GPHRB

Summary

GPHRB (golgi pH regulator B, HGNC:13840) is a protein-coding gene on chromosome 1q21.2, encoding Golgi pH regulator B (P0CG08). Voltage-gated channel that enables the transfer of anions such as iodide, chloride, bromide and fluoride which may function in counter-ion conductance and participates in Golgi acidification.

Enables voltage-gated monoatomic anion channel activity. Involved in intracellular pH reduction. Located in Golgi cisterna membrane and Golgi-associated vesicle membrane.

Source: NCBI Gene 51463 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 22 total — 5 pathogenic
• MANE Select transcript: NM_016334

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13840
Approved symbol	GPHRB
Name	golgi pH regulator B
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	GPHRB, SH120
Ensembl gene	ENSG00000188092
Ensembl biotype	protein_coding
OMIM	612806
Entrez	51463

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron

ENST00000314163, ENST00000461786, ENST00000468618, ENST00000478307, ENST00000488165, ENST00000488603, ENST00000490955, ENST00000491975, ENST00000902713, ENST00000902714, ENST00000935961, ENST00000935962, ENST00000970056, ENST00000970057

RefSeq mRNA: 6 — MANE Select: NM_016334 NM_001350180, NM_001350181, NM_001350182, NM_001350183, NM_001350184, NM_016334

CCDS: CCDS930

Canonical transcript exons

ENST00000314163 — 14 exons

Exon	Start	End
ENSE00003544211	147936627	147936686
ENSE00003556238	147992502	147992567
ENSE00003603001	147968875	147968963
ENSE00003646302	147986199	147986294
ENSE00003648755	147988432	147988521
ENSE00003662903	147969867	147969959
ENSE00003667605	147966554	147966663
ENSE00003691031	147992711	147993592
ENSE00003696110	147943997	147944098
ENSE00003697147	147953345	147953465
ENSE00003699851	147943438	147943544
ENSE00003700718	147954322	147954402
ENSE00003701321	147938714	147938817
ENSE00003894435	147928420	147928578

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 90.11.

FANTOM5 (CAGE): breadth not_expressed, TPM avg 0.0014 / max 0.9340, expressed in 0 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4990	0.0010	0
4991	0.0004	0

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.11	gold quality
duodenum	UBERON:0002114	88.67	gold quality
corpus callosum	UBERON:0002336	88.19	gold quality
calcaneal tendon	UBERON:0003701	87.96	gold quality
adult mammalian kidney	UBERON:0000082	87.03	gold quality
body of pancreas	UBERON:0001150	87.00	gold quality
granulocyte	CL:0000094	86.01	gold quality
kidney	UBERON:0002113	85.74	gold quality
cerebellar cortex	UBERON:0002129	85.71	gold quality
cerebellar hemisphere	UBERON:0002245	85.70	gold quality
cerebellum	UBERON:0002037	85.61	gold quality
right lobe of liver	UBERON:0001114	85.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.19	gold quality
liver	UBERON:0002107	84.86	gold quality
pancreas	UBERON:0001264	84.70	gold quality
cortex of kidney	UBERON:0001225	84.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.27	gold quality
body of stomach	UBERON:0001161	84.04	gold quality
small intestine	UBERON:0002108	83.84	gold quality
endometrium	UBERON:0001295	83.44	gold quality
bone marrow cell	CL:0002092	83.30	gold quality
metanephros cortex	UBERON:0010533	83.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.10	gold quality
skin of leg	UBERON:0001511	82.88	gold quality
zone of skin	UBERON:0000014	82.84	gold quality
testis	UBERON:0000473	82.78	gold quality
stomach	UBERON:0000945	82.78	gold quality
lymph node	UBERON:0000029	82.72	gold quality
skin of abdomen	UBERON:0001416	82.63	gold quality
tonsil	UBERON:0002372	82.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting GPHRB, 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-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-6728-3P	98.63	67.63	1534

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	GPR89A	ENSDARG00000077983
mus_musculus	Gpr89	ENSMUSG00000028096
rattus_norvegicus	Gpr89b	ENSRNOG00000000095
drosophila_melanogaster	GPHR	FBGN0033995
caenorhabditis_elegans		WBGENE00007528
caenorhabditis_elegans		WBGENE00013551

Paralogs (1): GPR89A (ENSG00000117262)

Protein

Protein identifiers

Golgi pH regulator B — P0CG08 (reviewed: P0CG08)

Alternative names: Protein GPR89B

All UniProt accessions (6): P0CG08, A0A087WW78, A0A087WW82, U3KPV2, X5D7G6, X5DNN3

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-gated channel that enables the transfer of anions such as iodide, chloride, bromide and fluoride which may function in counter-ion conductance and participates in Golgi acidification. Plays a role in lymphocyte development, probably by acting as a RABL3 effector in hematopoietic cells.

Subunit / interactions. Homotrimer. Interacts with RABL3; the interaction stabilizes GPR89B.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Ubiquitous.

Miscellaneous. Does not seem to be able to bind GTP.

