GNPTG

Summary

GNPTG (N-acetylglucosamine-1-phosphate transferase subunit gamma, HGNC:23026) is a protein-coding gene on chromosome 16p13.3, encoding N-acetylglucosamine-1-phosphotransferase subunit gamma (Q9UJJ9). Non-catalytic subunit of the N-acetylglucosamine-1-phosphotransferase complex, an enzyme that catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus.

This gene encodes the gamma sunbunit of the N-acetylglucosamine-1-phosphotransferase complex. This hexameric complex, composed of alpha, beta and gamma subunits, catalyzes the first step in synthesis of a mannose 6-phosphate lysosomal recognition marker. This enzyme complex is necessary for targeting of lysosomal hydrolases to the lysosome. Mutations in the gene encoding the gamma subunit have been associated with mucolipidosis IIIC, also known as mucolipidosis III gamma.

Source: NCBI Gene 84572 — RefSeq curated summary.

At a glance

• Gene–disease (curated): GNPTG-mucolipidosis (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 1,008 total — 78 pathogenic, 59 likely-pathogenic
• Phenotypes (HPO): 28
• MANE Select transcript: NM_032520

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23026
Approved symbol	GNPTG
Name	N-acetylglucosamine-1-phosphate transferase subunit gamma
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CAB56184, c316G12.3
Ensembl gene	ENSG00000090581
Ensembl biotype	protein_coding
OMIM	607838
Entrez	84572

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 16 protein_coding, 7 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000204679, ENST00000526820, ENST00000527076, ENST00000527137, ENST00000527168, ENST00000527876, ENST00000529110, ENST00000529957, ENST00000534197, ENST00000683366, ENST00000683887, ENST00000684100, ENST00000684126, ENST00000684688, ENST00000891784, ENST00000891785, ENST00000891786, ENST00000891787, ENST00000891788, ENST00000891789, ENST00000891790, ENST00000891791, ENST00000891792, ENST00000891793, ENST00000928980, ENST00000947151

RefSeq mRNA: 1 — MANE Select: NM_032520 NM_032520

CCDS: CCDS10436

Canonical transcript exons

ENST00000204679 — 11 exons

Exon	Start	End
ENSE00000665567	1352239	1352306
ENSE00001284338	1362997	1364113
ENSE00002189188	1351931	1352017
ENSE00003487408	1362825	1362906
ENSE00003506164	1362452	1362534
ENSE00003515102	1362206	1362320
ENSE00003516230	1362611	1362742
ENSE00003521074	1361872	1361955
ENSE00003523405	1362038	1362131
ENSE00003545614	1361743	1361797
ENSE00003720816	1352102	1352159

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.6239 / max 244.8331, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152096	46.6239	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	98.53	gold quality
right adrenal gland	UBERON:0001233	98.45	gold quality
left adrenal gland	UBERON:0001234	98.39	gold quality
left adrenal gland cortex	UBERON:0035825	98.38	gold quality
adrenal cortex	UBERON:0001235	98.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.83	gold quality
adrenal gland	UBERON:0002369	97.54	gold quality
spinal cord	UBERON:0002240	97.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.21	gold quality
anterior cingulate cortex	UBERON:0009835	96.97	gold quality
kidney epithelium	UBERON:0004819	96.95	gold quality
prefrontal cortex	UBERON:0000451	96.88	gold quality
amygdala	UBERON:0001876	96.87	gold quality
hypothalamus	UBERON:0001898	96.78	gold quality
right frontal lobe	UBERON:0002810	96.74	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.65	gold quality
cerebellar hemisphere	UBERON:0002245	96.62	gold quality
cerebellar cortex	UBERON:0002129	96.54	gold quality
putamen	UBERON:0001874	96.46	gold quality
substantia nigra	UBERON:0002038	96.40	gold quality
stromal cell of endometrium	CL:0002255	96.12	gold quality
nucleus accumbens	UBERON:0001882	96.10	gold quality
caudate nucleus	UBERON:0001873	95.97	gold quality
midbrain	UBERON:0001891	95.96	gold quality
cerebellum	UBERON:0002037	95.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.91	gold quality
adenohypophysis	UBERON:0002196	95.78	gold quality
tendon of biceps brachii	UBERON:0008188	95.75	gold quality
tibial nerve	UBERON:0001323	95.48	gold quality
pituitary gland	UBERON:0000007	95.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

