GPR161

G protein-coupled receptor 161, the group of G protein-coupled receptors, Class A orphans

Basic information

Region (hg38): 1:168079541-168137667

Links

ENSG00000143147 ∙ NCBI:23432 ∙ OMIM:612250 ∙ HGNC:23694 ∙ Uniprot:Q8N6U8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pituitary stalk interruption syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Medulloblastoma predisposition syndrome	Ad	Oncologic	The condition can involve increased risk of medulloblastoma (and possibly other cancer types), and awareness may allow early disease detection and management	Oncologic	31609649

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPR161 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPR161 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				5	11	16
missense			38	1		39
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1	2	3
Total	0	0	39	7	13

Variants in GPR161

This is a list of pathogenic ClinVar variants found in the GPR161 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-168085562-T-C		Predisposition to medulloblastoma	Uncertain significance (Aug 04, 2022)
1-168085574-T-G		not specified	Uncertain significance (Jan 24, 2024)
1-168085603-T-A			Uncertain significance (Jan 04, 2024)
1-168085618-GC-G		Medulloblastoma	Uncertain significance (May 02, 2022)
1-168085630-G-A			Likely benign (Apr 16, 2018)
1-168085631-C-T		GPR161-related disorder	Likely benign (Sep 27, 2023)
1-168085647-G-A		not specified	Uncertain significance (May 24, 2024)
1-168085652-G-A		not specified	Uncertain significance (May 09, 2023)
1-168085655-A-C		not specified	Uncertain significance (Jan 30, 2024)
1-168085676-T-G		Medulloblastoma	Uncertain significance (Jun 29, 2022)
1-168085701-C-T		not specified	Uncertain significance (Jan 30, 2024)
1-168085708-C-T			Benign (Dec 12, 2023)
1-168085711-A-G			Likely benign (Apr 07, 2018)
1-168085712-A-G		not specified	Uncertain significance (Oct 26, 2021)
1-168085725-A-G			Benign (Apr 16, 2018)
1-168085781-G-A		not specified	Uncertain significance (Dec 21, 2023)
1-168087644-G-A		not specified	Uncertain significance (Oct 26, 2022)
1-168087674-G-A		Medulloblastoma	Uncertain significance (Aug 30, 2023)
1-168087678-A-G		Medulloblastoma • not specified	Uncertain significance (Jul 17, 2023)
1-168087697-A-T		not specified	Uncertain significance (Aug 04, 2022)
1-168090572-T-C		Medulloblastoma	Uncertain significance (May 23, 2022)
1-168090624-G-C		not specified	Uncertain significance (Jan 17, 2024)
1-168090628-A-G			Benign (Feb 01, 2024)
1-168090662-C-T			Uncertain significance (Dec 31, 2023)
1-168096494-A-T			Likely benign (Jan 10, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPR161	protein_coding	protein_coding	ENST00000537209	6	52825

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000349	0.990	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	254	332	0.766	0.0000196	3568
Missense in Polyphen		71	109.12	0.65066		1177
Synonymous	-1.54	161	138	1.17	0.00000858	1146
Loss of Function	2.28	9	20.0	0.450	0.00000104	212

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000376	0.000376
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000292	0.000290
Middle Eastern	0.00	0.00
South Asian	0.000264	0.000261
Other	0.000332	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key negative regulator of Shh signaling, which promotes the processing of GLI3 into GLI3R during neural tube development. Recruited by TULP3 and the IFT-A complex to primary cilia and acts as a regulator of the PKA-dependent basal repression machinery in Shh signaling by increasing cAMP levels, leading to promote the PKA-dependent processing of GLI3 into GLI3R and repress the Shh signaling. In presence of SHH, it is removed from primary cilia and is internalized into recycling endosomes, preventing its activity and allowing activation of the Shh signaling. Its ligand is unknown (By similarity). {ECO:0000250}.
• Pathway: Hedgehog signaling pathway - Homo sapiens (human);Hedgehog Signaling Pathway;GPCRs, Class A Rhodopsin-like;Signal Transduction;Hedgehog ,off, state;Signaling by Hedgehog (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.584
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.33

Haploinsufficiency Scores

• pHI: 0.156
• hipred: Y
• hipred_score: 0.554
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0652

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gpr161
• 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); growth/size/body region phenotype; craniofacial 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); limbs/digits/tail phenotype; pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: gpr161
• Affected structure: anterior lateral plate mesoderm
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: adenylate cyclase-activating G protein-coupled receptor signaling pathway;multicellular organism development;negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning
• Cellular component: cilium;integral component of membrane;endocytic vesicle membrane;recycling endosome;ciliary membrane
• Molecular function: G protein-coupled receptor activity