Similarity. Belongs to the Golgi pH regulator (TC 1.A.38) family.

RefSeq proteins (6): NP_001337109, NP_001337110, NP_001337111, NP_001337112, NP_001337113, NP_057418* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015672	GPHR/GTG	Family
IPR022535	Golgi_pH-regulator_cons_dom	Domain
IPR025969	ABA_GPCR_dom	Domain

Pfam: PF12430, PF12537

Catalyzed reactions (Rhea), 4 shown:

• chloride(in) = chloride(out) (RHEA:29823)
• iodide(out) = iodide(in) (RHEA:66324)
• bromide(in) = bromide(out) (RHEA:75383)
• fluoride(in) = fluoride(out) (RHEA:76159)

UniProt features (15 total): transmembrane region 9, sequence conflict 3, glycosylation site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CG08-F1	82.78	0.36

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 (2): 180, 243

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): ONKEN_UVEAL_MELANOMA_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_REGULATION_OF_PH, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_GOLGI_STACK, chr1q21, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, GRYDER_PAX3FOXO1_TOP_ENHANCERS, GOCC_GOLGI_CISTERNA, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, GOBP_HOMEOSTATIC_PROCESS, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (6): protein transport (GO:0015031), T cell differentiation (GO:0030217), intracellular pH reduction (GO:0051452), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (2): voltage-gated monoatomic anion channel activity (GO:0008308), protein binding (GO:0005515)

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi cisterna membrane (GO:0032580), monoatomic ion channel complex (GO:0034702), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
intracellular protein localization	1
establishment of protein localization	1
lymphocyte differentiation	1
T cell activation	1
regulation of intracellular pH	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic anion transport	1
monoatomic ion transmembrane transport	1
voltage-gated monoatomic ion channel activity	1
monoatomic anion channel activity	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
Golgi cisterna	1
transmembrane transporter complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

62 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
GPR89B	WFS1	psi-mi:“MI:0915”(physical association)	0.560
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
B4GALT3	SLC19A2	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3B1	psi-mi:“MI:0914”(association)	0.530
P2RY1	SLC19A2	psi-mi:“MI:0914”(association)	0.530
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	TPST1	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC7A1	STXBP3	psi-mi:“MI:0914”(association)	0.530
GPR89B	NOLC1	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ST3GAL1	ITGAV	psi-mi:“MI:0914”(association)	0.350
SLC4A8	ABCC4	psi-mi:“MI:0914”(association)	0.350
TXNDC15	ORC4	psi-mi:“MI:0914”(association)	0.350
SERINC1	GPR89B	psi-mi:“MI:0914”(association)	0.350
	SLC19A2	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
GABBR1	PPP1R12A	psi-mi:“MI:0914”(association)	0.350

BioGRID (246): GPR89A (Affinity Capture-MS), GPR89A (Affinity Capture-MS), GPR89B (Affinity Capture-MS), GPR89B (Affinity Capture-MS), GPR89A (Affinity Capture-MS), GPR89A (Affinity Capture-MS), GPR89B (Affinity Capture-MS), GPR89A (Affinity Capture-MS), GPR89B (Affinity Capture-MS), GPR89A (Affinity Capture-MS), GPR89B (Affinity Capture-MS), GPR89B (Affinity Capture-MS), GPR89A (Affinity Capture-MS), GPR89B (Affinity Capture-MS), GPR89B (Affinity Capture-MS)

ESM2 similar proteins: B2ZXD5, B5X1G3, B7ZAQ6, B9RK42, O95214, P0CG08, Q0VGV9, Q32PD8, Q3B8G4, Q3SYY9, Q3ZBX1, Q4R5E3, Q5BIM9, Q5E9M1, Q5F3F5, Q5F433, Q5F448, Q5PQQ4, Q5PR61, Q5RDE9, Q5U4X7, Q5ZI05, Q658I5, Q68DH5, Q6AZ61, Q6CLZ9, Q6DDW6, Q6DFS0, Q6IQC7, Q6P4P2, Q6PDU4, Q7SYR6, Q7ZUA6, Q7ZX75, Q7ZYA0, Q8BH79, Q8BS95, Q8C561, Q8GWT5, Q8K0B2

Diamond homologs: A2XX57, B2ZXD5, B5X1G3, B7ZAQ6, P0CG08, Q0WQG8, Q54QM5, Q5BIM9, Q5F448, Q6DDW6, Q7X7S8, Q8BS95, Q9XIP7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
chloride transmembrane transport	6	17.8×	2e-04
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	16.4×	3e-04
transport across blood-brain barrier	6	13.4×	8e-04
positive regulation of cytosolic calcium ion concentration	9	13.2×	1e-05
adenylate cyclase-activating G protein-coupled receptor signaling pathway	7	9.9×	8e-04
G protein-coupled receptor signaling pathway	14	6.3×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
149503	GRCh38/hg38 1q21.1-21.2(chr1:146987841-148352084)x1	Pathogenic
1879126	GRCh37/hg19 1q21.1-21.2(chr1:145365287-147416212)x1	Pathogenic
565158	GRCh37/hg19 1q21.1-21.2(chr1:145733443-147929323)x1	Pathogenic
565168	GRCh37/hg19 1q21.1-21.2(chr1:145792051-148846369)x1	Pathogenic
666434	GRCh37/hg19 1q21.1-21.2(chr1:145804679-147735815)x3	Pathogenic

