GPHRA

Summary

GPHRA (golgi pH regulator A, HGNC:31984) is a protein-coding gene on chromosome 1q21.1, encoding Golgi pH regulator A (B7ZAQ6). Voltage-gated channel that enables the transfer of monoatomic 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 653519 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total — 1 likely-pathogenic
• MANE Select transcript: NM_001097612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31984
Approved symbol	GPHRA
Name	golgi pH regulator A
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	GPHR, UNQ192
Ensembl gene	ENSG00000117262
Ensembl biotype	protein_coding
OMIM	612821
Entrez	653519

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000313835, ENST00000460277, ENST00000462900, ENST00000465185, ENST00000466593, ENST00000478703, ENST00000492401, ENST00000493684, ENST00000524525, ENST00000527989, ENST00000528944, ENST00000532574, ENST00000534502, ENST00000907153, ENST00000907154, ENST00000907155, ENST00000907156, ENST00000907157, ENST00000907158, ENST00000907159, ENST00000907160, ENST00000918431, ENST00000960869

RefSeq mRNA: 2 — MANE Select: NM_001097612 NM_001097612, NM_001097613

CCDS: CCDS72857, CCDS72858

Canonical transcript exons

ENST00000313835 — 14 exons

Exon	Start	End
ENSE00001597907	145623613	145623714
ENSE00001863261	145669834	145670650
ENSE00003473687	145665562	145665651
ENSE00003476736	145646184	145646272
ENSE00003514696	145623054	145623160
ENSE00003518078	145663329	145663424
ENSE00003548922	145647175	145647267
ENSE00003553143	145669625	145669690
ENSE00003555340	145643869	145643978
ENSE00003559230	145616234	145616293
ENSE00003595763	145631664	145631744
ENSE00003625983	145630687	145630807
ENSE00003668603	145618320	145618423
ENSE00003846947	145607988	145608175

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 91.42.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9157 / max 13.2807, expressed in 607 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201670	0.9157	607

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	91.42	gold quality
duodenum	UBERON:0002114	91.32	gold quality
body of pancreas	UBERON:0001150	89.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.90	gold quality
pancreas	UBERON:0001264	88.88	gold quality
endometrium	UBERON:0001295	88.80	gold quality
cerebellar cortex	UBERON:0002129	88.57	gold quality
cerebellar hemisphere	UBERON:0002245	88.54	gold quality
cerebellum	UBERON:0002037	88.53	gold quality
adrenal tissue	UBERON:0018303	88.34	gold quality
rectum	UBERON:0001052	88.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.28	gold quality
calcaneal tendon	UBERON:0003701	88.19	gold quality
right lobe of liver	UBERON:0001114	88.00	gold quality
islet of Langerhans	UBERON:0000006	87.99	gold quality
body of stomach	UBERON:0001161	87.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.57	gold quality
left adrenal gland cortex	UBERON:0035825	87.55	gold quality
smooth muscle tissue	UBERON:0001135	87.46	gold quality
left adrenal gland	UBERON:0001234	87.43	gold quality
adult mammalian kidney	UBERON:0000082	87.32	gold quality
right adrenal gland	UBERON:0001233	87.26	gold quality
right adrenal gland cortex	UBERON:0035827	87.24	gold quality
adrenal gland	UBERON:0002369	87.16	gold quality
stomach	UBERON:0000945	87.05	gold quality
pituitary gland	UBERON:0000007	87.04	gold quality
cortex of kidney	UBERON:0001225	87.02	gold quality
kidney	UBERON:0002113	87.00	gold quality
adenohypophysis	UBERON:0002196	86.95	gold quality
small intestine	UBERON:0002108	86.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92
E-CURD-112	no	3.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting GPHRA, 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-8068	99.98	73.85	2376
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
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-6728-3P	98.63	67.63	1534
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-937-5P	97.43	68.39	667
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3622B-3P	96.82	66.36	988

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): GPR89B (ENSG00000188092)

Protein

Protein identifiers

Golgi pH regulator A — B7ZAQ6 (reviewed: B7ZAQ6)

Alternative names: Protein GPR89A, Putative MAPK-activating protein PM01, Putative NF-kappa-B-activating protein 90

All UniProt accessions (5): B7ZAQ6, E9PKY3, E9PRZ5, X5D7G6, X5DNN3

UniProt curated annotations — full annotation on UniProt →

Function. Voltage-gated channel that enables the transfer of monoatomic 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 GPR89A.

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.

Isoforms (4)

UniProt ID	Names	Canonical?
B7ZAQ6-1	1	yes
B7ZAQ6-2	2
B7ZAQ6-3	3
B7ZAQ6-4	4, A

RefSeq proteins (2): NP_001091081, NP_001091082 (=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 (19 total): transmembrane region 9, splice variant 4, sequence conflict 3, glycosylation site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B7ZAQ6-F1	82.62	0.35

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: 80 (showing top): GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_GOLGI_ASSOCIATED_VESICLE, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, SANSOM_APC_TARGETS_DN, GOBP_REGULATION_OF_PH, GOBP_MONOATOMIC_ION_HOMEOSTASIS, MORI_PLASMA_CELL_UP, GOBP_POSITIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_GOLGI_STACK, chr1q21, GOCC_GOLGI_ASSOCIATED_VESICLE_MEMBRANE, GOCC_GOLGI_CISTERNA, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (7): protein transport (GO:0015031), T cell differentiation (GO:0030217), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), 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 (1): voltage-gated monoatomic anion channel activity (GO:0008308)