15 targeting GNPTG, 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-548AT-5P	99.96	70.83	2666
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-6500-3P	97.42	67.20	867
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-4653-3P	96.26	67.03	725
HSA-MIR-632	96.08	67.17	798

Literature-anchored findings (GeneRIF, showing 24)

• The mutational spectrum of the GNPTG gene is strongly influenced by the properties of the local DNA sequence environment. (PMID:19370764)
• The study led to the identification of 11 different mutations in GNPTAB and GNPTG genes in 13 mucolipidosis II and III patients. (PMID:19659762)
• novel mutation identified in GNPTG in mucolipidosis type III gamma resulting in truncated but stable gamma-subunit;gamma subunit appears to be involved in regulation of GlcNAc-1-phosphotransferase activity rather than general binding of lysosomal enzymes (PMID:19708128)
• analysis of functional differences in alpha, beta, and gamma subunits of UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (PMID:19955174)
• results suggest that PRL-3’s roles in motility, invasion, and metastasis in colon cancer are critically controlled by the integrin beta1-ERK1/2-MMP2 signaling (PMID:20034096)
• identified mutations in GNPTG gene in subjects with stuttering (PMID:20147709)
• two novel heterozygous mutations in GNPTG, including a splice site mutation and a 1-bp deletion in a Chinese family with mucolipidosis type III gamma. (PMID:20951619)
• To date mutations in GNPTAB, GNPTG, and NAGPA have been associated with stuttering. These genes encode the lysosomal enzyme targeting pathway, defective in mucolipidosis. (Review) (PMID:22884963)
• findings expand the mutation spectrum of the GNPTG gene in Mucolipidosis type III gamma (three novel mutations were identified) (PMID:24316125)
• SNPs covering GNPTAB, GNPTG and NAGPA were subjected to genotyping, association analysis was performed on all SNPs. Significant association of rs17031962 in GNPTAB and rs882294 in NAGPA with developmental dyslexia in a Chinese population was identified after false discovery rate correction for multiple comparisons. (PMID:25643770)
• persistent stuttering is associated with mutations in GNPTG that are generally not found in mucolipidosis. (PMID:26130485)
• GlcNAc-1-phosphotransferase gamma-subunits bind to glycosylated region in the no-similarity domain 2 of alpha-subunit, which is independent on cysteine 70 identified to be responsible for alpha-subunit homodimerization. (PMID:26385638)
• we suggest that GNPTG analysis must be performed on gDNA because of the instability of mRNA containing premature stop codons and the occurrence of mRNA editing. The mRNA editing could play an important role in modulating the association between mutant genotype and clinical phenotype. (PMID:26935170)
• Analysis of the missense mutations in the gamma subunit of GlcNAc-1-phosphotransferase reported in patients with mucolipidosis III gamma shows that three of the four variants, p.G106S, p.G126S and p.C142Y, caused misfolding of the gamma subunit, while one variant, p.T286M, was normal. The misfolded gamma subunits were retained in the endoplasmic reticulum and failed to rescue the lysosomal targeting of lysosomal acid g… (PMID:27038293)
• Study identified three novel mutations in GNPTG causing Mucolipidosis type III. Some were associated with severe clinical phenotype with an earlier onset of signs and symptoms and poorer prognosis. (PMID:29170090)
• 14 variations were found in GNPTAB, GNPTG and NAGPA genes. (PMID:29289611)
• Whole exome sequencing found an insertion mutation c.478_479insTAGG in GNTPG, which cosegregated with the Mucolipidosis III Gamma disease phenotype in the family. (PMID:30235039)
• Data provide an overview on 50 mutations in GNPTG including seven novel variants. GNPTG mutations apparently are associated with a milder phenotype and better prognosis compared with GNPTAB mutations in patients with mucolipidosis. (PMID:30882951)
• We evaluated 51 stuttering individuals with a mutation in either the GNPTAB, GNPTG, NAGPA, or AP4E1 gene. Mutation carriers achieved significantly less resolution in PSI following therapy, with PSI scores showing significantly less improvement in individuals who carry a mutation (p = 0.0157, RR = 1.75, OR = 2.92) while the group difference in DWS between carriers and non-carriers was statistically not significant. (PMID:31003007)
• Disease-causing missense mutations within the N-terminal transmembrane domain of GlcNAc-1-phosphotransferase impair endoplasmic reticulum translocation or Golgi retention. (PMID:32220096)
• Identification and characterization of 30 novel pathogenic variations in 69 unrelated Indian patients with Mucolipidosis Type II and Type III. (PMID:32651481)
• Clinical, radiological and computational studies on two novel GNPTG variants causing mucolipidosis III gamma phenotypes with varying severity. (PMID:33507475)
• UDP-GlcNAc-1-Phosphotransferase Is a Clinically Important Regulator of Human and Mouse Hair Pigmentation. (PMID:34116066)
• Pathogenic variants in GNPTAB and GNPTG encoding distinct subunits of GlcNAc-1-phosphotransferase differentially impact bone resorption in patients with mucolipidosis type II and III. (PMID:34341521)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnptg	ENSDARG00000038566
mus_musculus	Gnptg	ENSMUSG00000035521

Paralogs (1): PRKCSH (ENSG00000130175)

Protein

Protein identifiers

N-acetylglucosamine-1-phosphotransferase subunit gamma — Q9UJJ9 (reviewed: Q9UJJ9)

Alternative names: GlcNAc-1-phosphotransferase subunit gamma, UDP-N-acetylglucosamine-1-phosphotransferase subunit gamma

All UniProt accessions (6): Q9UJJ9, A0A087WWA2, A0A804HI41, A0A804HIZ1, E9PQQ5, H0YEA7

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic subunit of the N-acetylglucosamine-1-phosphotransferase complex, an enzyme that catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. Binds and presents the high mannose glycans of the acceptor to the catalytic alpha and beta subunits (GNPTAB). Enhances the rate of N-acetylglucosamine-1-phosphate transfer to the oligosaccharides of acid hydrolase acceptors.

Subunit / interactions. Homodimer; disulfide-linked. Hexamer of two alpha (GNPTAB), two beta (GNPTAB) and two gamma (GNPTG) subunits; disulfide-linked. The alpha and/or the beta subunits of the enzyme constitute the catalytic subunits.

Subcellular location. Secreted. Golgi apparatus.

Tissue specificity. Widely expressed.

Post-translational modifications. Cys-245 mediates the formation of the interchain disulfide bond for formation of the homodimer. Cys-142, Cys-157 and Cys-169 are involved in intramolecular disulfide bonds formation.

Disease relevance. Mucolipidosis type III complementation group C (MLIIIC) [MIM:252605] Autosomal recessive disease of lysosomal hydrolase trafficking. Unlike the related diseases, mucolipidosis II and IIIA, the enzyme affected in mucolipidosis IIIC (GlcNAc-phosphotransferase) retains full transferase activity on synthetic substrates but lacks activity on lysosomal hydrolases. Typical clinical findings include stiffness of the hands and shoulders, claw-hand deformity, scoliosis, short stature, coarse facies, and mild intellectual disability. Radiographically, severe dysostosis multiplex of the hip is characteristic and frequently disabling. The clinical diagnosis can be confirmed by finding elevated serum lysosomal enzyme levels and/or decreased lysosomal enzyme levels in cultured fibroblasts. The disease is caused by variants affecting the gene represented in this entry. Defects in GNPTG have been suggested to play a role in susceptibility to persistent stuttering. Stuttering is a common speech disorder characterized by repetitions, prolongations, and interruptions in the flow of speech.

