GPR101

protein-coding

G protein-coupled receptor 101, the group of G protein-coupled receptors, Class A orphans

Gene summary

The protein encoded by this gene is an orphan G protein-coupled receptor of unknown function. The encoded protein is a member of a family of proteins that contain seven transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. [provided by RefSeq, Sep 2011]

MANE transcript

NM_054021.2

Inheritance

ClinVar variants

P:1U:59B:41

Top phenotype

Pituitary adenoma, growth hormone secreting, 2

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chrX:137,023,929-137,033,995

External References & Databases

Ensembl (ENSG00000165370)

Transcript & Mutation Effects

hg38 • Region Span ~10.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

acromegalySUPPORTIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0019933

Submitter: Orphanet

pituitary adenoma, growth hormone-secreting, 2STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010492

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Pituitary adenoma, growth hormone secreting, 2XL

Manifestation: Endocrine

Intervention: Endocrine

Rationale: Surveillance and/or awareness of cancer risk may allow early diagnosis of pituitary tumors (as well as related manifestations, such as hypertension, hypogonadism, diabetes mellitus, and osteoporosis), which could potentially be beneficial to allow early medical (eg, with somatostatin analogs, growth hormone receptor antagonists, dopamine agonists) or surgical treatment; Surveillance post-treatment may also be beneficial to detect recurrence/new adenomas

Comments: The condition can involve microduplications including the gene

Refs: 25470569; 25806920

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPR101 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 71

not providedTotal: 44

GPR101-related disorderTotal: 4

Pituitary adenoma, growth hormone-secreting, 2Total: 4

X-linked acrogigantism due to Xq26 microduplicationTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_054021.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				21 clinvar	3 clinvar	24
missense	1 clinvar		59 clinvar	13 clinvar	4 clinvar	77
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	59	34	7	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_054021.2	RefSeq	NP_473362.1	1	MANE Select
ENST00000651716.2	Ensembl	ENSP00000498972.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

adenylate cyclase-modulating G protein-coupled receptor signaling pathway
adenylate cyclase-activating adrenergic receptor signaling pathway

Molecular Function

adrenergic receptor activity

Cellular Component

integral component of plasma membrane
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298110
Coding exons: 1
Length: 1527
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.635	181	207	0.876	0.0000154	3372
Missense (PolyPhen)		63	74.963	0.84041		1261
Synonymous	0.985	75	86.7	0.865	0.00000680	1001
Loss of Function	2.35	1	8.30	0.120	5.65e-7	148

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor.;
Disease: DISEASE: Pituitary adenoma 2, growth hormone-secreting (PITA2) [MIM:300943]: A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete. PITA2 is a growth hormone-secreting benign neoplasm, also known as somatotropinoma. It clinically results in acromegaly, a condition characterized by coarse facial features, protruding jaw, and enlarged extremities. Excessive production of growth hormone in children or adolescents before the closure of epiphyses causes gigantism, a condition characterized by abnormally tall stature. {ECO:0000269|PubMed:25470569}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0993

Intolerance Scores

LoFtool: 0.117
RVIS EVS: 0.66
RVIS percentile EVS: 84.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.207

Gene Damage Prediction

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