POMT2

Summary

POMT2 (protein O-mannosyltransferase 2, HGNC:19743) is a protein-coding gene on chromosome 14q24.3, encoding Protein O-mannosyl-transferase 2 (Q9UKY4). Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.

The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT1 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS).

Source: NCBI Gene 29954 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy caused by variation in POMT2 (Definitive, ClinGen) — +7 more curated relationships
• Clinical variants (ClinVar): 1,307 total — 71 pathogenic, 63 likely-pathogenic
• Phenotypes (HPO): 181
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_013382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19743
Approved symbol	POMT2
Name	protein O-mannosyltransferase 2
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	LGMD2N
Ensembl gene	ENSG00000009830
Ensembl biotype	protein_coding
OMIM	607439
Entrez	29954

Gene structure

Transcript identifiers

Ensembl transcripts: 77 — 24 protein_coding_CDS_not_defined, 23 nonsense_mediated_decay, 17 protein_coding, 12 retained_intron, 1 non_stop_decay

ENST00000261534, ENST00000452340, ENST00000553863, ENST00000553880, ENST00000554564, ENST00000554767, ENST00000554884, ENST00000554948, ENST00000555134, ENST00000555675, ENST00000555710, ENST00000555788, ENST00000556171, ENST00000556326, ENST00000556394, ENST00000556404, ENST00000556446, ENST00000556851, ENST00000556880, ENST00000557289, ENST00000557525, ENST00000557675, ENST00000602717, ENST00000682128, ENST00000682247, ENST00000682377, ENST00000682382, ENST00000682395, ENST00000682459, ENST00000682467, ENST00000682560, ENST00000682615, ENST00000682706, ENST00000682729, ENST00000682795, ENST00000682891, ENST00000682895, ENST00000682897, ENST00000682925, ENST00000682955, ENST00000682973, ENST00000683095, ENST00000683167, ENST00000683188, ENST00000683285, ENST00000683300, ENST00000683328, ENST00000683380, ENST00000683398, ENST00000683551, ENST00000683585, ENST00000683721, ENST00000683784, ENST00000683801, ENST00000683828, ENST00000683907, ENST00000684009, ENST00000684066, ENST00000684102, ENST00000684172, ENST00000684259, ENST00000684344, ENST00000684444, ENST00000684479, ENST00000684528, ENST00000684534, ENST00000684538, ENST00000684549, ENST00000684554, ENST00000684600, ENST00000684670, ENST00000684746, ENST00000905355, ENST00000923942, ENST00000947742, ENST00000947743, ENST00000947744

RefSeq mRNA: 1 — MANE Select: NM_013382 NM_013382

CCDS: CCDS9857

Canonical transcript exons

ENST00000261534 — 21 exons

Exon	Start	End
ENSE00001238373	77274956	77277481
ENSE00001238379	77320434	77320883
ENSE00003472234	77278394	77278508
ENSE00003473207	77284950	77285041
ENSE00003503606	77286744	77286822
ENSE00003519224	77311949	77312033
ENSE00003520034	77278729	77278869
ENSE00003548175	77283797	77283873
ENSE00003554941	77304692	77304800
ENSE00003564968	77299455	77299561
ENSE00003591730	77280392	77280463
ENSE00003593636	77296164	77296273
ENSE00003606054	77280021	77280080
ENSE00003627906	77285481	77285632
ENSE00003628022	77291314	77291380
ENSE00003630025	77302835	77302943
ENSE00003644918	77288762	77288831
ENSE00003658927	77306337	77306441
ENSE00003674459	77279823	77279928
ENSE00003675519	77298689	77298771
ENSE00003686871	77301090	77301249