RefSeq proteins (1): NP_115909* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009011	Man6P_isomerase_rcpt-bd_dom_sf	Homologous_superfamily
IPR010506	DMAP1-bd	Domain
IPR012913	OS9-like_dom	Domain
IPR039794	Gtb1-like	Family
IPR044865	MRH_dom	Domain

Pfam: PF07915

Enzyme classification (BRENDA):

• EC 2.7.8.17 — UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase (BRENDA: 11 organisms, 41 substrates, 24 inhibitors, 33 Km, 18 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
METHYL-ALPHA-D-MANNOSIDE	0.021–183	5
UDP-GLCNAC	0.021–0.2	5
UTEROFERRIN	0.022–0.065	4
CATHEPSIN D	0.018–0.025	3
DNASE I	0.03–0.06	2
MAN9GLCNAC1 OLIGOSACCHARIDE	3.3–5.7	2
METHYL ALPHA-D-MANNOPYRANOSIDE	33–48	2
NPC2	0.352–0.367	2
PRO-TRIPEPTIDYL PEPTIDASE	0.11	2
RIBONUCLEASE B	0.916–1.244	2
RNASE B	0.5–0.556	2
SOYBEAN AGGLUTININ	1	2

UniProt features (21 total): sequence variant 8, disulfide bond 4, domain 2, glycosylation site 2, signal peptide 1, chain 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJJ9-F1	80.63	0.61

Functional residue map

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

Disulfide bonds (4): 142–169, 245, 71–84, 129–157

Glycosylation sites (2): 88, 115

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GOBP_N_GLYCAN_PROCESSING, GOBP_LYSOSOMAL_TRANSPORT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_PROTEIN_TARGETING, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME, GOBP_CARBOHYDRATE_PHOSPHORYLATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_PROTEIN_LOCALIZATION_TO_LYSOSOME, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS

GO Biological Process (2): N-glycan processing to lysosome (GO:0016256), carbohydrate phosphorylation (GO:0046835)

GO Molecular Function (2): protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (4): Golgi apparatus (GO:0005794), extracellular exosome (GO:0070062), UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase complex (GO:0070622), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
N-glycan processing	1
protein targeting to lysosome	1
carbohydrate metabolic process	1
phosphorylation	1
identical protein binding	1
protein dimerization activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
lysosome	1
transferase complex, transferring phosphorus-containing groups	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1088 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNPTG	GNPTAB	Q3T906	996
GNPTG	NAGPA	Q9UK23	983
GNPTG	FUCA2	Q9BTY2	659
GNPTG	CTSD	P07339	640
GNPTG	AP4E1	Q9UPM8	626
GNPTG	DMAP1	Q9NPF5	569
GNPTG	ATP2C2	O75185	498
GNPTG	MAN2B1	O00754	488
GNPTG	CMIP	Q8IY22	482
GNPTG	MBTPS1	Q14703	480
GNPTG	IGF2R	P11717	472
GNPTG	DPAGT1	Q9H3H5	465
GNPTG	NAGLU	P54802	447
GNPTG	HGSNAT	Q68CP4	444
GNPTG	UGGT1	Q9NYU2	440

IntAct

65 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
GNPTG	GNPTAB	psi-mi:“MI:0914”(association)	0.620
GNPTAB	GNPTG	psi-mi:“MI:0915”(physical association)	0.620
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
SRPK1	GNPTG	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GNPTG	GNPTAB	psi-mi:“MI:0915”(physical association)	0.400
Cdc16	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Cdc23	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Cdc26		psi-mi:“MI:0914”(association)	0.350
Cdc26	PEX10	psi-mi:“MI:0914”(association)	0.350
Anapc2	ANAPC15	psi-mi:“MI:0914”(association)	0.350
ANAPC15		psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
NTAQ1	SBNO1	psi-mi:“MI:0914”(association)	0.350
ZPLD1	CEACAM8	psi-mi:“MI:0914”(association)	0.350
GNPTAB	GNPTAB	psi-mi:“MI:0914”(association)	0.350
rep	B4GALT3	psi-mi:“MI:0914”(association)	0.350
C22orf42	CYB5R3	psi-mi:“MI:0914”(association)	0.350
CATSPERE	PYGB	psi-mi:“MI:0914”(association)	0.350
C5AR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), GNPTG (Affinity Capture-MS), SPSB3 (Affinity Capture-MS), GNPTG (Affinity Capture-MS)

ESM2 similar proteins: A1Z623, A2SXS5, A8YXY3, F1LQY6, O02718, O19011, O60613, P01137, P04202, P07200, P09533, P11456, P18341, P50747, P54831, Q08BI9, Q0P5I0, Q1LZ96, Q2KIJ6, Q2TBX5, Q38HS2, Q3UHE1, Q3UX43, Q58CS8, Q5C9Z4, Q5R812, Q5RB75, Q6IEE6, Q6PCX7, Q6X4M2, Q802F3, Q802G7, Q8BJQ9, Q8IVD9, Q8NC56, Q8R1N4, Q8R1T1, Q8TDX6, Q8VHC3, Q8WUX9

Diamond homologs: A2WNF5, Q04924, Q58CS8, Q5NBP9, Q6S5C2, Q9FM96, Q9UJJ9, Q9USH8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1008 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	78
Likely pathogenic	59
Uncertain significance	288
Likely benign	506
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071119	NM_032520.5(GNPTG):c.366G>A (p.Trp122Ter)	Pathogenic
1072159	NM_032520.5(GNPTG):c.665dup (p.Glu223fs)	Pathogenic
1073680	NM_032520.5(GNPTG):c.514del (p.His172fs)	Pathogenic
1074640	NM_032520.5(GNPTG):c.717del (p.Phe239fs)	Pathogenic
1075131	NM_032520.5(GNPTG):c.89_90del (p.Val30fs)	Pathogenic
1076841	NM_032520.5(GNPTG):c.417_429del (p.Leu140fs)	Pathogenic
1354910	NM_032520.5(GNPTG):c.203C>A (p.Ser68Ter)	Pathogenic
1357296	NM_032520.5(GNPTG):c.601_602dup (p.Gln203fs)	Pathogenic
1367203	NM_032520.5(GNPTG):c.133C>T (p.Gln45Ter)	Pathogenic
1367242	NM_032520.5(GNPTG):c.294G>A (p.Trp98Ter)	Pathogenic
1389901	NM_032520.5(GNPTG):c.685C>T (p.Gln229Ter)	Pathogenic
1425155	NM_032520.5(GNPTG):c.571del (p.Gln190_Val191insTer)	Pathogenic
1429702	NM_032520.5(GNPTG):c.609+1G>T	Pathogenic
1429968	NM_032520.5(GNPTG):c.183dup (p.Val62fs)	Pathogenic
1450957	NM_032520.5(GNPTG):c.607C>T (p.Gln203Ter)	Pathogenic
1451351	NM_032520.5(GNPTG):c.659dup (p.Thr221fs)	Pathogenic
1455613	NM_032520.5(GNPTG):c.234-1G>C	Pathogenic
1460071	NM_032520.5(GNPTG):c.385_400del (p.Cys129fs)	Pathogenic
1526169	NM_032520.5(GNPTG):c.638_639del (p.Leu212_Phe213insTer)	Pathogenic
1685858	NM_032520.5(GNPTG):c.735C>A (p.Cys245Ter)	Pathogenic
2118763	NM_032520.5(GNPTG):c.300del (p.Tyr101fs)	Pathogenic
2123702	NM_032520.5(GNPTG):c.564G>A (p.Trp188Ter)	Pathogenic
2137750	NM_032520.5(GNPTG):c.654_657del (p.Gly217_Tyr218insTer)	Pathogenic
21713	NM_032520.5(GNPTG):c.196C>T (p.Arg66Ter)	Pathogenic
21714	NM_032520.5(GNPTG):c.318-1G>C	Pathogenic
21719	NM_032520.5(GNPTG):c.609+28_610-16del	Pathogenic
21720	NM_032520.5(GNPTG):c.610-1G>T	Pathogenic
21723	NM_032520.5(GNPTG):c.639del (p.Phe213fs)	Pathogenic
2181376	NM_032520.5(GNPTG):c.102del (p.Asn34fs)	Pathogenic
2444155	NM_032520.5(GNPTG):c.610-1G>A	Pathogenic

SpliceAI

1481 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1361867:CCCA:C	acceptor_loss	1.0000
16:1361868:CCAG:C	acceptor_loss	1.0000
16:1361870:A:AG	acceptor_gain	1.0000
16:1361870:AG:A	acceptor_gain	1.0000
16:1361871:G:GA	acceptor_gain	1.0000
16:1361871:GG:G	acceptor_gain	1.0000
16:1361871:GGT:G	acceptor_gain	1.0000
16:1361953:CGGG:C	donor_loss	1.0000
16:1361954:GG:G	donor_gain	1.0000
16:1361955:GG:G	donor_gain	1.0000
16:1361955:GGTG:G	donor_loss	1.0000
16:1361956:G:GG	donor_gain	1.0000
16:1361956:GT:G	donor_loss	1.0000
16:1361957:T:A	donor_loss	1.0000
16:1361958:GA:G	donor_loss	1.0000
16:1362032:CCCCA:C	acceptor_loss	1.0000
16:1362033:CCCAG:C	acceptor_loss	1.0000
16:1362034:CCA:C	acceptor_loss	1.0000
16:1362035:CA:C	acceptor_loss	1.0000
16:1362036:A:AC	acceptor_loss	1.0000
16:1362036:A:AG	acceptor_gain	1.0000
16:1362037:G:GG	acceptor_gain	1.0000
16:1362037:GC:G	acceptor_gain	1.0000
16:1362037:GCATC:G	acceptor_gain	1.0000
16:1362200:CCCCA:C	acceptor_loss	1.0000
16:1362201:CCCA:C	acceptor_loss	1.0000
16:1362316:GCTAG:G	donor_gain	1.0000
16:1362317:C:G	donor_gain	1.0000
16:1362317:CTAG:C	donor_loss	1.0000
16:1362319:AGG:A	donor_loss	1.0000

AlphaMissense

1980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1361932:G:C	W98C	0.998
16:1361932:G:T	W98C	0.998
16:1362051:T:A	W111R	0.998
16:1362051:T:C	W111R	0.998
16:1362053:G:C	W111C	0.998
16:1362053:G:T	W111C	0.998
16:1361911:G:C	Q91H	0.997
16:1361911:G:T	Q91H	0.997
16:1361913:A:C	H92P	0.995
16:1361930:T:A	W98R	0.995
16:1361930:T:C	W98R	0.995
16:1361954:G:C	G106R	0.995
16:1362042:T:A	W108R	0.995
16:1362042:T:C	W108R	0.995
16:1362044:G:C	W108C	0.995
16:1362044:G:T	W108C	0.995
16:1362263:T:C	C157R	0.995
16:1362264:G:A	C157Y	0.995
16:1361880:A:G	Y81C	0.994
16:1361888:T:A	C84S	0.994
16:1361889:G:C	C84S	0.994
16:1362263:T:A	C157S	0.994
16:1362264:G:C	C157S	0.994
16:1361916:A:T	E93V	0.993
16:1361955:G:A	G106D	0.993
16:1361955:G:T	G106V	0.993
16:1362096:G:T	G126C	0.993
16:1362097:G:A	G126D	0.993
16:1362097:G:T	G126V	0.993
16:1362105:T:A	C129S	0.993

dbSNP variants (sampled 300 via entrez): RS1000238481 (16:1364473 G>A), RS1000273462 (16:1362262 C>T), RS1000545836 (16:1355613 T>C), RS1000579651 (16:1354781 C>A,T), RS1000804553 (16:1358844 T>C), RS1000826301 (16:1350444 T>A), RS1000917997 (16:1358302 G>A), RS1000935039 (16:1351074 A>C), RS1001208113 (16:1357245 C>T), RS1001218165 (16:1352691 G>A), RS1001290329 (16:1361622 T>C,G), RS1001470479 (16:1360616 T>A), RS1001607169 (16:1352982 T>TC), RS1001709426 (16:1350866 T>C,G), RS1001955796 (16:1362764 G>A)

Disease associations

OMIM: gene MIM:607838 | disease phenotypes: MIM:252605

GenCC curated gene-disease

Disease	Classification	Inheritance
GNPTG-mucolipidosis	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
GNPTG-mucolipidosis	Definitive	AR

Mondo (3): GNPTG-mucolipidosis (MONDO:0009652), inherited retinal dystrophy (MONDO:0019118), mucolipidosis (MONDO:0019248)

Orphanet (4): Mucolipidosis type III gamma (Orphanet:423470), Mucolipidosis type III (Orphanet:577), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Mucolipidosis (Orphanet:79212)

HPO phenotypes

28 total (29 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000280	Coarse facial features
HP:0000470	Short neck
HP:0000545	Myopia
HP:0000768	Pectus carinatum
HP:0000943	Dysostosis multiplex
HP:0001249	Intellectual disability
HP:0001256	Mild intellectual disability
HP:0001387	Joint stiffness
HP:0001650	Aortic valve stenosis
HP:0001659	Aortic regurgitation
HP:0001763	Pes planus
HP:0002650	Scoliosis
HP:0002808	Kyphosis
HP:0002829	Arthralgia
HP:0002857	Genu valgum
HP:0002869	Flared iliac wing
HP:0003307	Hyperlordosis
HP:0003333	Increased serum beta-hexosaminidase
HP:0003370	Flat capital femoral epiphysis
HP:0003538	Increased iduronate sulfatase level
HP:0003621	Juvenile onset
HP:0004322	Short stature
HP:0007759	Opacification of the corneal stroma
HP:0008155	Mucopolysacchariduria
HP:0034337	Claw hand deformity
HP:0034665	Shoulder contracture
HP:0034681	Finger joint contracture
HP:0000556	Retinal dystrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_258	Blood protein levels	8.000000e-14

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009081	Mucolipidoses	C05.116.198.371; C10.228.140.163.100.435.590; C16.320.565.189.435.590; C16.320.565.202.670; C16.320.565.595.554.590; C18.452.132.100.435.590; C18.452.648.189.435.590; C18.452.648.202.670; C18.452.648.595.554.590
D058499	Retinal Dystrophies	C11.768.585.658
C565367	Mucolipidosis III Gamma (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bufotalin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Lead	affects expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tunicamycin	increases expression	1
Valproic Acid	increases expression, increases methylation	1
Zinc	increases expression	1
Cyclosporine	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

8 cell lines: 6 cancer cell line, 2 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D5FH	HeLa::TMEM192-3xHA GNPTG partial KO	Cancer cell line	Female
CVCL_IN49	GM03391	Finite cell line	Male
CVCL_IN50	GM03392	Finite cell line	Female
CVCL_SQ20	HAP1 GNPTG (-) 1	Cancer cell line	Male
CVCL_SQ21	HAP1 GNPTG (-) 2	Cancer cell line	Male
CVCL_SQ22	HAP1 GNPTG (-) 3	Cancer cell line	Male
CVCL_SQ23	HAP1 GNPTG (-) 4	Cancer cell line	Male
CVCL_SQ24	HAP1 GNPTG (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality