XPR1

Summary

XPR1 (xenotropic and polytropic retrovirus receptor 1, HGNC:12827) is a protein-coding gene on chromosome 1q25.3, encoding Solute carrier family 53 member 1 (Q9UBH6). Inorganic ion transporter that mediates phosphate ion export across the plasma membrane.

The protein encoded by this gene is a receptor for the xenotropic and polytropic classes of murine leukemia viruses. The encoded protein is involved in phosphate homeostasis by mediating phosphate export from the cell. Defects in this gene have been associated with idiopathic basal ganglia calcification-6.

Source: NCBI Gene 9213 — RefSeq curated summary.

At a glance

• Gene–disease (curated): basal ganglia calcification, idiopathic, 6 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 332 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 56
• MANE Select transcript: NM_004736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12827
Approved symbol	XPR1
Name	xenotropic and polytropic retrovirus receptor 1
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Aliases	SYG1, X3, SLC53A1
Ensembl gene	ENSG00000143324
Ensembl biotype	protein_coding
OMIM	605237
Entrez	9213

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000367589, ENST00000367590, ENST00000464817, ENST00000467345, ENST00000498177, ENST00000876515, ENST00000876516, ENST00000876517, ENST00000876518, ENST00000876519, ENST00000919103, ENST00000919104, ENST00000919105, ENST00000948817

RefSeq mRNA: 3 — MANE Select: NM_004736 NM_001135669, NM_001328662, NM_004736

CCDS: CCDS1340, CCDS44284

Canonical transcript exons

ENST00000367590 — 15 exons

Exon	Start	End
ENSE00000959295	180682360	180682411
ENSE00001068585	180880076	180880297
ENSE00001068587	180825165	180825344
ENSE00001068589	180836522	180836716
ENSE00001068591	180806062	180806211
ENSE00001068592	180787753	180787854
ENSE00001068593	180824753	180824943
ENSE00001068594	180803388	180803611
ENSE00001068595	180811407	180811488
ENSE00001068596	180806474	180806557
ENSE00001068597	180834874	180835045
ENSE00001357825	180632022	180632270
ENSE00001421985	180884006	180890279
ENSE00003549395	180873803	180873942
ENSE00003600605	180863708	180863874

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.8102 / max 283.3729, expressed in 1798 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6961	9.5148	1761
6962	1.8128	724
6963	1.4764	638
6964	1.3795	821
6965	0.6267	293

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.16	gold quality
kidney epithelium	UBERON:0004819	98.19	gold quality
left ventricle myocardium	UBERON:0006566	97.40	gold quality
ganglionic eminence	UBERON:0004023	96.49	gold quality
secondary oocyte	CL:0000655	96.15	gold quality
endothelial cell	CL:0000115	96.09	silver quality
nasal cavity epithelium	UBERON:0005384	95.50	gold quality
myocardium	UBERON:0002349	95.04	gold quality
epithelial cell of pancreas	CL:0000083	94.85	gold quality
oocyte	CL:0000023	94.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.41	silver quality
islet of Langerhans	UBERON:0000006	94.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.75	gold quality
heart right ventricle	UBERON:0002080	93.27	gold quality
ileal mucosa	UBERON:0000331	92.32	gold quality
ventricular zone	UBERON:0003053	91.64	gold quality
endometrium	UBERON:0001295	91.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.96	gold quality
middle temporal gyrus	UBERON:0002771	90.88	gold quality
bronchial epithelial cell	CL:0002328	90.71	gold quality
bronchus	UBERON:0002185	90.62	gold quality
tibia	UBERON:0000979	90.09	gold quality
renal medulla	UBERON:0000362	89.91	gold quality
visceral pleura	UBERON:0002401	89.63	gold quality
trachea	UBERON:0003126	89.49	gold quality
caput epididymis	UBERON:0004358	89.10	gold quality
corpus epididymis	UBERON:0004359	88.97	gold quality
germinal epithelium of ovary	UBERON:0001304	88.93	gold quality
seminal vesicle	UBERON:0000998	88.92	gold quality
vena cava	UBERON:0004087	88.74	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	1410.43
E-HCAD-5	yes	43.83
E-ANND-3	yes	8.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, NR0B2, POU1F1

miRNA regulators (miRDB)

235 targeting XPR1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 14)

• These studies suggest that the expression of Xpr1 and certain genotypes of the RNASEL gene, which could restrict XMRV infection, may play important roles in defining XMRV tropisms in certain cell types. (PMID:20410264)
• XPR1 mutations alter phosphate export and phosphate homeostasis in primary familial brain calcification. (PMID:25938945)
• These results confirm that loss of XPR1-mediated phosphate export function causes primary familial brain calcification, occurring in less than 8 % of cases negative for the other genes, and may be responsible for parkinsonism. (PMID:27230854)
• These findings uncover a critical role of XPR1 in tongue squamous cell carcinoma (TSCC) progression via activation of NF-kappaB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target. (PMID:30995931)
• Characterization of XPR1/SLC53A1 variants located outside of the SPX domain in patients with primary familial brain calcification. (PMID:31043717)
• conclude that IP6K1 and -2 together control inositol pyrophosphate metabolism and thereby physiologically regulate phosphate export and other aspects of mammalian cellular phosphate homeostasis (PMID:31186349)
• XPR1 activity was regulated by a member of the inositol pyrophosphate (PP-InsP) signaling family: 1,5-bis-diphosphoinositol 2,3,4,6-tetrakisphosphate (InsP8). (PMID:32019887)
• Interplay between primary familial brain calcification-associated SLC20A2 and XPR1 phosphate transporters requires inositol polyphosphates for control of cellular phosphate homeostasis. (PMID:32393577)
• The genetic polymorphisms of XPR1 and SCL34A3 are associated with Fanconi syndrome in Chinese patients of tumor-induced osteomalacia. (PMID:32725396)
• Circ-XPR1 promotes osteosarcoma proliferation through regulating the miR-214-5p/DDX5 axis. (PMID:32920730)
• Clinical implication of xenotropic and polytropic retrovirus receptor 1 in papillary thyroid carcinoma. (PMID:34117845)
• The miR-4732-5p/XPR1 axis suppresses the invasion, metastasis, and epithelial-mesenchymal transition of lung adenocarcinoma via the PI3K/Akt/GSK3beta/Snail pathway. (PMID:35388387)
• Phosphate dysregulation via the XPR1-KIDINS220 protein complex is a therapeutic vulnerability in ovarian cancer. (PMID:35437317)
• Human XPR1 structures reveal phosphate export mechanism. (PMID:39169184)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	xpr1a	ENSDARG00000062449
mus_musculus	Xpr1	ENSMUSG00000026469
rattus_norvegicus	Xpr1	ENSRNOG00000000042
caenorhabditis_elegans		WBGENE00012659

Protein

Protein identifiers

Solute carrier family 53 member 1 — Q9UBH6 (reviewed: Q9UBH6)

Alternative names: Phosphate exporter SLC53A1, Protein SYG1 homolog, Xenotropic and polytropic murine leukemia virus receptor X3, Xenotropic and polytropic retrovirus receptor 1

All UniProt accessions (1): Q9UBH6

UniProt curated annotations — full annotation on UniProt →

Function. Inorganic ion transporter that mediates phosphate ion export across the plasma membrane. Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling. Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), which are important intracellular signaling molecules involved in regulation of phosphate flux.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed. Detected in spleen, lymph node, thymus, leukocytes, bone marrow, heart, kidney, pancreas and skeletal muscle.

Disease relevance. Basal ganglia calcification, idiopathic, 6 (IBGC6) [MIM:616413] A form of basal ganglia calcification, an autosomal dominant condition characterized by symmetric calcification in the basal ganglia and other brain regions. Affected individuals can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, seizures, and chronic headache. Serum levels of calcium, phosphate, alkaline phosphatase and parathyroid hormone are normal. The neuropathological hallmark of the disease is vascular and pericapillary calcification, mainly of calcium phosphate, in the affected brain areas. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosterically activated by inositol hexakisphosphate (Ins6P).

Domain organisation. The SPX domain plays a role in the regulation of phosphate flux. Inositol hexakisphosphate (Ins6P) is bound between two SPX domains of the homodimer. The SPX domain has high affinity for inositol polyphosphates and its affinity for inorganic phosphate is two to three orders of magnitude lower.

Similarity. Belongs to the SYG1 (TC 2.A.94) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBH6-1	1	yes
Q9UBH6-2	2

RefSeq proteins (3): NP_001129141, NP_001315591, NP_004727* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004331	SPX_dom	Domain
IPR004342	EXS_C	Domain

Pfam: PF03105, PF03124

Catalyzed reactions (Rhea), 1 shown:

• phosphate(in) = phosphate(out) (RHEA:32823)

UniProt features (120 total): mutagenesis site 33, helix 25, topological domain 11, transmembrane region 10, turn 9, sequence variant 8, strand 7, binding site 7, domain 2, region of interest 2, modified residue 2, chain 1, site 1, splice variant 1, intramembrane region 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8TYU	X-RAY DIFFRACTION	1.4
8TYV	X-RAY DIFFRACTION	1.85
9CL0	ELECTRON MICROSCOPY	2.3
5IJH	X-RAY DIFFRACTION	2.43
9DVJ	ELECTRON MICROSCOPY	2.52
9IJY	ELECTRON MICROSCOPY	2.64
9DVN	ELECTRON MICROSCOPY	2.75
9DVP	ELECTRON MICROSCOPY	2.81
8X5B	ELECTRON MICROSCOPY	2.84
9IWS	ELECTRON MICROSCOPY	2.86
9J4X	ELECTRON MICROSCOPY	2.9
9IJZ	ELECTRON MICROSCOPY	2.91
9DVM	ELECTRON MICROSCOPY	2.92
8X5F	ELECTRON MICROSCOPY	2.96
9DVL	ELECTRON MICROSCOPY	2.97
9ITG	ELECTRON MICROSCOPY	3.03
9DVK	ELECTRON MICROSCOPY	3.06
9DVO	ELECTRON MICROSCOPY	3.1
9J51	ELECTRON MICROSCOPY	3.1
9J52	ELECTRON MICROSCOPY	3.1
9JXN	ELECTRON MICROSCOPY	3.12
9JXH	ELECTRON MICROSCOPY	3.15
9JXJ	ELECTRON MICROSCOPY	3.22
9JXL	ELECTRON MICROSCOPY	3.23
9JXD	ELECTRON MICROSCOPY	3.29
9J53	ELECTRON MICROSCOPY	3.3
9J97	ELECTRON MICROSCOPY	3.3
9JXI	ELECTRON MICROSCOPY	3.31
9INE	ELECTRON MICROSCOPY	3.32
9J98	ELECTRON MICROSCOPY	3.33

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBH6-F1	84.31	0.58

Functional residue map

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

Catalytic / active sites (1): 573 (gating residue for phosphate transport)

Ligand- & substrate-binding residues (7): 398; 401; 482; 483; 570; 603; 604

Post-translational modifications (2): 668, 690

Mutagenesis-validated functional residues (33):

Position	Phenotype
22	decreases phosphate efflux.
158	decreases phosphate efflux. decreases phosphate efflux; when associated with a-161 and a-165.
161	decreases phosphate efflux; when associated with a-158 and a-165.
165	decreases phosphate efflux; when associated with a-158 and a-161.
211	increases phosphate efflux; when associated with e-219.
219	increases phosphate efflux; when associated with e-211.
235	decreases phosphate efflux.
238	monomeric; decreases phosphate efflux.
239	decreases phosphate efflux.
242	monomeric; decreases phosphate efflux.
270	decreases phosphate efflux.
273	decreases phosphate efflux.
394	increases phosphate efflux.
398	decreases phosphate efflux.
401	decreases phosphate efflux.
448	decreases phosphate efflux.
452	decreases phosphate efflux.
459	decreases phosphate efflux.
466	increases phosphate efflux.
482	decreases phosphate efflux.
483	decreases phosphate efflux.
497	decreases phosphate efflux. decreases phosphate efflux; when associated with c-582.
533	decreases phosphate efflux.
570	decreases phosphate efflux.
573	decreases phosphate efflux.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 335 (showing top): TAATAAT_MIR126, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_511, GOBP_INORGANIC_ANION_TRANSPORT, TGACCTY_ERR1_Q2, CAGCTG_AP4_Q5, PATIL_LIVER_CANCER, GATA3_01, NF1_Q6_01, GOBP_PHOSPHATE_ION_TRANSPORT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP

GO Biological Process (6): phosphate ion transport (GO:0006817), response to virus (GO:0009615), cellular response to phosphate starvation (GO:0016036), intracellular phosphate ion homeostasis (GO:0030643), phosphate ion transmembrane transport (GO:0035435), symbiont entry into host cell (GO:0046718)

GO Molecular Function (4): inositol hexakisphosphate binding (GO:0000822), virus receptor activity (GO:0001618), phosphate transmembrane transporter activity (GO:0005315), efflux transmembrane transporter activity (GO:0015562)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
inorganic anion transport	1
response to other organism	1
cellular response to starvation	1
phosphate ion homeostasis	1
intracellular chemical homeostasis	1
phosphate ion transport	1
transmembrane transport	1
viral life cycle	1
symbiont entry into host	1
anion binding	1
alcohol binding	1
symbiont entry into host cell	1
exogenous protein binding	1
secondary active transmembrane transporter activity	1
transmembrane transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XPR1	PPARG	P37231	996
XPR1	NR1H4	Q96RI1	990
XPR1	PPARA	Q07869	970
XPR1	ABCA1	O95477	939
XPR1	NR1H2	P55055	932
XPR1	ABCG5	Q9H222	918
XPR1	SREBF2	Q12772	914
XPR1	ABCG8	Q9H221	901
XPR1	MYLIP	Q8WY64	896
XPR1	SLC20A2	Q08357	892
XPR1	NR1I2	O75469	889
XPR1	NR1H3	Q13133	885
XPR1	CYP7A1	P22680	884
XPR1	ABCG1	P45844	873
XPR1	SREBF1	P36956	852

IntAct

99 interactions, top by confidence:

A	B	Type	Score
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
CD226	MEN1	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
VSIG1	TNPO2	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
RHOT2	UBC	psi-mi:“MI:0914”(association)	0.530
XPR1	MYORG	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
TACC3	DHRS2	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Rab5c		psi-mi:“MI:0914”(association)	0.350
Rmdn3	DERL1	psi-mi:“MI:0914”(association)	0.350
Flot1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Actb		psi-mi:“MI:0914”(association)	0.350
RAB5C	GCA	psi-mi:“MI:0914”(association)	0.350

BioGRID (268): XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS), XPR1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNC1, A2VE61, A7XZ53, B1H3H9, D3ZEH5, F4HXY7, O35052, O95674, P48651, P98191, Q00576, Q01685, Q0JR55, Q0VCK9, Q28CY9, Q28H54, Q2KHY9, Q5EA65, Q5N8Q3, Q5R7B1, Q5U239, Q5ZKD1, Q5ZKJ0, Q5ZM65, Q6AXM5, Q6DD44, Q6DED0, Q6I628, Q7ZYQ3, Q803C9, Q8BGS7, Q8BXA5, Q8CIF6, Q8NBJ9, Q91XU8, Q91ZQ0, Q92903, Q96KA5, Q99KU0, Q99L43

Diamond homologs: A7XZ53, A8DZH4, P16151, Q28CY9, Q54G02, Q54MJ9, Q55B06, Q651J5, Q657S5, Q6DD44, Q6K991, Q6R8G2, Q6R8G3, Q6R8G4, Q6R8G5, Q6R8G6, Q6R8G7, Q6R8G8, Q8S403, Q93ZF5, Q9LJW0, Q9QZ70, Q9QZ71, Q9R031, Q9R032, Q9TU72, Q9UBH6, Q9VRR2, Q9Z0U0, P41771, Q6R8G0, P40528, O59712

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 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
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	5	25.2×	4e-04
Negative regulation of MAPK pathway	5	15.8×	2e-03
Defective CFTR causes cystic fibrosis	5	13.1×	4e-03
Signaling by ALK fusions and activated point mutants	7	12.5×	4e-04
Regulation of RAS by GAPs	5	11.5×	4e-03
E3 ubiquitin ligases ubiquitinate target proteins	5	11.5×	4e-03
Clathrin-mediated endocytosis	7	7.1×	4e-03
RAF/MAP kinase cascade	7	5.1×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
axonogenesis	7	10.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	148
Likely benign	106
Benign	50

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
192303	NM_004736.4(XPR1):c.434T>C (p.Leu145Pro)	Pathogenic
192304	NM_004736.4(XPR1):c.407G>A (p.Ser136Asn)	Pathogenic
192305	NM_004736.4(XPR1):c.419T>C (p.Leu140Pro)	Pathogenic
192306	NM_004736.4(XPR1):c.653T>C (p.Leu218Ser)	Pathogenic
3065743	NM_004736.4(XPR1):c.863A>G (p.Asn288Ser)	Likely pathogenic
3337748	NM_004736.4(XPR1):c.1375C>T (p.Arg459Cys)	Likely pathogenic
806294	NM_004736.4(XPR1):c.2031-2A>G	Likely pathogenic

SpliceAI

3617 predictions. Top by Δscore:

Variant	Effect	Δscore
1:180682355:AATAG:A	acceptor_gain	1.0000
1:180682357:TAG:T	acceptor_loss	1.0000
1:180682358:A:AG	acceptor_gain	1.0000
1:180682358:AG:A	acceptor_gain	1.0000
1:180682358:AGGCT:A	acceptor_loss	1.0000
1:180682359:G:GG	acceptor_gain	1.0000
1:180682359:GG:G	acceptor_gain	1.0000
1:180682359:GGC:G	acceptor_gain	1.0000
1:180682409:AAGG:A	donor_loss	1.0000
1:180682411:GGT:G	donor_loss	1.0000
1:180682413:T:G	donor_loss	1.0000
1:180705295:C:G	donor_gain	1.0000
1:180705339:G:GT	donor_gain	1.0000
1:180705340:A:T	donor_gain	1.0000
1:180787743:T:TA	acceptor_gain	1.0000
1:180787751:A:AG	acceptor_gain	1.0000
1:180787752:G:GT	acceptor_gain	1.0000
1:180787752:GT:G	acceptor_gain	1.0000
1:180787752:GTT:G	acceptor_gain	1.0000
1:180787752:GTTA:G	acceptor_gain	1.0000
1:180787752:GTTAC:G	acceptor_gain	1.0000
1:180787850:TTCAG:T	donor_gain	1.0000
1:180787851:TCAG:T	donor_gain	1.0000
1:180787852:CAG:C	donor_gain	1.0000
1:180787853:AG:A	donor_gain	1.0000
1:180787854:GG:G	donor_gain	1.0000
1:180787855:G:GG	donor_gain	1.0000
1:180803385:TA:T	acceptor_loss	1.0000
1:180803386:A:AC	acceptor_loss	1.0000
1:180803386:A:AG	acceptor_gain	1.0000

AlphaMissense

4590 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:180632208:T:C	F3L	1.000
1:180632209:T:C	F3S	1.000
1:180632209:T:G	F3C	1.000
1:180632210:C:A	F3L	1.000
1:180632210:C:G	F3L	1.000
1:180632241:G:A	E14K	1.000
1:180632243:G:C	E14D	1.000
1:180632243:G:T	E14D	1.000
1:180632244:T:A	W15R	1.000
1:180632244:T:C	W15R	1.000
1:180632245:G:C	W15S	1.000
1:180632246:G:C	W15C	1.000
1:180632246:G:T	W15C	1.000
1:180632256:T:C	Y19H	1.000
1:180632265:T:C	Y22H	1.000
1:180632266:A:G	Y22C	1.000
1:180682368:G:C	K26N	1.000
1:180682368:G:T	K26N	1.000
1:180787828:T:C	L66P	1.000
1:180787845:T:C	F72L	1.000
1:180787847:T:A	F72L	1.000
1:180787847:T:G	F72L	1.000
1:180803394:T:C	L77P	1.000
1:180803402:G:C	A80P	1.000
1:180803424:T:C	L87P	1.000
1:180803556:T:C	L131P	1.000
1:180803579:T:G	Y139D	1.000
1:180803583:T:C	L140P	1.000
1:180803589:T:C	L142P	1.000
1:180803595:T:C	L144P	1.000

dbSNP variants (sampled 300 via entrez): RS1000005126 (1:180726587 G>A,C), RS1000009890 (1:180737793 C>T), RS1000013434 (1:180744398 T>C,G), RS1000020720 (1:180860637 C>T), RS1000039408 (1:180817516 T>C), RS1000066952 (1:180680715 T>C), RS1000068063 (1:180695030 C>T), RS1000093352 (1:180837590 T>G), RS1000095378 (1:180673425 T>C), RS1000110114 (1:180632428 C>G), RS1000114009 (1:180787023 A>G,T), RS1000118593 (1:180868494 C>T), RS1000119863 (1:180694817 A>C), RS1000178099 (1:180632097 A>G,T), RS1000179708 (1:180718439 A>C)

Disease associations

OMIM: gene MIM:605237 | disease phenotypes: MIM:616413

GenCC curated gene-disease

Disease	Classification	Inheritance
basal ganglia calcification, idiopathic, 6	Strong	Autosomal dominant
bilateral striopallidodentate calcinosis	Supportive	Autosomal dominant

Mondo (2): basal ganglia calcification, idiopathic, 6 (MONDO:0014628), bilateral striopallidodentate calcinosis (MONDO:0008947)

Orphanet (1): Bilateral striopallidodentate calcinosis (Orphanet:1980)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000298	Mask-like facies
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0000751	Personality changes
HP:0000802	Impotence
HP:0000822	Hypertension
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001268	Mental deterioration
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001350	Slurred speech
HP:0002015	Dysphagia
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002072	Chorea
HP:0002075	Dysdiadochokinesis
HP:0002135	Basal ganglia calcification
HP:0002172	Postural instability
HP:0002305	Athetosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002088_16	Asthma (childhood onset)	9.000000e-06
GCST006624_34	Systolic blood pressure	5.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536275	Fahr’s disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC53 Phosphate carriers

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
sodium arsenite	decreases expression, increases abundance, increases expression	3
Acetaminophen	decreases expression, increases expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
glycidyl methacrylate	decreases expression	1
salinomycin	decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Phosphates	affects export	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4RE	HCT116-XPR1-KO-c20	Cancer cell line	Male
CVCL_D4RF	HCT116-XPR1-KO-c9	Cancer cell line	Male
CVCL_TY38	HAP1 XPR1 (-) 1	Cancer cell line	Male
CVCL_TY39	HAP1 XPR1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05662111	PHASE2	RECRUITING	Treatment of Ectopic Calcification in Fahr’s Disease or Syndrome