POMGNT2

Summary

POMGNT2 (protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-), HGNC:25902) is a protein-coding gene on chromosome 3p22.1, encoding Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 (Q8NAT1). O-linked mannose beta-1,4-N-acetylglucosaminyltransferase that transfers UDP-N-acetyl-D-glucosamine to the 4-position of the mannose to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosylprotein.

This gene encodes a protein with glycosyltransferase activity although its function is not currently known.

Source: NCBI Gene 84892 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy caused by variation in POMGNT2 (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 496 total — 21 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 62
• MANE Select transcript: NM_032806

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25902
Approved symbol	POMGNT2
Name	protein O-linked mannose N-acetylglucosaminyltransferase 2 (beta 1,4-)
Location	3p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14566, AGO61
Ensembl gene	ENSG00000144647
Ensembl biotype	protein_coding
OMIM	614828
Entrez	84892

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000344697, ENST00000441964, ENST00000686643, ENST00000687440, ENST00000689987, ENST00000690520, ENST00000692017, ENST00000693717, ENST00000909987, ENST00000909988, ENST00000911269, ENST00000953069

RefSeq mRNA: 1 — MANE Select: NM_032806 NM_032806

CCDS: CCDS2709

Canonical transcript exons

ENST00000344697 — 2 exons

Exon	Start	End
ENSE00003992957	43079234	43081536
ENSE00003992969	43105836	43106079

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 93.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8739 / max 73.0206, expressed in 1705 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41835	5.4016	1636
41834	2.4723	1222

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	93.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.48	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.37	silver quality
left uterine tube	UBERON:0001303	92.34	gold quality
cerebellar hemisphere	UBERON:0002245	92.25	gold quality
cerebellar cortex	UBERON:0002129	92.22	gold quality
left ventricle myocardium	UBERON:0006566	92.11	silver quality
cerebellum	UBERON:0002037	92.08	gold quality
body of uterus	UBERON:0009853	91.73	gold quality
cerebellar vermis	UBERON:0004720	91.12	gold quality
prefrontal cortex	UBERON:0000451	90.98	gold quality
right frontal lobe	UBERON:0002810	90.34	gold quality
substantia nigra pars compacta	UBERON:0001965	89.79	gold quality
frontal cortex	UBERON:0001870	89.64	gold quality
right ovary	UBERON:0002118	89.55	gold quality
neocortex	UBERON:0001950	89.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.95	gold quality
myometrium	UBERON:0001296	88.87	gold quality
anterior cingulate cortex	UBERON:0009835	88.74	gold quality
gastrocnemius	UBERON:0001388	88.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.54	gold quality
nucleus accumbens	UBERON:0001882	88.37	gold quality
left ovary	UBERON:0002119	88.12	gold quality
apex of heart	UBERON:0002098	88.07	gold quality
cerebral cortex	UBERON:0000956	87.89	gold quality
adult organism	UBERON:0007023	87.87	gold quality
caudate nucleus	UBERON:0001873	87.81	gold quality
putamen	UBERON:0001874	87.67	gold quality
muscle of leg	UBERON:0001383	87.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAP2A

miRNA regulators (miRDB)

31 targeting POMGNT2, 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-5193	100.00	67.26	1744
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-6871-5P	98.90	66.67	671
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-15B-3P	97.85	66.68	974
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-194-3P	97.36	65.96	1027

Literature-anchored findings (GeneRIF, showing 4)

• Using WES in consanguineous WWS-affected families, we found multiple deleterious mutations in GTDC2 (also known as AGO61). . (PMID:22958903)
• GTDC2 generates CTD110.6 antibody-reactive N-acetylglucosamine epitopes on the O-mannosylated alpha-dystroglycan. (PMID:24041696)
• POMGNT2 when two of the conserved amino acids are replaced. These findings begin to define the selectivity of POMGNT2 and suggest that this enzyme functions as a gatekeeper enzyme to prevent the vast majority of O-mannosylated sites on proteins from becoming modified with glycan structures functional for binding laminin globular domain-containing proteins (PMID:27932460)
• The structure of POMGNT2 provides new insights into the mechanism to determine the functional O-mannosylation site on alpha-dystroglycan. (PMID:33893702)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pomgnt2	ENSDARG00000010941
mus_musculus	Pomgnt2	ENSMUSG00000066235
rattus_norvegicus	Pomgnt2	ENSRNOG00000019492

Paralogs (1): EOGT (ENSG00000163378)

Protein

Protein identifiers

Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 — Q8NAT1 (reviewed: Q8NAT1)

Alternative names: Extracellular O-linked N-acetylglucosamine transferase-like, Glycosyltransferase-like domain-containing protein 2

All UniProt accessions (1): Q8NAT1

UniProt curated annotations — full annotation on UniProt →

Function. O-linked mannose beta-1,4-N-acetylglucosaminyltransferase that transfers UDP-N-acetyl-D-glucosamine to the 4-position of the mannose to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosylprotein. Involved in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in the brain, muscle, heart, and kidney in both fetus and adult. In the brain, highest expression in the cortex and cerebellum. Highly expressed in the pancreas.

Disease relevance. Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A8 (MDDGA8) [MIM:614830] An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound intellectual disability, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy-dystroglycanopathy limb-girdle C8 (MDDGC8) [MIM:618135] An autosomal recessive muscular disease with onset in childhood, characterized by limb-girdle muscular dystrophy and intellectual disability without brain malformation. Disease severity is highly variable and some patients may be clinically asymptomatic. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 61 family.

RefSeq proteins (1): NP_116195* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR007657	Glycosyltransferase_61	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR049625	Glyco_transf_61_cat	Domain

Pfam: PF04577

Enzyme classification (BRENDA):

• EC 2.4.1.312 — protein O-mannose beta-1,4-N-acetylglucosaminyltransferase (BRENDA: 1 organisms, 10 substrates, 0 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3-O-(ALPHA-D-MANNOSYL)-L-THREONYL-[PKRVRRQIHA-T-	1.2–2.2	2
3-O-(ALPHA-D-MANNOSYL)-L-THREONYL-[TIRTRGAIIQ-T-	0.8–2.6	2
3-O-(ALPHA-D-MANNOSYL)-L-THREONYL-[IQEPPSRIVP-T-	0.1	1
3-O-(ALPHA-D-MANNOSYL)-L-THREONYL-[YVEP-T-AV]	11	1

Catalyzed reactions (Rhea), 1 shown:

• 3-O-(alpha-D-mannosyl)-L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl)-L-threonyl-[protein] + UDP + H(+) (RHEA:37663)

UniProt features (64 total): strand 25, helix 20, turn 7, sequence variant 5, topological domain 2, glycosylation site 2, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6XFI	X-RAY DIFFRACTION	2
6XI2	X-RAY DIFFRACTION	2.57
8KB7	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NAT1-F1	92.62	0.84

Functional residue map

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

Glycosylation sites (2): 99, 276

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8932505	DAG1 core M3 glycosylations

MSigDB gene sets: 185 (showing top): GOBP_NEUROGENESIS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, chr3p22, GOBP_NEURON_MIGRATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_HEXOSYLTRANSFERASE_ACTIVITY, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY, GOMF_UDP_GLYCOSYLTRANSFERASE_ACTIVITY, GOMF_ACETYLGLUCOSAMINYLTRANSFERASE_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN

GO Biological Process (4): neuron migration (GO:0001764), protein O-linked glycosylation (GO:0006493), protein O-linked glycosylation via mannose (GO:0035269), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (5): acetylglucosaminyltransferase activity (GO:0008375), protein O-acetylglucosaminyltransferase activity (GO:0097363), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DAG1 glycosylations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	1
generation of neurons	1
glycoprotein biosynthetic process	1
protein O-linked glycosylation	1
UDP-glycosyltransferase activity	1
hexosyltransferase activity	1
acetylglucosaminyltransferase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
transferase activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POMGNT2	B3GALNT2	Q8NCR0	899
POMGNT2	RXYLT1	Q9Y2B1	893
POMGNT2	POMK	Q9H5K3	892
POMGNT2	POMT1	Q9Y6A1	874
POMGNT2	POMT2	Q9UKY4	873
POMGNT2	POMGNT1	Q8WZA1	864
POMGNT2	FKRP	Q9H9S5	862
POMGNT2	FKTN	O75072	860
POMGNT2	B4GAT1	O43505	845
POMGNT2	GMPPB	Q9Y5P6	819
POMGNT2	DPM2	O94777	786
POMGNT2	DOLK	Q9UPQ8	774
POMGNT2	DPM1	O60762	764
POMGNT2	DPM3	Q9P2X0	757
POMGNT2	CRPPA	A4D126	745

IntAct

106 interactions, top by confidence:

A	B	Type	Score
UBA5	GABARAPL2	psi-mi:“MI:0914”(association)	0.950
ELMO1	DOCK1	psi-mi:“MI:0914”(association)	0.940
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
POMGNT2	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
PLAUR	PLAU	psi-mi:“MI:0914”(association)	0.560
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
POMGNT2	PECR	psi-mi:“MI:0914”(association)	0.530
PON2	NPC1	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
SLC9A6	IFNGR1	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
POMGNT2	NPDC1	psi-mi:“MI:0915”(physical association)	0.400
FOXL2	RTCA	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
POMGNT2	EIF4E2	psi-mi:“MI:0914”(association)	0.350

BioGRID (102): NOTCH2NL (Two-hybrid), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), PECR (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS)

ESM2 similar proteins: A2BGL3, D4PHA7, F4I6V0, O43916, O88199, Q0IIY2, Q13219, Q16WU7, Q28CF8, Q2TBF2, Q505J3, Q5DTK1, Q5E9N5, Q5NDE3, Q5NDE4, Q5NDE5, Q5NDE6, Q5NDE7, Q5NDE8, Q5NDF0, Q5NDF1, Q5RJQ0, Q5XHM7, Q64610, Q658N2, Q66PG1, Q66PG2, Q66PG3, Q68CR1, Q6DBY9, Q6L8S8, Q70JA7, Q7LFX5, Q7LGC8, Q80TS8, Q80XH4, Q811B1, Q8BW41, Q8C1F4, Q8CHI9

Diamond homologs: Q5NDE3, Q5NDE4, Q5NDE5, Q5NDE6, Q5NDE7, Q5NDE8, Q5NDE9, Q5NDF0, Q5NDF1, Q5NDF2, Q8BW41, Q8NAT1, A0JND3, Q9VQB7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 135 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.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	10	14.8×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	6
Uncertain significance	266
Likely benign	166
Benign	9

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1055376	NM_032806.6(POMGNT2):c.1326G>A (p.Trp442Ter)	Pathogenic
1252076	NM_032806.6(POMGNT2):c.503T>C (p.Phe168Ser)	Pathogenic
1376803	NM_032806.6(POMGNT2):c.509del (p.Asp170fs)	Pathogenic
1400524	NM_032806.6(POMGNT2):c.118C>T (p.Arg40Ter)	Pathogenic
1452812	NM_032806.6(POMGNT2):c.820_821del (p.Lys274fs)	Pathogenic
1453141	NM_032806.6(POMGNT2):c.410_411delinsG (p.Ala137fs)	Pathogenic
1459409	NC_000003.11:g.(?43121181)(43122923_?)del	Pathogenic
1997096	NM_032806.6(POMGNT2):c.40del (p.Val14fs)	Pathogenic
2055124	NM_032806.6(POMGNT2):c.1510del (p.Val504fs)	Pathogenic
2058172	NM_032806.6(POMGNT2):c.381_382del (p.Gln128fs)	Pathogenic
2142831	NM_032806.6(POMGNT2):c.817_818del (p.Glu273fs)	Pathogenic
3620611	NM_032806.6(POMGNT2):c.248G>A (p.Trp83Ter)	Pathogenic
37207	NM_032806.6(POMGNT2):c.1333C>T (p.Arg445Ter)	Pathogenic
436373	NM_032806.6(POMGNT2):c.745C>T (p.Gln249Ter)	Pathogenic
4739533	NM_032806.6(POMGNT2):c.851del (p.Leu284fs)	Pathogenic
4812128	NM_032806.6(POMGNT2):c.740_741del (p.Phe247fs)	Pathogenic
545449	NM_032806.6(POMGNT2):c.758C>T (p.Pro253Leu)	Pathogenic
565308	NM_032806.6(POMGNT2):c.494T>C (p.Met165Thr)	Pathogenic
660661	NM_032806.6(POMGNT2):c.1042C>T (p.Gln348Ter)	Pathogenic
694624	NM_032806.6(POMGNT2):c.590G>A (p.Trp197Ter)	Pathogenic
859488	NM_032806.6(POMGNT2):c.1000_1003del (p.Leu334fs)	Pathogenic
1058894	NM_032806.6(POMGNT2):c.1555G>T (p.Glu519Ter)	Likely pathogenic
1708866	NM_032806.6(POMGNT2):c.1234G>A (p.Gly412Arg)	Likely pathogenic
2226761	NM_032806.6(POMGNT2):c.880C>T (p.Arg294Ter)	Likely pathogenic
3008348	NM_032806.6(POMGNT2):c.1170T>G (p.Tyr390Ter)	Likely pathogenic
3780481	NM_032806.6(POMGNT2):c.1264C>T (p.Gln422Ter)	Likely pathogenic
419374	NM_032806.6(POMGNT2):c.1216G>T (p.Glu406Ter)	Likely pathogenic

SpliceAI

392 predictions. Top by Δscore:

Variant	Effect	Δscore
3:43105830:TCTTA:T	donor_loss	1.0000
3:43105831:CTTA:C	donor_loss	1.0000
3:43105832:TTAC:T	donor_loss	1.0000
3:43105833:TACCT:T	donor_loss	1.0000
3:43081535:GC:G	acceptor_gain	0.9900
3:43081536:CC:C	acceptor_gain	0.9900
3:43081537:CTGCA:C	acceptor_loss	0.9900
3:43082553:C:CA	donor_gain	0.9900
3:43105834:A:AC	donor_gain	0.9900
3:43105835:C:CC	donor_gain	0.9900
3:43081533:AAGC:A	acceptor_gain	0.9800
3:43081534:AGC:A	acceptor_gain	0.9800
3:43081537:C:CC	acceptor_gain	0.9800
3:43081532:AAAGC:A	acceptor_gain	0.9600
3:43097402:CAGAT:C	donor_gain	0.9600
3:43081541:A:T	acceptor_gain	0.9400
3:43082629:AT:A	donor_gain	0.9300
3:43081540:C:CT	acceptor_gain	0.9200
3:43082585:G:A	donor_gain	0.9000
3:43082630:T:TA	donor_gain	0.8900
3:43082554:C:A	donor_gain	0.8700
3:43105656:CACG:C	donor_gain	0.8700
3:43105640:C:CA	donor_gain	0.8600
3:43082550:ACTC:A	donor_gain	0.8500
3:43082551:CTCC:C	donor_gain	0.8500
3:43082664:TGA:T	donor_gain	0.8500
3:43105658:CG:C	donor_gain	0.8500
3:43105683:T:A	donor_gain	0.8500
3:43097397:T:TA	donor_gain	0.8400
3:43082681:TG:T	donor_gain	0.8000

AlphaMissense

3766 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:43079750:C:G	R561P	0.999
3:43079916:A:G	W506R	0.999
3:43079916:A:T	W506R	0.999
3:43081195:G:C	C79W	0.999
3:43081197:A:G	C79R	0.999
3:43081227:A:G	C69R	0.999
3:43079899:G:C	N511K	0.998
3:43079899:G:T	N511K	0.998
3:43080403:G:C	S343R	0.998
3:43080403:G:T	S343R	0.998
3:43080405:T:G	S343R	0.998
3:43080708:A:G	W242R	0.998
3:43080708:A:T	W242R	0.998
3:43080748:G:C	C228W	0.998
3:43080917:A:G	L172P	0.998
3:43080923:T:A	D170V	0.998
3:43081177:G:C	C85W	0.998
3:43081179:A:G	C85R	0.998
3:43081196:C:G	C79S	0.998
3:43081196:C:T	C79Y	0.998
3:43081197:A:T	C79S	0.998
3:43081202:C:G	R77P	0.998
3:43081225:G:C	C69W	0.998
3:43081226:C:G	C69S	0.998
3:43081226:C:T	C69Y	0.998
3:43081227:A:T	C69S	0.998
3:43079746:G:C	C562W	0.997
3:43079748:A:G	C562R	0.997
3:43079906:G:T	P509Q	0.997
3:43079914:C:A	W506C	0.997

dbSNP variants (sampled 300 via entrez): RS1000042010 (3:43089123 G>A,C), RS1000081100 (3:43088069 A>G), RS1000095344 (3:43088846 G>A), RS1000161720 (3:43089438 G>C), RS1000165809 (3:43108009 G>A,C), RS1000262883 (3:43095868 G>A), RS1000305675 (3:43087668 G>A), RS1000365760 (3:43101827 G>A), RS1000700661 (3:43100465 C>T), RS1000906471 (3:43106421 G>T), RS1000947133 (3:43083682 T>C), RS1001229100 (3:43088430 G>A,T), RS1001285393 (3:43080698 T>C), RS1001295649 (3:43084054 C>G,T), RS1001434125 (3:43095405 C>T)

Disease associations

OMIM: gene MIM:614828 | disease phenotypes: MIM:614830, MIM:618135

GenCC curated gene-disease

Disease	Classification	Inheritance
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8	Definitive	Autosomal recessive
myopathy caused by variation in POMGNT2	Strong	Autosomal recessive
muscular dystrophy-dystroglycanopathy, type A	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
myopathy caused by variation in POMGNT2	Definitive	AR

Mondo (4): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (MONDO:0013904), muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8 (MONDO:0029135), muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171), myopathy caused by variation in POMGNT2 (MONDO:0700069)

Orphanet (1): Walker-Warburg syndrome (Orphanet:899)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000528	Anophthalmia
HP:0000541	Retinal detachment
HP:0000556	Retinal dystrophy
HP:0000568	Microphthalmia
HP:0000587	Abnormal optic nerve morphology
HP:0000612	Iris coloboma
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001274	Agenesis of corpus callosum
HP:0001284	Areflexia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000862_5	Bipolar disorder and schizophrenia	8.000000e-07
GCST006585_2821	Blood protein levels	4.000000e-30
GCST009356_3	Nonsyndromic cleft palate	2.000000e-10

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058494	Walker-Warburg Syndrome	C10.500.507.450.499.249.500; C11.270.881; C16.131.666.507.450.499.249.500; C16.320.577.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
bisphenol A	decreases methylation, affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
manganese chloride	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	increases expression, affects cotreatment	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	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Coal	increases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Triclosan	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TF16	HAP1 POMGNT2 (-) 1	Cancer cell line	Male
CVCL_TF17	HAP1 POMGNT2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry