GPR143

Summary

GPR143 (G protein-coupled receptor 143, HGNC:20145) is a protein-coding gene on chromosome Xp22.2, encoding G-protein coupled receptor 143 (P51810). Receptor for tyrosine, L-DOPA and dopamine.

This gene encodes a protein that binds to heterotrimeric G proteins and is targeted to melanosomes in pigment cells. This protein is thought to be involved in intracellular signal transduction mechanisms. Mutations in this gene cause ocular albinism type 1, also referred to as Nettleship-Falls type ocular albinism, a severe visual disorder. A related pseudogene has been identified on chromosome Y.

Source: NCBI Gene 4935 — RefSeq curated summary.

At a glance

• Gene–disease (curated): GPR143-related foveal hypoplasia (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 508 total — 94 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes
• MANE Select transcript: NM_000273

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20145
Approved symbol	GPR143
Name	G protein-coupled receptor 143
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101850
Ensembl biotype	protein_coding
OMIM	300808
Entrez	4935

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000431126, ENST00000447366, ENST00000467482, ENST00000480178, ENST00000487206, ENST00000911141, ENST00000929112, ENST00000929113, ENST00000929114

RefSeq mRNA: 1 — MANE Select: NM_000273 NM_000273

CCDS: CCDS14134

Canonical transcript exons

ENST00000467482 — 9 exons

Exon	Start	End
ENSE00000664799	9741338	9741455
ENSE00000664801	9746044	9746153
ENSE00001290259	9759332	9759426
ENSE00001819434	9765568	9765847
ENSE00001910604	9725346	9725840
ENSE00003504812	9748574	9748666
ENSE00003538536	9760717	9760826
ENSE00003593346	9739485	9739719
ENSE00003790350	9743565	9743673

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 94.07.

FANTOM5 (CAGE): breadth broad, TPM avg 9.1618 / max 457.2016, expressed in 609 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198373	6.5423	315
198372	0.5269	100
198378	0.4875	301
198377	0.4632	260
198376	0.4560	223
198374	0.3890	151
198375	0.1918	121
198370	0.1051	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.07	gold quality
secondary oocyte	CL:0000655	93.23	gold quality
pigmented layer of retina	UBERON:0001782	90.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.76	gold quality
caudate nucleus	UBERON:0001873	77.86	gold quality
metanephros cortex	UBERON:0010533	77.11	gold quality
nucleus accumbens	UBERON:0001882	77.10	gold quality
putamen	UBERON:0001874	76.70	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.19	gold quality
buccal mucosa cell	CL:0002336	74.38	gold quality
cingulate cortex	UBERON:0003027	74.15	gold quality
anterior cingulate cortex	UBERON:0009835	73.97	gold quality
right frontal lobe	UBERON:0002810	73.37	gold quality
spinal cord	UBERON:0002240	72.33	gold quality
amygdala	UBERON:0001876	71.69	gold quality
lower esophagus mucosa	UBERON:0035834	71.17	gold quality
skin of leg	UBERON:0001511	70.90	gold quality
left ovary	UBERON:0002119	70.40	gold quality
skin of abdomen	UBERON:0001416	70.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.03	gold quality
hypothalamus	UBERON:0001898	69.34	gold quality
ovary	UBERON:0000992	69.17	gold quality
choroid plexus epithelium	UBERON:0003911	68.78	silver quality
esophagus mucosa	UBERON:0002469	68.68	gold quality
right ovary	UBERON:0002118	68.65	gold quality
adenohypophysis	UBERON:0002196	68.58	gold quality
zone of skin	UBERON:0000014	68.47	gold quality
islet of Langerhans	UBERON:0000006	68.07	gold quality
prefrontal cortex	UBERON:0000451	67.90	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	551.86
E-GEOD-135922	yes	20.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MITF

miRNA regulators (miRDB)

19 targeting GPR143, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-4800-5P	97.22	65.91	324
HSA-MIR-3194-5P	96.80	64.90	1027
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-4509	96.19	65.80	900
HSA-MIR-627-5P	95.51	66.80	509
HSA-MIR-659-5P	95.36	65.00	300

Literature-anchored findings (GeneRIF, showing 40)

• Review: mutational analysis in ocular albinism type 1 (PMID:11793467)
• OA1 has been immunologically characterized as an antigen that is expressed, processed, and presented in an MHC-restricted fashion by melanoma cells, but for which there is the human equivalent of a “knockout”–i.e., complete deletion in a male patient. (PMID:12538723)
• Mutations in the OA1 gene is associated with ocular albinism (PMID:12868035)
• Mutational analysis of the OA1 ocular albinism gene. (PMID:16646960)
• No correlation was identified between congenital nystagmus and ocular albinism 1(OA1) gene. (PMID:16754205)
• Our results indicate that a mutation in the GPR143 gene can cause a variant form of ocular albinism, with congenital nystagmus as the most prominent and only consistent finding in all patients in this Chinese family. (PMID:17516023)
• eight new mutations located in the coding region of the gene are identified. (PMID:17822861)
• Two novel mutations in OA1 gene were identified in two families with ocular albinism. Identified mutations are likely loss-of-function mutations. Mutations in OA1 gene are associated with majority of X-linked ocular albinism cases. (PMID:17960122)
• These results indicate that this novel GPR143 mutation is associated with the congenital nystagmus observed in this Chinese family. (PMID:18523664)
• Panretinal function in OA1 is within normal limits at all ages, consistent with previous reports in generalized albinism. (PMID:18798082)
• L-DOPA activates GPR143 signaling through a Gq pathway, while dopamine inhibits the receptor. (PMID:18828673)
• Results illustrate an autocrine loop between OA1 and tyrosinase linked through L-DOPA, and this loop includes the secretion of at least one very potent retinal neurotrophic factor. (PMID:18828673)
• These results expand the mutation spectrum of GPR143, and demonstrate the clinical characteristics of OA1 among the Chinese. (PMID:18978956)
• The novel mutation p.G315X in the OA1 gene was identified in a Chinese family with ocular albinism, which is predicted to generate a premature stop codon. (PMID:19123159)
• Results suggest that this novel mutation in GPR143 is associated with the congenital nystagmus observed in this Chinese family. (PMID:19390656)
• Our results confirm that GPR143 is the major locus for X_linked ocular albinism and that exon 2 is a region of high susceptibility to deletions. (PMID:19604113)
• A Chinese family with X-linked ocular albinism and partial deletion of GPR143, is reported. (PMID:19610097)
• OA1 interacts with MART-1 at early stages of melanogenesis to control melanosome identity and composition. (PMID:19717472)
• we describe the first Spanish family known to present with X linked ocular albinism due to mutations in the OA1 gene (PMID:20649618)
• TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency. Clinical analysis revealed that the severity of the ocular manifestations depends on the degree of retinal pigmentation. (PMID:20861488)
• This is the first report of a Japanese X-linked ocular albinism (XLOA) patient with a GPR143 mutation. (PMID:21348135)
• A novel causative mutation of GPR143 was identified in a five-generation Chinese family with X-linked ocular albinism. (PMID:21423867)
• TYR gene mutations have a more severe effect on pigmentation than mutations in OCA2 and the GPR143 gene. Nevertheless, mutations in these genes affect the development of visual function either directly or by interaction with other genes like MC1R. (PMID:21541274)
• The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires endosomal sorting complex responsible for transport (ESCRT) function. (PMID:21730137)
• These results identify the Oa1 transducer Galphai3 as the first downstream component in the Oa1 signaling pathway. (PMID:21931697)
• Four patients with X-linked ocular albinism type 1 were identified from a cohort of 15 boys with clinical signs of albinism using mutation detection methods. (PMID:22486324)
• Data report that p.Y269X mutation of GPR143 gene is responsible for the pathogenesis of familial ocular albinism. (PMID:22916221)
• a novel splicing site mutation of the GPR143 gene was found in a Han Chinese congenital ocular albinism pedigree. (PMID:24301936)
• The GPR143 gene analysis identified an identical point mutation in two Ocular albinism 1 patients and their mothers . (PMID:24526317)
• Melanosome-autonomous regulation of size and number: the OA1 receptor sustains PMEL expression. (PMID:24650003)
• OA1 is involved in melanoma cell migration and that OA1induced melanoma cell migration is mediated through the RAS/RAF/MEK/ERK signaling pathway. (PMID:24736838)
• intronic mutation that creates a cryptic splice-donor site in GPR143 of patients with ocular albinism (PMID:26061757)
• Five mutations in GPR143 gene were detected in each of the five families, including a novel nonsense mutation of c.333G>A,two novel splicing mutations of c.360+1G>C and c.659-1G>A, a novel small deletion mutation of c.43_50dupGACGCAGC. (PMID:26160353)
• Here, we report a Chinese trio-family with the son who was affected by the X-linked ocular albinism in which a novel missense mutation in the GPR143 was observed. (PMID:26547501)
• Downstream signaling from GPR143 controls RPE secretion of pigment epithelium-derived factor (PEDF), a potent neurotrophic and antiangiogenic factor. (PMID:26741053)
• Twenty Chinese patients, including 15 sporadic IN cases and 5 from X-linked IN families, were recruited and underwent molecular genetic analysis. We first performed PCR-based DNA sequencing of the entire coding region and the splice junctions of the FRMD7 and GPR143 genes in participants. (PMID:27036142)
• This family was found to harbor a novel, likely pathogenic mutation in GPR143 resulting in a combined Stargart disease and heterozygous carrier phenotype in the affected sisters . (PMID:27367509)
• tyrosinase as a potential GPR143 binding protein opens new avenues for investigating the mechanisms that regulate pigmentation and neurogenesis. (PMID:27720922)
• Our results expand the spectrum of GPR143 mutations causing CN and further confirm the role of GPR143 in the pathogenesis of CN. (PMID:27958203)
• Three novel mutations, c.333_360+14del42insCTT, c.276G>A (p.W92X), and c.793C>T (p.R265X), were identified in GPR143 by PCR followed by Sanger sequencing in members of families with X-linked ocular albinism. (PMID:28211458)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr143	ENSDARG00000034572
mus_musculus	Gpr143	ENSMUSG00000025333
rattus_norvegicus	Gpr143	ENSRNOG00000003543

Protein

Protein identifiers

G-protein coupled receptor 143 — P51810 (reviewed: P51810)

Alternative names: Ocular albinism type 1 protein

All UniProt accessions (3): P51810, C9J9N1, H7BZN6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for tyrosine, L-DOPA and dopamine. After binding to L-DOPA, stimulates Ca(2+) influx into the cytoplasm, increases secretion of the neurotrophic factor SERPINF1 and relocalizes beta arrestin at the plasma membrane; this ligand-dependent signaling occurs through a G(q)-mediated pathway in melanocytic cells. Its activity is mediated by G proteins which activate the phosphoinositide signaling pathway. Also plays a role as an intracellular G protein-coupled receptor involved in melanosome biogenesis, organization and transport.

Subunit / interactions. Interacts with heterotrimeric G(i) proteins. Interacts with ARRB1 and ARRB2. Interacts with MLANA.

Subcellular location. Melanosome membrane. Lysosome membrane. Apical cell membrane.

Tissue specificity. Expressed at high levels in the retina, including the retinal pigment epithelium (RPE), and in melanocytes. Weak expression is observed in brain and adrenal gland.

Post-translational modifications. Glycosylated. Phosphorylated.

Disease relevance. Albinism ocular 1 (OA1) [MIM:300500] Form of albinism affecting only the eye. Pigment of the hair and skin is normal or only slightly diluted. Eyes may be severely affected with photophobia and reduced visual acuity. Nystagmus or strabismus are often associated. The irides and fundus are depigmented. The disease is caused by variants affecting the gene represented in this entry. Nystagmus 6, congenital, X-linked (NYS6) [MIM:300814] A form of nystagmus, a condition defined as conjugated, spontaneous and involuntary ocular oscillations that appear at birth or during the first three months of life. Other associated features may include mildly decreased visual acuity, strabismus, astigmatism, and occasionally head nodding. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The cytoplasmic domain 3 and the C-terminus tail domain contain the lysosomal sorting signals and are necessary and sufficient for intracellular retention and delivery to lysosomal and melanosomal, respectively in melanocytic and non-melanocytic cells.

Similarity. Belongs to the G-protein coupled receptor OA family.

RefSeq proteins (1): NP_000264* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001414	GPR143	Family

Pfam: PF02101

UniProt features (60 total): sequence variant 36, topological domain 8, transmembrane region 7, region of interest 2, short sequence motif 2, mutagenesis site 2, chain 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51810-F1	74.37	0.33

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): 106

Mutagenesis-validated functional residues (2):

Position	Phenotype
223–224	delivered to both at the cell surface and in vesicles of melanocytic and non-melanocytic cells. strongly delivered at th
329–330	mostly delivered at the cell surface of melanocytic and non-melanocytic cells. strongly delivered at the cell surface of

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-375280	Amine ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation

MSigDB gene sets: 144 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_PIGMENT_GRANULE_LOCALIZATION, GOBP_VESICLE_LOCALIZATION, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CELLULAR_PIGMENTATION, GOBP_PIGMENTATION, ONKEN_UVEAL_MELANOMA_UP, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_PIGMENT_METABOLIC_PROCESS, GOBP_PIGMENT_GRANULE_ORGANIZATION, GOBP_DEVELOPMENTAL_PIGMENTATION, GOCC_APICAL_PLASMA_MEMBRANE, GOMF_PEPTIDE_RECEPTOR_ACTIVITY

GO Biological Process (11): eye pigment biosynthetic process (GO:0006726), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), visual perception (GO:0007601), melanosome localization (GO:0032400), melanosome transport (GO:0032402), melanosome organization (GO:0032438), regulation of melanosome transport (GO:1902908), regulation of melanosome organization (GO:1903056), neuropeptide signaling pathway (GO:0007218)

GO Molecular Function (6): G protein-coupled receptor activity (GO:0004930), dopamine binding (GO:0035240), L-DOPA receptor activity (GO:0035643), L-DOPA binding (GO:0072544), L-tyrosine binding (GO:0072545), protein binding (GO:0005515)

GO Cellular Component (12): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), nuclear body (GO:0016604), cell junction (GO:0030054), melanosome membrane (GO:0033162), melanosome (GO:0042470), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
G protein-coupled receptor signaling pathway	3
regulation of cellular process	2
cation binding	2
amino acid binding	2
carboxylic acid binding	2
eye pigment metabolic process	1
pigment biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
phospholipase C activator activity	1
sensory perception of light stimulus	1
pigment granule localization	1
melanosome localization	1
establishment of melanosome localization	1
pigment granule transport	1
pigment granule organization	1
melanosome transport	1
regulation of transport	1
melanosome organization	1
regulation of organelle organization	1
transmembrane signaling receptor activity	1
catecholamine binding	1
neuropeptide receptor activity	1
L-DOPA binding	1
modified amino acid binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR143	FRMD7	Q6ZUT3	923
GPR143	MLANA	Q16655	898
GPR143	SHROOM2	Q13796	878
GPR143	OCA2	Q04671	876
GPR143	TYR	P14679	853
GPR143	TYRP1	P17643	831
GPR143	PMEL	P40967	775
GPR143	SLC45A2	Q9UMX9	749
GPR143	MITF	O75030	710
GPR143	SLC24A5	Q71RS6	667
GPR143	OPN1LW	P04000	663
GPR143	DCT	P40126	663
GPR143	SLC38A8	A6NNN8	658
GPR143	NYX	Q9GZU5	654
GPR143	LRMDA	Q9H2I8	620

IntAct

24 interactions, top by confidence:

A	B	Type	Score
GPR143	TYR	psi-mi:“MI:0915”(physical association)	0.520
GPR143	TYR	psi-mi:“MI:0403”(colocalization)	0.520
TYR	GPR143	psi-mi:“MI:2364”(proximity)	0.520
MLANA	GPR143	psi-mi:“MI:0915”(physical association)	0.460
GPR143	MLANA	psi-mi:“MI:0403”(colocalization)	0.460
Tyr	GPR143	psi-mi:“MI:0915”(physical association)	0.460
GPR143	Tyr	psi-mi:“MI:0403”(colocalization)	0.460
GPR143		psi-mi:“MI:0915”(physical association)	0.400
GPR143	Hgs	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	GPR143	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR143	psi-mi:“MI:0915”(physical association)	0.400
GPR143	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
GPR143	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
DRD2	GPR143	psi-mi:“MI:2364”(proximity)	0.380
DRD3	GPR143	psi-mi:“MI:2364”(proximity)	0.380
DRD3	GPR143	psi-mi:“MI:0403”(colocalization)	0.380
DRD2	GPR143	psi-mi:“MI:0403”(colocalization)	0.380

BioGRID (5): GNAI1 (Affinity Capture-Western), SUCLG2 (Affinity Capture-Western), SUCLG2 (Reconstituted Complex), GNAI1 (Reconstituted Complex), GPR143 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1L272, A2RV80, A4IF30, A6QL92, A6QPI1, O02777, O80605, P17200, P20272, P21554, P47746, P51810, P56971, P70259, Q1LZI2, Q2V4F9, Q3TDN0, Q3UGM2, Q4R794, Q5F383, Q5FVJ3, Q5IS73, Q5R4D7, Q5R6J3, Q5RD30, Q66H88, Q6P0E8, Q6P499, Q6R5J2, Q71SP5, Q8BGN5, Q8BZK4, Q8CBH5, Q8IY50, Q8NA31, Q8NBV4, Q8R314, Q8RWF4, Q8WV83, Q91WB2

Diamond homologs: P51810, P70259

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	94
Likely pathogenic	30
Uncertain significance	172
Likely benign	97
Benign	29

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
10514	NM_000273.3(GPR143):c.933_934dup (p.Gly312fs)	Pathogenic
10518	NM_000273.3(GPR143):c.695C>A (p.Thr232Lys)	Pathogenic
10519	NM_000273.3(GPR143):c.397T>A (p.Trp133Arg)	Pathogenic
10521	NM_000273.3(GPR143):c.104G>A (p.Gly35Asp)	Pathogenic
10522	NM_000273.3(GPR143):c.266C>T (p.Ser89Phe)	Pathogenic
10524	NM_000273.3(GPR143):c.162_198del (p.Ala55fs)	Pathogenic
10525	NM_000273.3(GPR143):c.231_249dup (p.Gly84fs)	Pathogenic
1184536	NM_000273.3(GPR143):c.346T>G (p.Cys116Gly)	Pathogenic
1202474	NM_000273.3(GPR143):c.394T>C (p.Trp132Arg)	Pathogenic
1213999	NM_000273.3(GPR143):c.361-2A>C	Pathogenic
1308636	NM_000273.3(GPR143):c.360+2T>C	Pathogenic
1323033	NM_000273.3(GPR143):c.73C>T (p.Gln25Ter)	Pathogenic
1338323	NM_000273.3(GPR143):c.886-2A>T	Pathogenic
1338413	NM_000273.3(GPR143):c.256_257delinsA (p.Val86fs)	Pathogenic
1352731	NM_000273.3(GPR143):c.733C>T (p.Arg245Ter)	Pathogenic
1359642	NM_000273.3(GPR143):c.878_885+2del	Pathogenic
1375183	NM_000273.3(GPR143):c.682C>T (p.Gln228Ter)	Pathogenic
1378551	NM_000273.3(GPR143):c.237_239del (p.Leu80del)	Pathogenic
1402320	NC_000023.10:g.(?9707505)(9733857_?)del	Pathogenic
1408135	NM_000273.3(GPR143):c.885+748G>A	Pathogenic
1409162	NM_000273.3(GPR143):c.552dup (p.Glu185Ter)	Pathogenic
1428544	NM_000273.3(GPR143):c.231_249del (p.Cys77fs)	Pathogenic
1435742	NM_000273.3(GPR143):c.187_188del (p.Ser63fs)	Pathogenic
1437914	NM_000273.3(GPR143):c.597C>A (p.Tyr199Ter)	Pathogenic
1451867	NM_000273.3(GPR143):c.442del (p.Ser148fs)	Pathogenic
1452017	NM_000273.3(GPR143):c.1A>G (p.Met1Val)	Pathogenic
1452428	NM_000273.3(GPR143):c.126_132del (p.Leu43fs)	Pathogenic
1454817	NC_000023.10:g.(?9707505)(9728886_?)del	Pathogenic
1455484	NM_000273.3(GPR143):c.52_59dup (p.Val21fs)	Pathogenic
1457365	NC_000023.10:g.(?9679631)(9716726_?)del	Pathogenic

SpliceAI

1689 predictions. Top by Δscore:

Variant	Effect	Δscore
X:9746149:CACAC:C	acceptor_gain	1.0000
X:9746151:CAC:C	acceptor_gain	1.0000
X:9746154:C:CA	acceptor_loss	1.0000
X:9746154:C:CC	acceptor_gain	1.0000
X:9746155:T:A	acceptor_loss	1.0000
X:9747939:T:TA	donor_gain	1.0000
X:9739632:T:A	donor_gain	0.9900
X:9741452:CCAA:C	acceptor_gain	0.9900
X:9741453:CAAC:C	acceptor_gain	0.9900
X:9746039:TTTAC:T	donor_loss	0.9900
X:9746040:TTA:T	donor_loss	0.9900
X:9746041:TA:T	donor_loss	0.9900
X:9746042:A:AG	donor_loss	0.9900
X:9746150:ACAC:A	acceptor_gain	0.9900
X:9746151:CACC:C	acceptor_gain	0.9900
X:9747577:C:CA	donor_gain	0.9900
X:9748569:CTT:C	donor_loss	0.9900
X:9748570:TTACC:T	donor_loss	0.9900
X:9748571:T:TG	donor_loss	0.9900
X:9748572:A:T	donor_loss	0.9900
X:9739716:TTCC:T	acceptor_gain	0.9800
X:9741456:C:CC	acceptor_gain	0.9800
X:9743573:TAAA:T	donor_gain	0.9800
X:9743574:AAAA:A	donor_gain	0.9800
X:9747940:C:A	donor_gain	0.9800
X:9748568:ACTT:A	donor_loss	0.9800
X:9748662:TGGTG:T	acceptor_gain	0.9800
X:9748667:C:CC	acceptor_gain	0.9800
X:9760715:A:AC	donor_gain	0.9800
X:9760716:C:CC	donor_gain	0.9800

AlphaMissense

2597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:9759423:A:G	W122R	0.980
X:9759423:A:T	W122R	0.980
X:9760720:A:C	S119R	0.971
X:9760720:A:T	S119R	0.971
X:9760722:T:G	S119R	0.971
X:9741349:A:G	W292R	0.970
X:9741349:A:T	W292R	0.970
X:9759390:A:G	W133R	0.966
X:9759390:A:T	W133R	0.966
X:9759393:A:G	W132R	0.965
X:9759393:A:T	W132R	0.965
X:9743624:C:A	R236S	0.963
X:9743624:C:G	R236S	0.963
X:9741443:A:C	N260K	0.962
X:9741443:A:T	N260K	0.962
X:9743628:T:A	E235V	0.962
X:9765568:C:G	G84R	0.962
X:9741428:G:C	S265R	0.960
X:9741428:G:T	S265R	0.960
X:9741430:T:G	S265R	0.960
X:9748638:A:G	W162R	0.960
X:9748638:A:T	W162R	0.960
X:9743657:T:A	K225N	0.958
X:9743657:T:G	K225N	0.958
X:9765577:C:G	G81R	0.957
X:9743594:A:C	F246L	0.954
X:9743594:A:T	F246L	0.954
X:9743596:A:G	F246L	0.954
X:9739708:A:C	N299K	0.952
X:9739708:A:T	N299K	0.952

dbSNP variants (sampled 300 via entrez): RS1000125540 (X:9752933 G>C), RS1000139266 (X:9727775 C>T), RS1000307547 (X:9774837 A>C,G), RS1000355534 (X:9775024 C>T), RS1000422886 (X:9766597 A>C), RS1000449304 (X:9733074 G>A), RS1000451125 (X:9736873 A>T), RS1000537584 (X:9760185 G>A,T), RS1000732689 (X:9729460 G>C), RS1000800641 (X:9732365 C>T), RS1000868156 (X:9741871 G>C,T), RS1000887524 (X:9753505 G>T), RS1000919730 (X:9766913 A>T), RS1000937472 (X:9743047 C>T), RS1001022644 (X:9764423 A>C)

Disease associations

OMIM: gene MIM:300808 | disease phenotypes: MIM:300814, MIM:300500, MIM:310700, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
ocular albinism	Definitive	X-linked
X-linked recessive ocular albinism	Strong	X-linked
nystagmus 6, congenital, X-linked	Strong	X-linked
GPR143-related foveal hypoplasia	Strong	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
GPR143-related foveal hypoplasia	Definitive	XL

Mondo (9): nystagmus 6, congenital, X-linked (MONDO:0010435), X-linked recessive ocular albinism (MONDO:0021019), retinal disorder (MONDO:0005283), GPR143-related foveal hypoplasia (MONDO:0700230), pathologic nystagmus (MONDO:0004843), ocular albinism (MONDO:0017304), congenital nystagmus (MONDO:0005712), albinism (MONDO:0043209), autism (MONDO:0005260)

Orphanet (3): X-linked recessive ocular albinism (Orphanet:54), Ocular albinism (Orphanet:284804), NON RARE IN EUROPE: Idiopathic infantile nystagmus (Orphanet:651)

HPO phenotypes

23 total (24 of 23 shown, HPO-id order):

HPO	Term
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000545	Myopia
HP:0000613	Photophobia
HP:0000615	Abnormal pupil morphology
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000666	Horizontal nystagmus
HP:0001103	Abnormal macular morphology
HP:0001107	Ocular albinism
HP:0001361	Nystagmus-induced head nodding
HP:0001417	X-linked inheritance
HP:0001419	X-linked recessive inheritance
HP:0001480	Freckling
HP:0003593	Infantile onset
HP:0005592	Giant melanosomes in melanocytes
HP:0007663	Reduced visual acuity
HP:0007730	Iris hypopigmentation
HP:0007750	Hypoplasia of the fovea
HP:0007814	Retinal pigment epithelial mottling
HP:0007894	Fundus hypopigmentation
HP:0008069	Neoplasm of the skin
HP:0000717	Autism

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001942_23	Prostate cancer	2.000000e-10

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D000417	Albinism	C11.270.040; C16.320.290.040; C16.320.565.100.102; C16.320.850.080; C17.800.621.440.102; C17.800.827.080; C18.452.648.100.102
D016117	Albinism, Ocular	C11.270.040.090; C16.320.290.040.090; C16.320.565.100.102.090; C16.320.850.080.090; C17.800.621.440.102.090; C17.800.827.080.090; C18.452.648.100.102.090
D001321	Autistic Disorder	F03.625.164.113.500
D020417	Nystagmus, Congenital	C10.292.562.675.300; C11.590.400.300; C16.614.643
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D012164	Retinal Diseases	C11.768
C537863	Ocular Albinism type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523867 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — GPR143

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	4
entinostat	increases expression, affects cotreatment	2
FR900359	increases phosphorylation	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
arsenite	decreases methylation	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	decreases expression	1
Sunitinib	decreases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Isotretinoin	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883413	Binding	PRESTO-Tango GPCRome screening (GPR143)	Data for DCP probe UCSF924

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_KX35	PathHunter CHO-K1 GPR143 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_UJ70	SEIi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism