UBERON:0001873	83.80	gold quality
ascending aorta	UBERON:0001496	82.16	gold quality
thoracic aorta	UBERON:0001515	81.80	gold quality
amygdala	UBERON:0001876	80.70	gold quality
prefrontal cortex	UBERON:0000451	80.69	gold quality
hypothalamus	UBERON:0001898	79.14	gold quality
anterior cingulate cortex	UBERON:0009835	78.00	gold quality
substantia nigra	UBERON:0002038	77.79	gold quality
descending thoracic aorta	UBERON:0002345	76.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.88	silver quality
Brodmann (1909) area 9	UBERON:0013540	75.90	gold quality
midbrain	UBERON:0001891	75.89	gold quality
right frontal lobe	UBERON:0002810	75.43	gold quality
frontal cortex	UBERON:0001870	75.23	gold quality
tendon of biceps brachii	UBERON:0008188	75.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.81	gold quality
neocortex	UBERON:0001950	74.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.69	gold quality
cerebral cortex	UBERON:0000956	72.97	gold quality
forebrain	UBERON:0001890	72.97	gold quality
upper arm skin	UBERON:0004263	72.77	gold quality
temporal lobe	UBERON:0001871	72.66	gold quality
spinal cord	UBERON:0002240	72.49	gold quality
myocardium	UBERON:0002349	72.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

121 targeting GSG1L, 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-1193	100.00	65.93	529
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4658	99.77	64.94	514

Literature-anchored findings (GeneRIF, showing 1)

• gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway (PMID:27010727)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gsg1l	ENSDARG00000037390
mus_musculus	Gsg1l	ENSMUSG00000046182
rattus_norvegicus	Gsg1l	ENSRNOG00000065255

Paralogs (10): LIM2 (ENSG00000105370), NKG7 (ENSG00000105374), PMP22 (ENSG00000109099), GSG1 (ENSG00000111305), EMP1 (ENSG00000134531), EMP3 (ENSG00000142227), CLDND2 (ENSG00000160318), TMEM202 (ENSG00000187806), EMP2 (ENSG00000213853), GSG1L2 (ENSG00000214978)

Protein

Protein identifiers

Germ cell-specific gene 1-like protein — Q6UXU4 (reviewed: Q6UXU4)

All UniProt accessions (2): Q6UXU4, H3BNP0

UniProt curated annotations — full annotation on UniProt →

Function. As a component of the inner core of AMPAR complex, modifies AMPA receptor (AMPAR) gating.

Subunit / interactions. Component of the inner core of AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing.

Subcellular location. Cell membrane. Synapse.

Similarity. Belongs to the GSG1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6UXU4-1	1	yes
Q6UXU4-3	2
Q6UXU4-4	3
Q6UXU4-2	4

RefSeq proteins (4): NP_001103233, NP_001310829, NP_001310830, NP_653276 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012478	GSG-1	Family
IPR050579	PMP-22/EMP/MP20-like	Family

Pfam: PF07803

UniProt features (13 total): topological domain 5, transmembrane region 4, splice variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXU4-F1	72.23	0.35

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 98 (showing top): GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SHORT_TERM_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_RECEPTOR_INTERNALIZATION, GOBP_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_RECEPTOR_INTERNALIZATION, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_TRANSPORT, GOBP_IMPORT_INTO_CELL

GO Biological Process (7): transmission of nerve impulse (GO:0019226), regulation of short-term neuronal synaptic plasticity (GO:0048172), synapse organization (GO:0050808), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), regulation of cell communication (GO:0010646), regulation of signaling (GO:0023051), regulation of transport (GO:0051049)

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

GO Cellular Component (7): plasma membrane (GO:0005886), Schaffer collateral - CA1 synapse (GO:0098685), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), membrane (GO:0016020), asymmetric synapse (GO:0032279), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
synapse	2
postsynaptic density	2
action potential	1
chemical synaptic transmission	1
nervous system process	1
regulation of neuronal synaptic plasticity	1
cell junction organization	1
regulation of receptor internalization	1
regulation of biological quality	1
postsynaptic neurotransmitter receptor internalization	1
regulation of cellular process	1
signaling	1
regulation of biological process	1
transport	1
regulation of localization	1
binding	1
membrane	1
cell periphery	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
cellular anatomical structure	1
neuron to neuron synapse	1
cell junction	1