GO Cellular Component (6): Golgi membrane (GO:0000139), Golgi-associated vesicle membrane (GO:0030660), 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
bounding membrane of organelle	2
intracellular protein localization	1
establishment of protein localization	1
lymphocyte differentiation	1
T cell activation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	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
Golgi apparatus	1
Golgi-associated vesicle	1
cytoplasmic vesicle membrane	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

908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPHRA	CT47A11	Q5JQC4	952
GPHRA	CT47B1	P0C2W7	766
GPHRA	ACP6	Q9NPH0	636
GPHRA	FSHR	P23945	602
GPHRA	TSHR	P16473	599
GPHRA	PRKAB2	O43741	595
GPHRA	FMO5	P49326	576
GPHRA	POLR3GL	Q9BT43	539
GPHRA	CHD1L	Q86WJ1	530
GPHRA	BOLA2	Q9H3K6	528
GPHRA	GPHN	Q9NQX3	515
GPHRA	LHCGR	P22888	512
GPHRA	GPR152	Q8TDT2	508
GPHRA	NBPF11	Q86T75	507
GPHRA	GTPBP8	Q8N3Z3	488

IntAct

111 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6		psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
M	DENND11	psi-mi:“MI:0914”(association)	0.350
ATP2B2	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350
BSCL2	TMEM223	psi-mi:“MI:0914”(association)	0.350
ADGRE5	TMEM223	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	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 113 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Amino acid transport across the plasma membrane	7	30.1×	2e-07
SLC-mediated transport of neurotransmitters	5	29.1×	2e-05
R-HSA-425366	8	20.7×	2e-07
R-HSA-425393	8	14.8×	2e-06
SLC-mediated transmembrane transport	14	11.8×	1e-09
G alpha (q) signalling events	10	8.2×	1e-05
Cardiac conduction	5	7.8×	5e-03
Transport of small molecules	18	6.5×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
complement receptor mediated signaling pathway	5	56.7×	2e-06
amino acid transport	10	31.5×	4e-10
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	5	17.0×	5e-04
sodium ion transmembrane transport	8	16.4×	3e-06
transport across blood-brain barrier	9	16.3×	7e-07
phospholipase C-activating G protein-coupled receptor signaling pathway	12	16.0×	4e-09
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	13.3×	4e-04
positive regulation of cytosolic calcium ion concentration	9	10.6×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	42
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1331349	NC_000001.10:g.145382933_145831892del	Likely pathogenic

SpliceAI

2637 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145616230:T:A	acceptor_loss	1.0000
1:145616231:C:CC	acceptor_gain	1.0000
1:145616231:C:CG	acceptor_loss	1.0000
1:145616232:TCTG:T	acceptor_loss	1.0000
1:145616233:ATCT:A	acceptor_loss	1.0000
1:145616235:GTAT:G	acceptor_gain	1.0000
1:145616292:CC:C	donor_loss	1.0000
1:145616293:A:AG	donor_loss	1.0000
1:145616294:CAC:C	donor_loss	1.0000
1:145616295:TCAC:T	donor_loss	1.0000
1:145616296:CTCAC:C	donor_loss	1.0000
1:145616297:TCTCA:T	donor_loss	1.0000
1:145643969:T:TA	donor_gain	1.0000
1:145643974:T:A	donor_gain	1.0000
1:145663325:T:A	acceptor_loss	1.0000
1:145663326:C:CC	acceptor_gain	1.0000
1:145663329:AGCC:A	acceptor_loss	1.0000
1:145663330:TAGCC:T	acceptor_loss	1.0000
1:145663423:C:CC	donor_gain	1.0000
1:145663423:CAT:C	donor_gain	1.0000
1:145663424:A:AC	donor_gain	1.0000
1:145663424:AC:A	donor_loss	1.0000
1:145663425:TACAT:T	donor_loss	1.0000
1:145663426:TTA:T	donor_loss	1.0000
1:145663427:CTTA:C	donor_loss	1.0000
1:145663428:ACTT:A	donor_loss	1.0000
1:145665551:A:T	acceptor_gain	1.0000
1:145665552:C:CT	acceptor_gain	1.0000
1:145665552:C:T	acceptor_gain	1.0000
1:145665555:C:CT	acceptor_gain	1.0000

AlphaMissense

3026 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS10910846 (1:145659481 G>A,C,T), RS111338698 (1:145659066 C>A,T), RS111383109 (1:145619259 A>C), RS111488177 (1:145641195 A>C), RS111533600 (1:145630557 A>T), RS111534447 (1:145634351 G>A), RS111649805 (1:145640511 A>G), RS111653456 (1:145652195 T>G), RS111698165 (1:145647104 G>A), RS111776936 (1:145659392 G>A), RS111781764 (1:145616956 G>C), RS111884698 (1:145620881 T>G), RS112052396 (1:145607628 G>C), RS112053125 (1:145666774 G>A,T), RS112067935 (1:145653884 T>A)

Disease associations

OMIM: gene MIM:612821 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
abrine	increases expression	1
pyrachlostrobin	increases expression	1
jinfukang	increases expression	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cannabidiol	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Rotenone	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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