GPHA2

protein-coding

glycoprotein hormone subunit alpha 2, the group of Glycoprotein hormone subunits

Gene summary

GPHA2 is a cystine knot-forming polypeptide and a subunit of the dimeric glycoprotein hormone family (Hsu et al., 2002 [PubMed 12089349]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_130769.4

Inheritance

—

ClinVar variants

U:19B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.54

Max pathogenic AF

—

Genomic locus

chr11:64,934,471-64,935,893

External References & Databases

Ensembl (ENSG00000149735)

Transcript & Mutation Effects

hg38 • Region Span ~1.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPHA2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_130769.4. 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						0
missense			19 clinvar	2 clinvar		21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	19	2	0	21

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_130769.4	RefSeq	NP_570125.1	3	MANE Select
ENST00000279168.7	Ensembl	ENSP00000279168.2	3	MANE Select
ENST00000532246.1	Ensembl	ENSP00000431352.1	2	Standard
ENST00000532246.2	Ensembl	ENSP00000431352.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
G alpha (s) signalling events
Hormone ligand-binding receptors
Class A/1 (Rhodopsin-like receptors)

Biological Process

cell surface receptor signaling pathway
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway
regulation of signaling receptor activity

Molecular Function

hormone activity
protein binding
thyrotropin-releasing hormone receptor binding
protein heterodimerization activity
hormone receptor binding

Cellular Component

extracellular region
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000279168
Coding exons: 3
Length: 1418
Individuals with no LoFs: 125592
Homozygous LoFs: 1
Heterozygous LoFs: 155
Defined: 125748
p: 0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0897	75	77.2	0.971	0.00000491	821
Missense (PolyPhen)		38	33.643	1.1295		365
Synonymous	0.605	27	31.3	0.862	0.00000185	272
Loss of Function	-1.27	10	6.51	1.54	4.49e-7	56

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.00062	0.00058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00071	0.00071	rare
Finnish	0.0030	0.0029	notable
European (Non-Finnish)	0.00042	0.00041	rare
South Asian	0.000039	0.000033	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a heterodimeric glycoprotein hormone with GPHB5 able to bind and activate the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production (PubMed:12045258). Plays a central role in controlling thyroid cell metabolism (PubMed:12045258). {ECO:0000269|PubMed:12045258}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.648
RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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