Protein interactions and networks

STRING

696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSG1L	SHISA9	B4DS77	860
GSG1L	CNIH2	Q6PI25	759
GSG1L	CNIH1	O95406	725
GSG1L	CNIH4	Q9P003	723
GSG1L	GRIA1	P42261	696
GSG1L	SYNDIG1	Q9H7V2	689
GSG1L	CACNG8	Q8WXS5	670
GSG1L	CACNG2	Q9Y698	647
GSG1L	CNIH3	Q8TBE1	646
GSG1L	GRIA2	P42262	541
GSG1L	VWC2	Q2TAL6	527
GSG1L	CCDC196	A0A1B0GTZ2	519
GSG1L	SHISA7	A6NL88	500
GSG1L	FRRS1L	Q9P0K9	490
GSG1L	ABHD6	Q9BV23	458

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GSG1L	LXN	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (2): GSG1L (Two-hybrid), MAL (Two-hybrid)

ESM2 similar proteins: A0JPH4, A4IIV4, A6NGA9, A8MUP6, D3Z7H4, D3ZK93, O42282, O60478, O75204, O95859, P0DP42, P38551, P58418, Q08CE6, Q0II41, Q11085, Q29RH7, Q2KHT4, Q2M2E3, Q32KQ5, Q32LT7, Q3SZT1, Q4V922, Q504G0, Q569A2, Q5CZV0, Q5FWC3, Q5M962, Q5R8B5, Q5RCD5, Q5VW38, Q5XGU1, Q5ZIF5, Q6AXT9, Q6AYL2, Q6GV27, Q6GV28, Q6UXU4, Q7TQI0, Q8BGP5

Diamond homologs: A4IIV4, A8MUP6, D3Z7H4, D3ZK93, Q2KHT4, Q3SZT1, Q4V922, Q6AYL2, Q6UXU4, Q8R1W2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2423570	NC_000016.9:g.(?27441393)(29001333_?)del	Pathogenic

SpliceAI

1536 predictions. Top by Δscore:

Variant	Effect	Δscore
16:27807485:A:AC	donor_gain	1.0000
16:27807486:C:CC	donor_gain	1.0000
16:27807486:CGGG:C	donor_gain	1.0000
16:27807553:TC:T	acceptor_gain	1.0000
16:27807554:CC:C	acceptor_gain	1.0000
16:27844944:ACTTA:A	donor_loss	1.0000
16:27844947:T:TG	donor_loss	1.0000
16:27844948:A:AC	donor_gain	1.0000
16:27844948:ACCAG:A	donor_loss	1.0000
16:27844949:C:CA	donor_loss	1.0000
16:27844949:C:CC	donor_gain	1.0000
16:27845057:GAGGC:G	acceptor_gain	1.0000
16:27845059:GGC:G	acceptor_gain	1.0000
16:27845062:C:CC	acceptor_gain	1.0000
16:27845062:CTGTG:C	acceptor_loss	1.0000
16:27845063:T:A	acceptor_loss	1.0000
16:27884480:CCTTA:C	donor_loss	1.0000
16:27884481:CTTAC:C	donor_loss	1.0000
16:27884482:TTACC:T	donor_loss	1.0000
16:27884483:TA:T	donor_loss	1.0000
16:27884484:A:AC	donor_gain	1.0000
16:27884484:A:AT	donor_loss	1.0000
16:27884485:C:CC	donor_gain	1.0000
16:27884636:CCC:C	acceptor_gain	1.0000
16:27884637:CCC:C	acceptor_gain	1.0000
16:27884638:CCTGT:C	acceptor_loss	1.0000
16:27884639:C:CC	acceptor_gain	1.0000
16:27884639:C:G	acceptor_loss	1.0000
16:27888055:TTTAC:T	donor_loss	1.0000
16:27888056:TTACC:T	donor_loss	1.0000

AlphaMissense

2158 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:27828906:A:G	L238P	1.000
16:27828906:A:T	L238H	1.000
16:27828915:A:T	V235D	1.000
16:27828926:C:A	M231I	1.000
16:27828926:C:G	M231I	1.000
16:27828926:C:T	M231I	1.000
16:27828927:A:C	M231R	1.000
16:27828927:A:T	M231K	1.000
16:27828938:A:C	F227L	1.000
16:27828938:A:T	F227L	1.000
16:27828939:A:C	F227C	1.000
16:27828939:A:G	F227S	1.000
16:27828940:A:G	F227L	1.000
16:27828940:A:T	F227I	1.000
16:27828947:C:A	W224C	1.000
16:27828947:C:G	W224C	1.000
16:27828949:A:G	W224R	1.000
16:27828949:A:T	W224R	1.000
16:27844952:G:C	F220L	1.000
16:27844952:G:T	F220L	1.000
16:27844954:A:G	F220L	1.000
16:27844970:C:A	W214C	1.000
16:27844970:C:G	W214C	1.000
16:27844972:A:G	W214R	1.000
16:27844972:A:T	W214R	1.000
16:27844980:G:T	P211H	1.000
16:27844985:C:A	W209C	1.000
16:27844985:C:G	W209C	1.000
16:27844987:A:G	W209R	1.000
16:27844987:A:T	W209R	1.000

dbSNP variants (sampled 300 via entrez): RS1000021486 (16:28009599 C>T), RS1000024395 (16:28012197 C>A,T), RS1000080708 (16:28004656 T>C), RS1000081209 (16:27836907 A>G), RS1000090547 (16:27807106 A>G), RS1000098685 (16:28006271 C>T), RS1000105655 (16:28047255 A>G), RS1000108052 (16:27922278 C>T), RS1000137240 (16:27856900 T>C), RS1000142523 (16:27947241 C>T), RS1000144555 (16:27807341 C>A), RS1000146125 (16:27842543 T>A), RS1000151867 (16:27972791 T>G), RS1000167106 (16:27906049 C>T), RS1000172076 (16:28028991 C>T)

Disease associations

OMIM: gene MIM:617161 | disease phenotypes: MIM:256730

GenCC curated gene-disease

Mondo (1): neuronal ceroid lipofuscinosis (MONDO:0016295)

Orphanet (2): Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001762_64	Obesity-related traits	7.000000e-06
GCST009218_31	Lateral ventricle temporal horn volume	4.000000e-08
GCST010002_111	Refractive error	3.000000e-09
GCST012440_2	Hemoglobin levels in non-alcoholic fatty liver disease x mastiha supplementation interaction	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0600067	mastiha supplement exposure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
GSK-J4	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Allergens	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	affects cotreatment, decreases expression, increases abundance	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1
Valproic Acid	increases methylation	1
Particulate Matter	increases abundance, affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00337636	PHASE1	COMPLETED	Study of HuCNS-SC Cells in Patients With Infantile or Late Infantile Neuronal Ceroid Lipofuscinosis (NCL)
NCT01238315	PHASE1	WITHDRAWN	Safety and Efficacy Study of HuCNS-SC in Subjects With Neuronal Ceroid Lipofuscinosis
NCT07582484	PHASE1/PHASE2	NOT_YET_RECRUITING	Gene Therapy Trial for CLN6 Batten Disease
NCT01873924	Not specified	RECRUITING	Clinical and Neuropsychological Investigations in Batten Disease
NCT01966757	Not specified	COMPLETED	Neuronal Ceroid Lipofuscinosis and Associated Sleep Abnormalities
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
NCT06844877	Not specified	RECRUITING	Italian NCL Registry: a Registry for NCL as an Integration Tool for Future Therapeutic Strategies