SpliceAI

2896 predictions. Top by Δscore:

Variant	Effect	Δscore
1:147936621:CTCCA:C	acceptor_loss	1.0000
1:147936622:TCCA:T	acceptor_loss	1.0000
1:147936623:CCA:C	acceptor_loss	1.0000
1:147936624:CAGAT:C	acceptor_loss	1.0000
1:147936625:AGA:A	acceptor_loss	1.0000
1:147936626:G:A	acceptor_loss	1.0000
1:147966655:G:GT	donor_gain	1.0000
1:147966661:A:T	donor_gain	1.0000
1:147986193:TTGCA:T	acceptor_loss	1.0000
1:147986194:TGCA:T	acceptor_loss	1.0000
1:147986194:TGCAG:T	acceptor_loss	1.0000
1:147986195:GCA:G	acceptor_loss	1.0000
1:147986195:GCAGG:G	acceptor_loss	1.0000
1:147986196:CAGGC:C	acceptor_loss	1.0000
1:147986197:A:AC	acceptor_loss	1.0000
1:147986197:A:AG	acceptor_gain	1.0000
1:147986198:G:GC	acceptor_loss	1.0000
1:147986198:G:GG	acceptor_gain	1.0000
1:147986291:TGATG:T	donor_loss	1.0000
1:147986292:GAT:G	donor_gain	1.0000
1:147986293:AT:A	donor_gain	1.0000
1:147986294:TG:T	donor_loss	1.0000
1:147986294:TGT:T	donor_loss	1.0000
1:147986295:G:GG	donor_gain	1.0000
1:147986295:GTA:G	donor_loss	1.0000
1:147986295:GTAA:G	donor_loss	1.0000
1:147986296:T:A	donor_loss	1.0000
1:147988422:AT:A	acceptor_gain	1.0000
1:147988422:ATGGT:A	acceptor_gain	1.0000
1:147988423:T:G	acceptor_gain	1.0000

AlphaMissense

3025 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:147943454:T:A	W75R	1.000
1:147943454:T:C	W75R	1.000
1:147953380:G:C	G151R	1.000
1:147953389:G:A	G154R	1.000
1:147953389:G:C	G154R	1.000
1:147953390:G:A	G154E	1.000
1:147953405:C:A	A159D	1.000
1:147953416:G:A	G163R	1.000
1:147953416:G:C	G163R	1.000
1:147953417:G:A	G163E	1.000
1:147953417:G:T	G163V	1.000
1:147953423:G:A	G165D	1.000
1:147953426:C:A	A166D	1.000
1:147953429:T:A	V167D	1.000
1:147969897:G:A	G283R	1.000
1:147969897:G:C	G283R	1.000
1:147969918:G:C	G290R	1.000
1:147986245:T:A	V319D	1.000
1:147988471:G:A	G349R	1.000
1:147988471:G:C	G349R	1.000
1:147988472:G:A	G349E	1.000
1:147992711:G:C	G388R	1.000
1:147992739:T:C	L397P	1.000
1:147992769:G:C	R407P	1.000
1:147992804:T:C	F419L	1.000
1:147992806:C:A	F419L	1.000
1:147992806:C:G	F419L	1.000
1:147992810:T:C	F421L	1.000
1:147992812:C:A	F421L	1.000
1:147992812:C:G	F421L	1.000

dbSNP variants (sampled 300 via entrez): RS111351195 (1:147931479 T>A), RS111406915 (1:147953519 T>C), RS111483535 (1:147945521 A>G), RS111630648 (1:147985979 A>G), RS112166383 (1:147938388 A>G), RS112499209 (1:147944215 T>G), RS112752806 (1:147980884 C>T), RS11304552 (1:147929790 G>GT), RS113629891 (1:147967250 C>T), RS113639633 (1:147982066 T>C), RS113697330 (1:147980659 A>G), RS113750974 (1:147933941 A>G), RS113872725 (1:147927522 ATC>A), RS11485698 (1:147942119 A>C), RS11488331 (1:147941826 A>G)

Disease associations

OMIM: gene MIM:612806 | disease phenotypes: MIM:612475

GenCC curated gene-disease

Mondo (1): chromosome 1q21.1 duplication syndrome (MONDO:0012915)

Orphanet (1): 1q21.1 microduplication syndrome (Orphanet:250994)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567290	Chromosome 1q21.1 Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
beta-lapachone	increases expression	1
sodium arsenite	increases abundance, increases expression	1
azoxystrobin	increases expression	1
pyrachlostrobin	increases expression	1
picoxystrobin	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic	increases abundance, increases expression	1
Calcium Chloride	increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight