MYORG

Summary

MYORG (myogenesis regulating glycosidase, HGNC:19918) is a protein-coding gene on chromosome 9p13.3, encoding Alpha-galactosidase MYORG (Q6NSJ0). Alpha-galactosidase with unusual specificity for the Gal-alpha1,4-Glc structure, whose in vivo substrate is still unknown.

Predicted to enable hydrolase activity, hydrolyzing O-glycosyl compounds. Involved in skeletal muscle fiber development. Predicted to be located in endoplasmic reticulum membrane and nuclear membrane. Implicated in basal ganglia calcification.

Source: NCBI Gene 57462 — RefSeq curated summary.

At a glance

• Gene–disease (curated): basal ganglia calcification, idiopathic, 7, autosomal recessive (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 300 total — 12 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 64
• MANE Select transcript: NM_020702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19918
Approved symbol	MYORG
Name	myogenesis regulating glycosidase
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	NET37
Ensembl gene	ENSG00000164976
Ensembl biotype	protein_coding
OMIM	618255
Entrez	57462

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000297625, ENST00000379142, ENST00000896633, ENST00000896634, ENST00000896635, ENST00000896636, ENST00000925134, ENST00000925135, ENST00000964326, ENST00000964327

RefSeq mRNA: 1 — MANE Select: NM_020702 NM_020702

CCDS: CCDS78391

Canonical transcript exons

ENST00000297625 — 2 exons

Exon	Start	End
ENSE00001089087	34366666	34373006
ENSE00001419648	34376793	34376898

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 91.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.1582 / max 114.9041, expressed in 1209 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100496	4.0290	1090
100495	2.6246	693
100497	0.1783	85
100499	0.1034	61
100500	0.0974	61
100494	0.0907	38
100498	0.0348	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	91.96	gold quality
gastrocnemius	UBERON:0001388	91.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.16	gold quality
muscle of leg	UBERON:0001383	90.69	gold quality
vastus lateralis	UBERON:0001379	90.18	silver quality
ileal mucosa	UBERON:0000331	89.74	gold quality
jejunal mucosa	UBERON:0000399	89.70	gold quality
quadriceps femoris	UBERON:0001377	89.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.28	silver quality
right lobe of liver	UBERON:0001114	87.58	gold quality
biceps brachii	UBERON:0001507	87.34	gold quality
putamen	UBERON:0001874	87.02	gold quality
nucleus accumbens	UBERON:0001882	87.01	gold quality
skeletal muscle tissue	UBERON:0001134	86.96	gold quality
mucosa of transverse colon	UBERON:0004991	86.88	gold quality
caudate nucleus	UBERON:0001873	86.86	gold quality
amygdala	UBERON:0001876	85.41	gold quality
transverse colon	UBERON:0001157	84.76	gold quality
ganglionic eminence	UBERON:0004023	84.69	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.49	gold quality
anterior cingulate cortex	UBERON:0009835	84.48	gold quality
muscle tissue	UBERON:0002385	84.37	gold quality
duodenum	UBERON:0002114	84.33	gold quality
rectum	UBERON:0001052	84.17	gold quality
liver	UBERON:0002107	83.90	gold quality
right frontal lobe	UBERON:0002810	83.82	gold quality
jejunum	UBERON:0002115	82.28	gold quality
body of stomach	UBERON:0001161	82.10	gold quality
colon	UBERON:0001155	82.01	gold quality
large intestine	UBERON:0000059	81.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

179 targeting MYORG, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1184	99.99	68.19	1458
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6499-3P	99.90	66.38	1212

Literature-anchored findings (GeneRIF, showing 12)

• Findings provide strong evidence that loss-of-function mutations of MYORG cause brain calcification in humans. Compound heterozygous or homozygous mutations of MYORG co-segregated completely with primary familial brain calcification in six families. (PMID:29910000)
• MYORG as a novel causative gene for primary familial brain calcification (PMID:30589467)
• A point mutation in MYORG is associated with primary familial brain calcification in a Turkish family. (PMID:30649222)
• MYORG mutations are linked to a recessive form of primary familial brain calcification. This association was recently described in patients of Chinese ancestry. Study suggests the possibility that MYORG mutations lead to calcification in a PDGFRbeta-related pathway. (PMID:30656188)
• analysis of a novel homozygous MYORG mutation in a consanguineous Italian family indicates that it may have a role in primary familial brain calcification as well as in brain calcifications of heterozygous carriers (PMID:30895394)
• that MYORG is a novel major primary familial brain calcification causative gene and that the phenotype associated with such mutations may be recognized based on pedigree (PMID:31009047)
• Primary familial brain calcification caused by MYORG mutations in an Italian family. (PMID:31621601)
• MYORG Mutation Heterozygosity Is Associated With Brain Calcification. (PMID:31951047)
• MYORG gene disease-causing variants in a family with primary familial brain calcification presenting with stroke-like episodes. (PMID:32896900)
• Paroxysmal Kinesigenic Dyskinesia Secondary to Brain Calcification with a Homozygous MYORG Mutation. (PMID:34346093)
• Fahr’s disease linked to a novel mutation in MYORG variants manifesting as paroxysmal limb stiffness and dysarthria: Case report and literature review. (PMID:37680026)
• Genetic and pathophysiological insights from autopsied patient with primary familial brain calcification: novel MYORG variants and astrocytic implications. (PMID:39180105)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	myorg	ENSDARG00000074894
danio_rerio	MYORG	ENSDARG00000104260
mus_musculus	Myorg	ENSMUSG00000046312
rattus_norvegicus	Myorg	ENSRNOG00000023208
drosophila_melanogaster	GCS2alpha	FBGN0027588
drosophila_melanogaster	tobi	FBGN0261575
caenorhabditis_elegans		WBGENE00018682
caenorhabditis_elegans		WBGENE00019895

Paralogs (6): GANAB (ENSG00000089597), SI (ENSG00000090402), GAA (ENSG00000171298), GANC (ENSG00000214013), MGAM (ENSG00000257335), MGAM2 (ENSG00000257743)

Protein

Protein identifiers

Alpha-galactosidase MYORG — Q6NSJ0 (reviewed: Q6NSJ0)

Alternative names: Myogenesis regulating glycosidase, Nuclear envelope transmembrane protein 37

All UniProt accessions (2): Q6NSJ0, X6RA92

UniProt curated annotations — full annotation on UniProt →

Function. Alpha-galactosidase with unusual specificity for the Gal-alpha1,4-Glc structure, whose in vivo substrate is still unknown. Promotes myogenesis by activating AKT signaling through the maturation and secretion of IGF2.

Subunit / interactions. Homodimer. Interacts with IGF2; this interaction is required for IGF2 secretion.

Subcellular location. Nucleus membrane. Endoplasmic reticulum membrane.

Post-translational modifications. N-glycosylated.

Disease relevance. Basal ganglia calcification, idiopathic, 7, autosomal recessive (IBGC7) [MIM:618317] A form of basal ganglia calcification, a genetically heterogeneous 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.

Similarity. Belongs to the glycosyl hydrolase 31 family.

RefSeq proteins (1): NP_065753* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000322	Glyco_hydro_31_TIM	Domain
IPR013780	Glyco_hydro_b	Homologous_superfamily
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR048395	Glyco_hydro_31_C	Domain
IPR050985	Alpha-glycosidase_related	Family

Pfam: PF01055, PF21365

UniProt features (119 total): strand 41, sequence variant 30, helix 21, binding site 8, glycosylation site 6, turn 4, topological domain 2, disulfide bond 2, active site 2, chain 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7QQH	X-RAY DIFFRACTION	2.25
7QQF	X-RAY DIFFRACTION	2.43
7QQG	X-RAY DIFFRACTION	2.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NSJ0-F1	90.50	0.81

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 (2): 463 (nucleophile); 520 (proton donor/acceptor)

Ligand- & substrate-binding residues (8): 461; 504; 517; 520; 213; 353; 354; 426

Disulfide bonds (2): 125–134, 158–284

Glycosylation sites (6): 240, 250, 346, 372, 398, 511

Mutagenesis-validated functional residues (1):

Position	Phenotype
463	does not change nuclear membrane localization. does not rescue the myogenetic defect induced by depletion of endogenous

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 218 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, UEDA_PERIFERAL_CLOCK, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_INSULIN_LIKE_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, chr9p13, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_MYOTUBE_DIFFERENTIATION

GO Biological Process (4): carbohydrate metabolic process (GO:0005975), positive regulation of insulin-like growth factor receptor signaling pathway (GO:0043568), skeletal muscle fiber development (GO:0048741), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)

GO Molecular Function (4): alpha-galactosidase activity (GO:0004557), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), nuclear membrane (GO:0031965), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle membrane	2
intracellular membrane-bounded organelle	2
primary metabolic process	1
positive regulation of signal transduction	1
regulation of insulin-like growth factor receptor signaling pathway	1
insulin-like growth factor receptor signaling pathway	1
skeletal muscle tissue development	1
myotube cell development	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
galactosidase activity	1
hydrolase activity, acting on glycosyl bonds	1
catalytic activity	1
hydrolase activity	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
nucleus	1
nuclear envelope	1
cytoplasm	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYORG	SLC20A2	Q08357	813
MYORG	PDGFB	P01127	637
MYORG	XPR1	Q9UBH6	610
MYORG	PDGFRB	P09619	592
MYORG	PLPP7	Q8NBV4	533
MYORG	FAM219A	Q8IW50	424
MYORG	OR6J1	Q8NGC5	420
MYORG	SPMIP6	Q8NCR6	374
MYORG	SPATA31F1	Q6ZU69	370
MYORG	CYP4F2	P78329	349
MYORG	LEMD2	Q8NC56	347
MYORG	AADACL3	Q5VUY0	343
MYORG	TMEM120A	Q9BXJ8	322
MYORG	RRP36	Q96EU6	316
MYORG	ARID3C	A6NKF2	315

IntAct

49 interactions, top by confidence:

A	B	Type	Score
LYPD3	SCAMP1	psi-mi:“MI:0914”(association)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
MYORG	HSPA5	psi-mi:“MI:0914”(association)	0.530
CLIP4	AMPH	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
XPR1	MYORG	psi-mi:“MI:0914”(association)	0.530
HFE	ADAM10	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
LYPD3	CLASP2	psi-mi:“MI:0914”(association)	0.350
SIAE	COCH	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	TMEM223	psi-mi:“MI:0914”(association)	0.350
AMIGO1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TNFRSF10C	SLC22A23	psi-mi:“MI:0914”(association)	0.350
BRICD5	POTEF	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
TMEM169	GPR89A	psi-mi:“MI:0914”(association)	0.350
LYPD3	TNPO2	psi-mi:“MI:0914”(association)	0.350
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): KIAA1161 (Affinity Capture-MS), KIAA1161 (Affinity Capture-MS), KIAA1161 (Affinity Capture-MS), KIAA1161 (Affinity Capture-MS), KIAA1161 (Affinity Capture-MS), KIAA1161 (Affinity Capture-MS), ASAP3 (Affinity Capture-MS), KIAA1161 (Affinity Capture-MS), DNAJA4 (Affinity Capture-MS), ENTPD7 (Affinity Capture-MS), PRPF38A (Affinity Capture-MS), KIAA1161 (Affinity Capture-MS), CGRRF1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), KIAA1161 (Affinity Capture-MS)

ESM2 similar proteins: A6NE02, A8MY62, A8T672, A8T677, A8T695, C9JR72, D3Z7H8, O08644, O15197, O19179, O62763, O94766, P0C0K6, P0C0K7, P21836, P22303, P24347, P35475, P50427, P51839, P51840, P52785, P54760, P55203, Q01634, Q02846, Q04912, Q29499, Q2KHV9, Q2T9T9, Q3UH93, Q5JZY3, Q69ZQ1, Q6NSJ0, Q6ZPS2, Q80W65, Q8BH02, Q8BYG9, Q8CG64, Q8IUL8

Diamond homologs: A1CNK4, A1D1E6, B0XNL6, B8MZ41, B9F676, D4B0X3, F4J6T7, O00906, O04893, O04931, O43451, O62653, O74254, P07768, P10253, P14410, P22861, P23739, P29064, P56526, P70699, P79403, Q09901, Q0CMA7, Q12558, Q14697, Q2M2H8, Q2UQV7, Q43763, Q4R4N7, Q4WRH9, Q5AWI5, Q5R7A9, Q653V7, Q69ZQ1, Q6NSJ0, Q6P7A9, Q8BHN3, Q92442, Q9C0Y4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	24
Uncertain significance	188
Likely benign	53
Benign	13

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2707928	NM_020702.5(MYORG):c.265dup (p.Arg89fs)	Pathogenic
2963574	NM_020702.5(MYORG):c.535_536insC (p.Gly179fs)	Pathogenic
3619439	NM_020702.5(MYORG):c.972C>G (p.Tyr324Ter)	Pathogenic
3711302	NM_020702.5(MYORG):c.1681del (p.Gln561fs)	Pathogenic
4535953	NM_020702.5(MYORG):c.346dup (p.Arg116fs)	Pathogenic
4695072	NM_020702.5(MYORG):c.325C>T (p.Gln109Ter)	Pathogenic
4729816	NM_020702.5(MYORG):c.663del (p.Phe221fs)	Pathogenic
4813692	NM_020702.5(MYORG):c.1394dup (p.Glu466fs)	Pathogenic
617689	NM_020702.5(MYORG):c.225G>A (p.Trp75Ter)	Pathogenic
617695	NM_020702.5(MYORG):c.1233del (p.Phe411fs)	Pathogenic
617697	I655T	Pathogenic
986869	NM_020702.5(MYORG):c.900C>A (p.Tyr300Ter)	Pathogenic
1013327	NM_020702.5(MYORG):c.494_509dup (p.Ala171fs)	Likely pathogenic
1176899	NM_020702.5(MYORG):c.1225G>T (p.Glu409Ter)	Likely pathogenic
1176900	NM_020702.5(MYORG):c.488G>A (p.Trp163Ter)	Likely pathogenic
1804977	NM_020702.5(MYORG):c.1788C>G (p.Tyr596Ter)	Likely pathogenic
1806199	NM_020702.5(MYORG):c.1873G>T (p.Glu625Ter)	Likely pathogenic
2573020	NM_020702.5(MYORG):c.701_702del (p.Ala234fs)	Likely pathogenic
2635176	NM_020702.5(MYORG):c.1698_1699delinsAAT (p.Asp567fs)	Likely pathogenic
2659158	NM_020702.5(MYORG):c.609del (p.Gln203fs)	Likely pathogenic
3048355	NM_020702.5(MYORG):c.1698_1699del (p.Asp567fs)	Likely pathogenic
3234546	NM_020702.5(MYORG):c.2019_2023del (p.Asp674fs)	Likely pathogenic
3597252	NM_020702.5(MYORG):c.1832G>T (p.Arg611Leu)	Likely pathogenic
3780002	NM_020702.5(MYORG):c.1889del (p.Gly630fs)	Likely pathogenic
4081525	NM_020702.5(MYORG):c.1523del (p.Gln508fs)	Likely pathogenic
4081526	NM_020702.5(MYORG):c.1270_1277dup (p.Trp426fs)	Likely pathogenic
4081527	NM_020702.5(MYORG):c.234C>A (p.Tyr78Ter)	Likely pathogenic
4085074	NM_020702.5(MYORG):c.1394del (p.Gly465fs)	Likely pathogenic
4533286	NM_020702.5(MYORG):c.1270_1277del (p.Arg424fs)	Likely pathogenic
4821708	NM_020702.5(MYORG):c.404C>A (p.Ser135Ter)	Likely pathogenic

SpliceAI

297 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34376197:C:CT	acceptor_gain	0.9900
9:34376791:AC:A	donor_gain	0.9900
9:34376792:CC:C	donor_gain	0.9900
9:34376787:GCTCA:G	donor_loss	0.9800
9:34376788:CTCAC:C	donor_loss	0.9800
9:34376789:TCA:T	donor_loss	0.9800
9:34376790:CAC:C	donor_loss	0.9800
9:34376791:A:AC	donor_gain	0.9800
9:34376792:C:CC	donor_gain	0.9800
9:34376792:C:T	donor_loss	0.9800
9:34376786:GGCTC:G	donor_loss	0.9600
9:34376801:G:C	donor_gain	0.9500
9:34373002:CTGCT:C	acceptor_gain	0.9400
9:34376791:ACC:A	donor_gain	0.9400
9:34376792:CCC:C	donor_gain	0.9400
9:34376792:CCCA:C	donor_gain	0.9400
9:34370776:CGG:C	donor_gain	0.9300
9:34376206:A:T	acceptor_gain	0.9200
9:34376835:T:TA	donor_gain	0.9200
9:34370778:G:C	donor_gain	0.9100
9:34376116:T:TA	donor_gain	0.9100
9:34376804:ACAGC:A	donor_gain	0.8900
9:34376805:CAGCC:C	donor_gain	0.8900
9:34376836:C:A	donor_gain	0.8800
9:34373007:C:CC	acceptor_gain	0.8700
9:34373004:GCT:G	acceptor_gain	0.8600
9:34373005:CTC:C	acceptor_gain	0.8600
9:34373006:TCT:T	acceptor_gain	0.8600
9:34373007:C:G	acceptor_gain	0.8600
9:34373005:CT:C	acceptor_gain	0.8400

AlphaMissense

4610 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34372092:G:C	C284W	0.999
9:34372093:C:G	C284S	0.999
9:34372093:C:T	C284Y	0.999
9:34372094:A:G	C284R	0.999
9:34372094:A:T	C284S	0.999
9:34372103:A:C	Y281D	0.999
9:34372471:C:G	C158S	0.999
9:34372471:C:T	C158Y	0.999
9:34372472:A:T	C158S	0.999
9:34370900:A:G	W682R	0.998
9:34370900:A:T	W682R	0.998
9:34371029:A:G	W639R	0.998
9:34371029:A:T	W639R	0.998
9:34372234:A:T	I237N	0.998
9:34372237:G:T	A236D	0.998
9:34372238:C:G	A236P	0.998
9:34372259:A:G	W229R	0.998
9:34372259:A:T	W229R	0.998
9:34372455:C:A	W163C	0.998
9:34372455:C:G	W163C	0.998
9:34372470:G:C	C158W	0.998
9:34372472:A:G	C158R	0.998
9:34370815:A:G	F710S	0.997
9:34370898:C:A	W682C	0.997
9:34370898:C:G	W682C	0.997
9:34370980:A:G	L655P	0.997
9:34370983:A:G	F654S	0.997
9:34371032:A:G	W638R	0.997
9:34371032:A:T	W638R	0.997
9:34371318:G:C	S542R	0.997

dbSNP variants (sampled 300 via entrez): RS1000035147 (9:34373318 C>G), RS1000107597 (9:34374785 C>T), RS1000234117 (9:34377286 G>C), RS1000457136 (9:34377032 A>C), RS1000661143 (9:34378749 G>A,C), RS1000948218 (9:34378515 G>A), RS1000985458 (9:34366385 A>C,G), RS1001314258 (9:34370578 A>C), RS1001588167 (9:34376943 G>C), RS1001752931 (9:34372368 C>A,G,T), RS1002054186 (9:34370690 G>A,C), RS1002215017 (9:34376919 C>T), RS1002664772 (9:34375697 T>C), RS1002729211 (9:34366187 A>G), RS1002960501 (9:34375305 G>A)

Disease associations

OMIM: gene MIM:618255 | disease phenotypes: MIM:618317, MIM:213600, MIM:606656

GenCC curated gene-disease

Disease	Classification	Inheritance
basal ganglia calcification, idiopathic, 7, autosomal recessive	Definitive	Autosomal recessive
bilateral striopallidodentate calcinosis	Supportive	Autosomal dominant

Mondo (3): basal ganglia calcification, idiopathic, 7, autosomal recessive (MONDO:0032673), basal ganglia calcification, idiopathic, 1 (MONDO:0024538), bilateral striopallidodentate calcinosis (MONDO:0008947)

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

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000020	Urinary incontinence
HP:0000298	Mask-like facies
HP:0000571	Hypometric saccades
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:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001268	Mental deterioration
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001310	Dysmetria
HP:0001315	Reduced tendon reflexes
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001350	Slurred speech
HP:0002015	Dysphagia
HP:0002063	Rigidity
HP:0002067	Bradykinesia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010136_34	Fruit consumption	4.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C537657	Basal ganglia calcification, idiopathic 2 (supp.)
C536275	Fahr’s disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases methylation	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	affects methylation, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	decreases reaction, affects binding	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
clothianidin	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	increases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

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