GPR156

Summary

GPR156 (G protein-coupled receptor 156, HGNC:20844) is a protein-coding gene on chromosome 3q13.33, encoding Probable G-protein coupled receptor 156 (Q8NFN8). Orphan G-protein coupled receptor involved in the regulation of hair cell orientation in mechanosensory organs of the inner ear.

G protein-coupled receptors (GPCRs) are a large superfamily of cell surface receptors characterized by 7 helical transmembrane domains, together with N-terminal extracellular and C-terminal intracellular domains.

Source: NCBI Gene 165829 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal recessive 121 (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 138 total — 3 likely-pathogenic
• Phenotypes (HPO): 6
• Druggable target: yes
• MANE Select transcript: NM_153002

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20844
Approved symbol	GPR156
Name	G protein-coupled receptor 156
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	PGR28, GABABL
Ensembl gene	ENSG00000175697
Ensembl biotype	protein_coding
OMIM	610464
Entrez	165829

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000461057, ENST00000464295, ENST00000481907, ENST00000495912, ENST00000932327, ENST00000932328

RefSeq mRNA: 2 — MANE Select: NM_153002 NM_001168271, NM_153002

CCDS: CCDS2997, CCDS54629

Canonical transcript exons

ENST00000464295 — 10 exons

Exon	Start	End
ENSE00001235306	120181125	120181361
ENSE00001235315	120185299	120185394
ENSE00001235326	120186658	120186783
ENSE00001235337	120192939	120193049
ENSE00001235346	120193295	120193424
ENSE00001775238	120243640	120243776
ENSE00001924602	120285029	120285222
ENSE00001935064	120165478	120168384
ENSE00003487769	120173312	120173470
ENSE00003496201	120244003	120244478

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 92.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1021 / max 15.4988, expressed in 27 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44050	0.0847	19
44051	0.0174	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	92.18	gold quality
pancreatic ductal cell	CL:0002079	87.21	silver quality
upper arm skin	UBERON:0004263	85.39	gold quality
ganglionic eminence	UBERON:0004023	83.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.43	gold quality
left ventricle myocardium	UBERON:0006566	82.36	gold quality
kidney epithelium	UBERON:0004819	81.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.96	gold quality
epithelial cell of pancreas	CL:0000083	78.67	gold quality
ileal mucosa	UBERON:0000331	78.61	silver quality
cerebellar vermis	UBERON:0004720	77.26	gold quality
sperm	CL:0000019	76.64	gold quality
nasal cavity epithelium	UBERON:0005384	76.26	gold quality
quadriceps femoris	UBERON:0001377	76.04	gold quality
lateral nuclear group of thalamus	UBERON:0002736	75.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.40	gold quality
vastus lateralis	UBERON:0001379	74.49	gold quality
endothelial cell	CL:0000115	74.22	gold quality
body of tongue	UBERON:0011876	74.16	gold quality
subthalamic nucleus	UBERON:0001906	74.02	gold quality
pharyngeal mucosa	UBERON:0000355	73.70	gold quality
dorsal plus ventral thalamus	UBERON:0001897	73.51	gold quality
vena cava	UBERON:0004087	73.34	gold quality
secondary oocyte	CL:0000655	73.33	silver quality
layer of synovial tissue	UBERON:0007616	73.29	gold quality
cardia of stomach	UBERON:0001162	73.12	gold quality
tongue	UBERON:0001723	73.09	gold quality
thymus	UBERON:0002370	72.98	gold quality
saphenous vein	UBERON:0007318	72.93	gold quality
nipple	UBERON:0002030	72.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

72 targeting GPR156, 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-6748-5P	100.00	65.81	1057
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844

Literature-anchored findings (GeneRIF, showing 1)

