ADGRG1

adhesion G protein-coupled receptor G1, the group of Adhesion G protein-coupled receptors, subfamily G

Basic information

Region (hg38): 16:57610652-57665580

Previous symbols: [ "GPR56" ]

Links

ENSG00000205336 ∙ NCBI:9289 ∙ OMIM:604110 ∙ HGNC:4512 ∙ Uniprot:Q9Y653 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• bilateral frontoparietal polymicrogyria (Definitive), mode of inheritance: AR
• bilateral frontoparietal polymicrogyria (Definitive), mode of inheritance: AR
• bilateral frontoparietal polymicrogyria (Strong), mode of inheritance: AR
• bilateral frontoparietal polymicrogyria (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cortical dysplasia, complex, with other brain malformations-14A; Cortical dysplasia, complex, with other brain malformations 14B	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	15044805; 20929962; 21349848; 21723461; 23274687; 24531968
Variants involving cis-regulatory elements have additionally been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADGRG1 gene.

• not provided (61 variants)
• Bilateral frontoparietal polymicrogyria (14 variants)
• Bilateral frontoparietal polymicrogyria;Polymicrogyria, bilateral perisylvian, autosomal recessive (1 variants)
• Polymicrogyria, bilateral perisylvian, autosomal recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADGRG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	295	4	302
missense	2	9	132	13	3	159
nonsense	27	4	1			32
start loss						0
frameshift	32	3	2			37
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	8				11
splice region		1	8	50	2	61
non coding	1		32	157	72	262
Total	65	24	171	465	79

Highest pathogenic variant AF is 0.0000394

Variants in ADGRG1

This is a list of pathogenic ClinVar variants found in the ADGRG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-57620063-C-A		Bilateral frontoparietal polymicrogyria	Likely benign (Jan 13, 2018)
16-57620077-G-A		Bilateral frontoparietal polymicrogyria	Uncertain significance (Jan 12, 2018)
16-57620093-G-A		Bilateral frontoparietal polymicrogyria	Uncertain significance (Jan 13, 2018)
16-57620135-A-G		not specified	Likely benign (Aug 25, 2017)
16-57620144-A-T			Likely benign (May 10, 2018)
16-57620145-C-T		Bilateral frontoparietal polymicrogyria	Uncertain significance (Jan 13, 2018)
16-57628720-C-G			Likely benign (Feb 24, 2021)
16-57628855-A-T			Benign (Feb 24, 2021)
16-57628879-T-A			Benign (Feb 24, 2021)
16-57628885-AGAGTGT-A			Benign (Feb 24, 2021)
16-57628904-G-A			Benign (Feb 24, 2021)
16-57628915-A-T			Benign (Feb 24, 2021)
16-57628919-TGA-T			Benign (Feb 24, 2021)
16-57628925-T-A			Likely benign (Sep 17, 2019)
16-57628937-TGAGC-T			Benign (Feb 24, 2021)
16-57628943-TGA-T			Benign (Feb 24, 2021)
16-57628949-T-C			Benign (Feb 24, 2021)
16-57628953-A-T			Likely benign (Feb 24, 2021)
16-57628963-AGTGTGAGTGTGTGAGAGTGAGTGAGAATGTGAGTGT-A			Benign (Feb 24, 2021)
16-57628977-AGAGT-A			Benign (Jan 28, 2020)
16-57629021-C-A			Benign (Sep 17, 2019)
16-57639210-C-T			Benign (Jun 19, 2018)
16-57639373-CCAACGGTTGCCAGGG-C		Polymicrogyria, bilateral perisylvian, autosomal recessive	Pathogenic/Likely pathogenic (Feb 14, 2024)
16-57639378-G-A			Likely benign (Jan 31, 2024)
16-57639389-C-T			Likely benign (Jun 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADGRG1	protein_coding	protein_coding	ENST00000388812	13	54381

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.35e-10	0.954	125681	0	67	125748	0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0686	390	386	1.01	0.0000242	4508
Missense in Polyphen		106	122.54	0.865		1585
Synonymous	-1.15	195	176	1.11	0.0000118	1450
Loss of Function	2.07	20	32.8	0.610	0.00000189	330

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000476	0.000474
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000273	0.000272
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.000273	0.000272
South Asian	0.000686	0.000686
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor involved in cell adhesion and probably in cell- cell interactions. Mediates cell matrix adhesion in developing neurons and hematopoietic stem cells. Receptor for collagen III/COL3A1 in the developing brain and involved in regulation of cortical development, specifically in maintenance of the pial basement membrane integrity and in cortical lamination (By similarity). Binding to the COL3A1 ligand inhibits neuronal migration and activates the RhoA pathway by coupling to GNA13 and possibly GNA12 (PubMed:22238662). Plays a role in the maintenance of hematopoietic stem cells and/or leukemia stem cells in bone marrow niche (By similarity). Plays a critical role in cancer progression by inhibiting VEGFA production threreby inhibiting angiogenesis through a signaling pathway mediated by PRKCA (PubMed:16757564, PubMed:21724588). Plays an essential role in testis development (By similarity). {ECO:0000250|UniProtKB:Q8K209, ECO:0000269|PubMed:16757564, ECO:0000269|PubMed:19572147, ECO:0000269|PubMed:21708946, ECO:0000269|PubMed:21724588, ECO:0000269|PubMed:22238662, ECO:0000269|PubMed:24531968}.
• Disease: DISEASE: Polymicrogyria, bilateral frontoparietal (BFPP) [MIM:606854]: A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination, most severe in the frontoparietal regions. BFPP clinical manifestations include developmental and psychomotor delay, cerebellar and pyramidal signs, truncal ataxia, seizures, hyperreflexia. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. {ECO:0000269|PubMed:15044805, ECO:0000269|PubMed:16240336, ECO:0000269|PubMed:21349848, ECO:0000269|PubMed:21723461, ECO:0000269|PubMed:22238662, ECO:0000269|PubMed:24949629}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Polymicrogyria, bilateral perisylvian, autosomal recessive (BPPR) [MIM:615752]: A form of polymicrogyria, a malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination. BPPR is characterized by strikingly restricted polymicrogyria limited to the cortex surrounding the Sylvian fissure. Affected individuals have intellectual and language difficulty and seizures, but no motor disability. Polymicrogyria is a heterogeneous disorder, considered to be the result of post-migratory abnormal cortical organization. {ECO:0000269|PubMed:24531968}. Note=The disease is caused by mutations affecting the gene represented in this entry. Homozygous deletion of 1 of 2 tandem 15-bp repeats located 144 bp upstream of the ADGRG1 non-coding exon 1m transcription start site, results in impaired perisylvian ADGRG1 expression and disruption of perisylvian gyri (PubMed:24531968). {ECO:0000269|PubMed:24531968}.
• Pathway: GPCRs, Other (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.77

Haploinsufficiency Scores

• pHI: 0.155
• hipred: N
• hipred_score: 0.328
• ghis: 0.515

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Adgrg1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: adgrg1
• Affected structure: spinal cord
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: angiogenesis;cell adhesion;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;Rho protein signal transduction;cell-cell signaling;negative regulation of cell population proliferation;vascular endothelial growth factor production;cell migration;cerebral cortex regionalization;cerebral cortex radial glia guided migration;layer formation in cerebral cortex;positive regulation of Rho protein signal transduction;positive regulation of cell adhesion;protein kinase C signaling;seminiferous tubule development;positive regulation of neural precursor cell proliferation;negative regulation of neuron migration
• Cellular component: integral component of plasma membrane;integral component of membrane;membrane raft;extracellular exosome;glial limiting end-foot
• Molecular function: G protein-coupled receptor activity;collagen binding;heparin binding;extracellular matrix binding