• Novel GPR156 variants confirm its role in moderate sensorineural hearing loss. (PMID:37814107)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr156	ENSDARG00000086215
mus_musculus	Gpr156	ENSMUSG00000046961
rattus_norvegicus	Gpr156	ENSRNOG00000002797
drosophila_melanogaster	GABA-B-R2	FBGN0027575
caenorhabditis_elegans		WBGENE00022675

Paralogs (2): GABBR2 (ENSG00000136928), GABBR1 (ENSG00000204681)

Protein

Protein identifiers

Probable G-protein coupled receptor 156 — Q8NFN8 (reviewed: Q8NFN8)

Alternative names: G-protein coupled receptor PGR28, GABAB-related G-protein coupled receptor

All UniProt accessions (2): Q8NFN8, F8WAW3

UniProt curated annotations — full annotation on UniProt →

Function. Orphan G-protein coupled receptor involved in the regulation of hair cell orientation in mechanosensory organs of the inner ear. It is required to trigger a 180 degree reversal in hair cell orientation, creating a virtual line of polarity reversal (LPR) across which stereociliary bundles are arranged in opposite orientations.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous expression both in the CNS and in peripheral tissues. Very high expression in fetal brain and testis relative to expression in other tissues.

Disease relevance. Deafness, autosomal recessive, 121 (DFNB121) [MIM:620551] A form of non-syndromic deafness characterized by congenital or prelingual onset of moderate sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NFN8-1	1	yes
Q8NFN8-2	2

RefSeq proteins (2): NP_001161743, NP_694547* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002455	GPCR3_GABA-B	Family
IPR017978	GPCR_3_C	Domain
IPR041946	GPR156_7TM	Domain

Pfam: PF00003

UniProt features (52 total): helix 12, topological domain 8, compositionally biased region 8, transmembrane region 7, turn 4, strand 4, region of interest 3, sequence variant 2, chain 1, coiled-coil region 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8YK0	ELECTRON MICROSCOPY	2.4
8IEP	ELECTRON MICROSCOPY	2.61
8IEI	ELECTRON MICROSCOPY	2.62
8IEQ	ELECTRON MICROSCOPY	2.73
8IEB	ELECTRON MICROSCOPY	3.03
8YJP	ELECTRON MICROSCOPY	3.09
8IED	ELECTRON MICROSCOPY	3.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFN8-F1	55.77	0.11

Antibody-complex structures (SAbDab): 1 — 8IED

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 6

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): GOBP_GAMMA_AMINOBUTYRIC_ACID_SIGNALING_PATHWAY, GOBP_CELL_CELL_SIGNALING, CCANNAGRKGGC_UNKNOWN, TGIF_01, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, HP1SITEFACTOR_Q6, YNGTTNNNATT_UNKNOWN, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_RECEPTOR_COMPLEX, GOCC_PLASMA_MEMBRANE_PROTEIN_COMPLEX, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_GABA_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED

GO Biological Process (4): gamma-aminobutyric acid signaling pathway (GO:0007214), stereocilium bundle organization (GO:0160194), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (2): G protein-coupled GABA receptor activity (GO:0004965), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (3): plasma membrane (GO:0005886), G protein-coupled receptor heterodimeric complex (GO:0038039), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GABA receptor activity	2
G protein-coupled receptor activity	2
cell-cell signaling	1
cellular component organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
G protein-coupled receptor dimeric complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR156	GPR158	Q5T848	667
GPR156	GPRC5A	Q8NFJ5	580
GPR156	GPRC5B	Q9NZH0	528
GPR156	LRRC58	Q96CX6	503
GPR156	GPRC5C	Q9NQ84	492
GPR156	GPSM2	P81274	487
GPR156	GPRC5D	Q9NZD1	476
GPR156	GPRC6A	Q5T6X5	447
GPR156	GRIN2A	Q12879	431
GPR156	GRIN2B	Q13224	422
GPR156	GPR18	Q14330	408
GPR156	ZC3H6	P61129	404
GPR156	GABBR1	Q9UBS5	375
GPR156	PRM3	Q9NNZ6	371
GPR156	LYPD6B	Q8NI32	368

IntAct

11 interactions, top by confidence:

A	B	Type	Score
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
GPR156	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
GPR156	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR156	psi-mi:“MI:0915”(physical association)	0.400
GPR156	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	GPR156	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (129): ZNF564 (Affinity Capture-MS), RPUSD2 (Affinity Capture-MS), VANGL2 (Affinity Capture-MS), VANGL1 (Affinity Capture-MS), ZBTB1 (Affinity Capture-MS), ZNF444 (Affinity Capture-MS), NFKBIL1 (Affinity Capture-MS), AGAP3 (Affinity Capture-MS), PLD1 (Affinity Capture-MS), FARP2 (Affinity Capture-MS), SHQ1 (Affinity Capture-MS), MCRS1 (Affinity Capture-MS), PHTF2 (Affinity Capture-MS), PPP2R3B (Affinity Capture-MS), OBSL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GV85, A2ALI5, A2APT9, B0BN44, B1ARY8, B6ZI38, O14836, O35188, O55145, O60279, O60667, P07141, P09603, P0C8S2, P28906, P40225, P40226, P42705, P78423, Q06154, Q08DV9, Q13261, Q1ERP8, Q28270, Q2TB54, Q3UY90, Q4V9H3, Q4W8E7, Q5F267, Q5R770, Q60819, Q64314, Q6PAL1, Q6PCP7, Q6UXB8, Q80XI1, Q8BLK9, Q8CAE9, Q8CBC4, Q8JZQ0

Diamond homologs: G5ECB2, O75899, O88871, Q6PCP7, Q80T41, Q8K451, Q8NFN8, Q9UBS5, Q9WV18, Q9Z0U4, O70410, P23385, P31421, P31422, P31424, P41594, P91685, P97772, Q09630, Q13255, Q14416, Q14832, Q14BI2, Q1ZZH1, Q3UVX5, Q54SW3, Q55AP3, Q5RAL3, Q5U9X3, Q9QYS2, P35349, Q863I4, Q1ZXQ7, Q54L53, Q54LG8, Q54SH7, Q54SH8, Q55AP1, Q75JP4, Q75JT4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	112
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3064875	NM_153002.3(GPR156):c.1924del (p.Ser642fs)	Likely pathogenic
4292205	NM_153002.3(GPR156):c.696+1G>T	Likely pathogenic
4685463	NM_153002.3(GPR156):c.474+1del	Likely pathogenic

SpliceAI

1957 predictions. Top by Δscore:

Variant	Effect	Δscore
3:120168380:TTTTT:T	acceptor_gain	1.0000
3:120168381:TTTT:T	acceptor_gain	1.0000
3:120168382:TTT:T	acceptor_gain	1.0000
3:120168383:TT:T	acceptor_gain	1.0000
3:120168383:TTCT:T	acceptor_loss	1.0000
3:120168384:TCT:T	acceptor_loss	1.0000
3:120168385:C:CC	acceptor_gain	1.0000
3:120168385:C:CG	acceptor_loss	1.0000
3:120168386:T:A	acceptor_loss	1.0000
3:120173310:A:AC	donor_gain	1.0000
3:120173311:C:CC	donor_gain	1.0000
3:120173311:CTT:C	donor_gain	1.0000
3:120173313:T:TA	donor_gain	1.0000
3:120173466:TTCAG:T	acceptor_gain	1.0000
3:120173467:TCAG:T	acceptor_gain	1.0000
3:120173468:CAG:C	acceptor_gain	1.0000
3:120173468:CAGC:C	acceptor_gain	1.0000
3:120173469:AG:A	acceptor_gain	1.0000
3:120173469:AGCT:A	acceptor_loss	1.0000
3:120173470:GC:G	acceptor_loss	1.0000
3:120173471:C:A	acceptor_loss	1.0000
3:120173471:C:CC	acceptor_gain	1.0000
3:120173472:T:C	acceptor_loss	1.0000
3:120173474:T:C	acceptor_gain	1.0000
3:120173474:T:TC	acceptor_gain	1.0000
3:120186669:CA:C	donor_gain	1.0000
3:120243997:A:AC	donor_gain	1.0000
3:120243998:C:CC	donor_gain	1.0000
3:120243998:CTTA:C	donor_gain	1.0000
3:120243999:TTA:T	donor_loss	1.0000

AlphaMissense

5308 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:120193373:A:C	S95R	0.996
3:120193373:A:T	S95R	0.996
3:120193375:T:G	S95R	0.996
3:120192987:G:C	S142R	0.995
3:120192987:G:T	S142R	0.995
3:120192989:T:G	S142R	0.995
3:120168362:A:G	L372P	0.993
3:120193355:G:C	S101R	0.993
3:120193355:G:T	S101R	0.993
3:120193357:T:G	S101R	0.993
3:120193406:A:C	S84R	0.992
3:120193406:A:T	S84R	0.992
3:120193408:T:G	S84R	0.992
3:120168342:C:G	A379P	0.990
3:120243699:G:C	S58R	0.989
3:120243699:G:T	S58R	0.989
3:120243701:T:G	S58R	0.989
3:120192966:A:C	F149L	0.988
3:120192966:A:T	F149L	0.988
3:120192968:A:G	F149L	0.988
3:120192990:C:A	K141N	0.987
3:120192990:C:G	K141N	0.987
3:120186773:T:G	D162A	0.986
3:120186764:A:G	L165S	0.985
3:120193378:C:G	G94R	0.985
3:120193413:A:G	M82T	0.984
3:120185325:A:G	W224R	0.983
3:120185325:A:T	W224R	0.983
3:120193377:C:T	G94D	0.983
3:120168378:C:G	A367P	0.981

dbSNP variants (sampled 300 via entrez): RS1000004877 (3:120228054 G>C), RS1000173064 (3:120280330 T>C), RS1000238094 (3:120251259 G>A), RS1000240026 (3:120169856 C>T), RS1000297867 (3:120243898 A>C,G), RS1000306744 (3:120197285 G>A), RS1000356211 (3:120184264 A>T), RS1000386118 (3:120283706 G>C), RS1000420885 (3:120190127 A>G), RS1000423670 (3:120261313 TAA>T), RS1000443053 (3:120170080 T>C), RS1000521613 (3:120227688 A>G), RS1000538731 (3:120247417 T>C), RS1000539103 (3:120230678 C>T), RS1000542313 (3:120205794 ATTAT>A)

Disease associations

OMIM: gene MIM:610464 | disease phenotypes: MIM:220290, MIM:607197, MIM:620551

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal recessive 121	Strong	Autosomal recessive

Mondo (2): hearing loss, autosomal recessive (MONDO:0019588), hearing loss, autosomal recessive 121 (MONDO:0957825)

Orphanet (2): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000545	Myopia
HP:0001756	Vestibular hyporeflexia
HP:0003577	Congenital onset
HP:0011463	Childhood onset

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST006993_4	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-07
GCST010107_12	L-selectin levels	8.000000e-06
GCST011742_1	Triglyceride levels in HIV infection	9.000000e-06
GCST011742_13	Triglyceride levels in HIV infection	9.000000e-06
GCST012071_14	Response to selenium supplementation (change in plasma selenium concentration)	1.000000e-05
GCST90011900_23	Serum alkaline phosphatase levels	1.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0008202	L-Selectin measurement
EFO:0004530	triglyceride measurement
EFO:0600021	response to dietary selenium supplementation
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564609	Deafness, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523897 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Class C Orphans

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
bisphenol A	increases methylation	1
sodium arsenite	affects binding, increases reaction	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883423	Binding	PRESTO-Tango GPCRome screening (GPR156)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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