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 97.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3031 / max 59.2934, expressed in 1740 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144223	8.1156	1728
144222	0.3833	183
144221	0.3363	141
207310	0.2254	116
144220	0.1647	60
144219	0.0695	46
144218	0.0083	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	97.75	gold quality
left testis	UBERON:0004533	97.71	gold quality
testis	UBERON:0000473	94.47	gold quality
adrenal tissue	UBERON:0018303	93.86	gold quality
right lobe of thyroid gland	UBERON:0001119	93.26	gold quality
adenohypophysis	UBERON:0002196	92.49	gold quality
left lobe of thyroid gland	UBERON:0001120	92.36	gold quality
stromal cell of endometrium	CL:0002255	91.43	gold quality
pituitary gland	UBERON:0000007	91.29	gold quality
thyroid gland	UBERON:0002046	91.21	gold quality
metanephros cortex	UBERON:0010533	91.12	gold quality
ventricular zone	UBERON:0003053	91.08	gold quality
right adrenal gland cortex	UBERON:0035827	90.80	gold quality
right adrenal gland	UBERON:0001233	90.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.44	gold quality
left adrenal gland cortex	UBERON:0035825	90.29	gold quality
left adrenal gland	UBERON:0001234	90.13	gold quality
gastrocnemius	UBERON:0001388	89.61	gold quality
adrenal cortex	UBERON:0001235	89.40	gold quality
islet of Langerhans	UBERON:0000006	89.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.09	gold quality
adrenal gland	UBERON:0002369	89.05	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.69	gold quality
body of uterus	UBERON:0009853	88.67	gold quality
muscle of leg	UBERON:0001383	88.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.39	gold quality
endocervix	UBERON:0000458	88.22	gold quality
ganglionic eminence	UBERON:0004023	88.21	gold quality
corpus callosum	UBERON:0002336	88.16	gold quality
tibial nerve	UBERON:0001323	88.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

109 targeting POMT2, 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-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-3059-5P	99.70	69.93	2491

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 21)

• molecular cloning and characterization (PMID:12460945)
• active enzyme complex of POMT1 and POMT2 suggests that the regulation of protein O-mannosylation is complex and appears to be required for normal structure and function of alpha-dystroglycan in muscle and brain (PMID:14699049)
• POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome [case reports] (PMID:15894594)
• human protein O-mannosyltransferases 1 and 2 form heterocomplexes which possess protein O-mannosyltransferase activity (PMID:16698797)
• Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. (PMID:16887026)
• Our results broaden the clinical spectrum associated with POMT2 mutations, which should be considered in patients with CMD associated with microcephaly, and severe mental retardation with or without ocular involvement. (PMID:17634419)
• identified a POMT2 homozygous missense mutation in a girl with a mild limb-girdle muscular dystrophy (LGMD) phenotype (PMID:17923109)
• testis POMT2 is highly conserved among mammals, including humans, suggesting a crucial function that is distinct from somatic POMT2 (PMID:18490429)
• In pomt2 mutation in CMD patient(three out of 5) show cerebellar hypoplasia. (PMID:18513969)
• Our results indicate that mutations in POMT2 can cause a wide spectrum of clinical phenotypes as observed in other genes associated with alpha-dystroglycanopathy. (PMID:18804929)
• POMT2 intragenic deletions and splicing abnormalities causing congenital muscular dystrophy with mental retardation are reported. (PMID:19138766)
• the N-glycosylation of POMT1 and POMT2 is required for maintaining the conformation as well as the activity of the POMT1-POMT2 complex. (PMID:19880378)
• the function of the gene products is only known for POMT1, POMT2, and POMGnT1, all responsible for the O-mannosylglycan biosynthesis (PMID:20816175)
• the effects of replacing Arg(64), Glu(78) and Arg(138)residues in human POMT1 and POMT2 with Ala on complex formation and enzymatic activity were studied. (PMID:21782786)
• Our report is the first to document an association between POMT2 mutations and aortopathy with concomitant depressed left ventricular systolic function. (PMID:24002165)
• O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to alpha-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. (PMID:28512129)
• POMT2 missense mutation is associated with Cystic kidneys in fetal Walker-Warburg syndrome. (PMID:28815891)
• Muscle biopsy revealed absent alpha-dystroglycan on immunostaining and genetic testing confirmed the diagnosis with two previously described POMT2 mutations. This is the first reported case of WWS syndrome associated with noncompaction cardiomyopathy (PMID:28980384)
• The study expands the mutational spectrum for Limb-girdle Muscular Dystrophy type2N, with the description of 11 novel POMT2 mutations in the association with LGMD2N. (PMID:29175898)
• POMT1 and POMT2 gene mutations result in 2 cases of alpha-dystroglycanopathy.", trans “POMT1POMT22alpha-. (PMID:34565739)
• Clinical exome sequencing identifies novel compound heterozygous mutations of the POMT2 gene in patients with limb-girdle muscular dystrophy. (PMID:36217604)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pomt2	ENSDARG00000055027
mus_musculus	Pomt2	ENSMUSG00000034126
rattus_norvegicus	Pomt2	ENSRNOG00000012146
drosophila_melanogaster	tw	FBGN0086368

Paralogs (3): SDF2L1 (ENSG00000128228), POMT1 (ENSG00000130714), SDF2 (ENSG00000132581)

Protein

Protein identifiers

Protein O-mannosyl-transferase 2 — Q9UKY4 (reviewed: Q9UKY4)

Alternative names: Dolichyl-phosphate-mannose–protein mannosyltransferase 2

All UniProt accessions (34): Q9UKY4, A0A0J9YVW4, A0A804HHT3, A0A804HIA6, A0A804HIE7, A0A804HIH0, A0A804HIM0, A0A804HIP6, A0A804HIS8, A0A804HIT3, A0A804HJ43, A0A804HJB4, A0A804HJG3, A0A804HJH6, A0A804HJH9, A0A804HJN3, A0A804HJS8, A0A804HK17, A0A804HK33, A0A804HKG4, A0A804HKL3, A0A804HKR6, A0A804HKT3, A0A804HKW3, A0A804HKX8, A0A804HKY4, A0A804HL51, A0A804HLA4, A0A804HLC4, A0A804HLK1, H0YJA9, H0YJJ4, H0YJK9, H0YJQ7

UniProt curated annotations — full annotation on UniProt →

Function. Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is insufficient. Essentially dedicated to O-mannosylation of alpha-DAG1 and few other proteins but not of cadherins and protocaherins.

Subunit / interactions. Interacts with POMT1.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in testis; detected at low levels in most tissues.

Post-translational modifications. N-glycosylated.

Disease relevance. Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A2 (MDDGA2) [MIM:613150] 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 congenital with impaired intellectual development B2 (MDDGB2) [MIM:613156] An autosomal recessive disorder characterized by congenital muscular dystrophy associated with intellectual disability and mild structural brain abnormalities. The disease is caused by variants affecting the gene represented in this entry. Muscular dystrophy-dystroglycanopathy limb-girdle C2 (MDDGC2) [MIM:613158] An autosomal recessive muscular dystrophy with onset after ambulation is achieved. MDDGC2 is characterized by increased serum creatine kinase and mild muscle weakness. Muscle biopsy shows dystrophic changes, inflammatory changes, and severely decreased alpha-dystroglycan. Cognition is normal. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Slightly activated by Mg(2+) and inhibited by both Ca(+) and Mn(2+). EDTA ha no effect on activity in vitro.

Pathway. Protein modification; protein glycosylation.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the glycosyltransferase 39 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UKY4-1	1	yes
Q9UKY4-2	2

RefSeq proteins (1): NP_037514* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003342	ArnT-like_N	Domain
IPR016093	MIR_motif	Domain
IPR027005	PMT-like	Family
IPR032421	PMT_4TMC	Domain
IPR036300	MIR_dom_sf	Homologous_superfamily

Pfam: PF02366, PF02815, PF16192

Enzyme classification (BRENDA):

• EC 2.4.1.109 — dolichyl-phosphate-mannose-protein mannosyltransferase (BRENDA: 24 organisms, 130 substrates, 16 inhibitors, 22 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SYNTHETIC PEPTIDE BASED ON A MUCIN-LIKE DOMAIN I	0.63–9.7	5
AC-TYR-ALA-THR-ALA-VAL-NH2	0.25–15	3
RSPSPSTQ	10–20	2
TYR-ASN-PRO-THR-SER-VAL	1–3.3	2
AC-ALA-THR-ALA-NH2	6.7	1
AC-TYR-ASN-PRO-THR-SER-VAL-NH2	4.3	1
BIOTIN-TYR-LEU-ALA-VAL-NH2	0.1	1
BIOTIN-TYR-PRO-THR-ALA-VAL-NH2	0.85	1
BIOTIN-TYR-THR-ALA-VAL-NH2	0.075	1
DOLICHYL PHOSPHATE D-MANNOSE	0.4	1
TYR-ALA-THR-ALA-VAL	2.2	1
TYR-LEU-THR-ALA-VAL	2.5	1
TYR-PRO-THR-ALA-VAL	7.3	1

Catalyzed reactions (Rhea), 2 shown:

• a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate + L-seryl-[protein] = 3-O-(alpha-D-mannosyl)-L-seryl-[protein] + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:17377)
• a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate + L-threonyl-[protein] = 3-O-(alpha-D-mannosyl)-L-threonyl-[protein] + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:53396)

UniProt features (38 total): sequence variant 15, transmembrane region 10, glycosylation site 5, domain 3, chain 1, region of interest 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKY4-F1	87.96	0.68

Functional residue map

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

Post-translational modifications (1): 41

Glycosylation sites (5): 98, 330, 445, 528, 583

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-5083629	Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2
R-HSA-5083633	Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1
R-HSA-8932504	DAG1 core M2 glycosylations
R-HSA-8932505	DAG1 core M3 glycosylations
R-HSA-8932506	DAG1 core M1 glycosylations
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane

MSigDB gene sets: 418 (showing top): GOBP_DENTATE_GYRUS_DEVELOPMENT, GCM_MAP4K4, GCM_PTPRD, GOBP_INFLAMMATORY_RESPONSE, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, chr14q24, GOBP_HIPPOCAMPUS_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_PALLIUM_DEVELOPMENT, GOBP_HEAD_DEVELOPMENT, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, DANG_BOUND_BY_MYC, GOBP_TELENCEPHALON_DEVELOPMENT

GO Biological Process (6): dentate gyrus development (GO:0021542), protein O-linked glycosylation via mannose (GO:0035269), basement membrane organization (GO:0071711), reactive gliosis (GO:0150103), obsolete protein glycosylation (GO:0006486), protein O-linked glycosylation (GO:0006493)

GO Molecular Function (5): mannosyltransferase activity (GO:0000030), dolichyl-phosphate-mannose-protein mannosyltransferase activity (GO:0004169), metal ion binding (GO:0046872), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (7): nucleoplasm (GO:0005654), nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
DAG1 glycosylations	3
Diseases associated with O-glycosylation of proteins	2
Regulation of CDH1 Expression and Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
nuclear lumen	2
cytoplasm	2
hippocampus development	1
anatomical structure development	1
protein O-linked glycosylation	1
extracellular matrix organization	1
neuroinflammatory response	1
glycoprotein biosynthetic process	1
hexosyltransferase activity	1
mannosyltransferase activity	1
protein O-linked glycosylation via mannose	1
catalytic activity, acting on a protein	1
cation binding	1
catalytic activity	1
transferase activity	1
intracellular membraneless organelle	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1138 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POMT2	POMGNT1	Q8WZA1	987
POMT2	FKTN	O75072	986
POMT2	FKRP	Q9H9S5	986
POMT2	DAG1	Q14118	970
POMT2	POMT1	Q9Y6A1	966
POMT2	POMGNT2	Q8NAT1	873
POMT2	RXYLT1	Q9Y2B1	855
POMT2	LARGE1	O95461	854
POMT2	B3GALNT2	Q8NCR0	851
POMT2	POMK	Q9H5K3	846
POMT2	GMPPB	Q9Y5P6	826
POMT2	DPM3	Q9P2X0	810
POMT2	SGCB	Q16585	785
POMT2	DOLK	Q9UPQ8	771
POMT2	B4GAT1	O43505	755

IntAct

69 interactions, top by confidence:

A	B	Type	Score
HLA-DRA	HLA-DRB1	psi-mi:“MI:0914”(association)	0.880
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
FDFT1	USP32	psi-mi:“MI:0914”(association)	0.530
PCDHB16	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
GABRA3	HLA-C	psi-mi:“MI:0914”(association)	0.530
CD300E	SPPL2B	psi-mi:“MI:0914”(association)	0.530
CD244	MTX2	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
POMT1	POMT2	psi-mi:“MI:0915”(physical association)	0.460
POMT1	POMT2	psi-mi:“MI:0403”(colocalization)	0.460
UPK1A	TMEM223	psi-mi:“MI:0914”(association)	0.350
TMED6	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
ASIC4	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
LRRC4	MID1	psi-mi:“MI:0914”(association)	0.350
HTR3A	GPAA1	psi-mi:“MI:0914”(association)	0.350
CHRND	EXTL3	psi-mi:“MI:0914”(association)	0.350
CD244	CAND2	psi-mi:“MI:0914”(association)	0.350
PON2	ENTPD6	psi-mi:“MI:0914”(association)	0.350
RFTN2	NMT1	psi-mi:“MI:0914”(association)	0.350
TMEM92	NEDD4	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), POMT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, B0BNG2, O60725, O75908, O77759, O88269, O88908, O95255, Q0P4J9, Q290J8, Q3T1L5, Q3TAE8, Q3UV71, Q499P8, Q49LS7, Q4R4E1, Q4VV71, Q5F380, Q5KR61, Q5R8F6, Q5RAH7, Q5RKL5, Q6AZ83, Q6NVG1, Q7SXZ1, Q7T310, Q7TPN3, Q7TQM4, Q86VD9, Q8AVI9, Q8BTP0, Q8C0T0, Q8C3X8, Q8CI59, Q8IUR5, Q8K2A8, Q8L638, Q8R1J1, Q8R4P9

Diamond homologs: F1Q8R9, F1QF89, O13898, O74189, P31382, P33775, P42934, P46971, P47190, P52867, Q29IL2, Q2LZ62, Q3SZ45, Q54P23, Q59X23, Q5A688, Q5ACU3, Q5ADM9, Q8BGQ4, Q8R2R1, Q93ZE8, Q99470, Q99PR0, Q9C100, Q9DCT5, Q9UKY4, Q9VTK2, Q9W5D4, Q9Y6A1, O42933, Q3T083, Q9ESP1, Q9HCN8, A0R3E8, L8F4Z2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POMT2	“form complex”	POMT	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Neurotransmitter receptors and postsynaptic signal transmission	7	13.0×	5e-05
Interferon gamma signaling	5	11.6×	2e-03
Transmission across Chemical Synapses	7	9.9×	3e-04
Neuronal System	7	5.7×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
acetylcholine receptor signaling pathway	5	40.5×	3e-05
membrane depolarization	5	33.2×	6e-05
monoatomic ion transmembrane transport	9	24.3×	6e-08
regulation of membrane potential	6	18.0×	1e-04
chemical synaptic transmission	7	7.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1307 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	71
Likely pathogenic	63
Uncertain significance	476
Likely benign	500
Benign	68

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070813	NM_013382.7(POMT2):c.1034_1035del (p.Val345fs)	Pathogenic
1073316	NM_013382.7(POMT2):c.1237C>T (p.Arg413Ter)	Pathogenic
1074015	NM_013382.7(POMT2):c.1555G>T (p.Glu519Ter)	Pathogenic
1323490	NM_013382.7(POMT2):c.1940G>A (p.Trp647Ter)	Pathogenic
1416054	NM_013382.7(POMT2):c.1300del (p.Arg434fs)	Pathogenic
1433335	NM_013382.7(POMT2):c.879_880del (p.Thr295fs)	Pathogenic
162599	NM_013382.7(POMT2):c.1484+1G>T	Pathogenic
166902	NM_013382.7(POMT2):c.1726-2A>G	Pathogenic
1969838	NM_013382.7(POMT2):c.1130T>A (p.Leu377Ter)	Pathogenic
2033046	NM_013382.7(POMT2):c.1981del (p.Leu661fs)	Pathogenic
2089840	NM_013382.7(POMT2):c.524_533del (p.Leu175fs)	Pathogenic
211950	NM_013382.7(POMT2):c.1577-5_1577-1delinsTGA	Pathogenic
2122163	NM_013382.7(POMT2):c.70dup (p.Gln24fs)	Pathogenic
2420326	NM_013382.7(POMT2):c.1243G>T (p.Glu415Ter)	Pathogenic
242416	NM_013382.5(POMT2):c.1170_1171del	Pathogenic
2425862	NC_000014.8:g.(?77755085)(77762636_?)del	Pathogenic
2431196	NM_013382.7(POMT2):c.437del (p.Gly146fs)	Pathogenic
2437987	NM_013382.7(POMT2):c.1159del (p.Ile387fs)	Pathogenic
281068	NM_013382.7(POMT2):c.1045_1052delinsG (p.Arg349fs)	Pathogenic
282447	NM_013382.7(POMT2):c.1123_1124dup (p.Tyr376fs)	Pathogenic
289765	NM_013382.7(POMT2):c.924-2A>G	Pathogenic
2921970	NM_013382.7(POMT2):c.2147+1G>A	Pathogenic
2922185	NM_013382.7(POMT2):c.118_119del (p.Arg40fs)	Pathogenic
2923402	NM_013382.7(POMT2):c.1768dup (p.Tyr590fs)	Pathogenic
2923579	NM_013382.7(POMT2):c.1927_1943del (p.Val643fs)	Pathogenic
2923998	NM_013382.7(POMT2):c.1661del (p.Ser554fs)	Pathogenic
2924951	NM_013382.7(POMT2):c.1051del (p.Ala351fs)	Pathogenic
2925744	NM_013382.7(POMT2):c.1158dup (p.Ile387fs)	Pathogenic
2927141	NM_013382.7(POMT2):c.1911_1912delinsGT (p.Arg638Ter)	Pathogenic
2929004	NM_013382.7(POMT2):c.1046_1052del (p.Arg349fs)	Pathogenic

SpliceAI

3946 predictions. Top by Δscore:

Variant	Effect	Δscore
14:77283795:AC:A	donor_gain	1.0000
14:77283796:CC:C	donor_gain	1.0000
14:77283872:CA:C	acceptor_gain	1.0000
14:77283874:C:CC	acceptor_gain	1.0000
14:77284944:A:AC	donor_gain	1.0000
14:77284945:C:CC	donor_gain	1.0000
14:77284948:A:AC	donor_gain	1.0000
14:77284949:C:CC	donor_gain	1.0000
14:77284949:CA:C	donor_gain	1.0000
14:77285480:CCA:C	donor_gain	1.0000
14:77285631:TT:T	acceptor_gain	1.0000
14:77285633:C:A	acceptor_loss	1.0000
14:77285633:C:CC	acceptor_gain	1.0000
14:77285637:CA:C	acceptor_gain	1.0000
14:77285638:A:C	acceptor_gain	1.0000
14:77285646:C:CT	acceptor_gain	1.0000
14:77285646:C:T	acceptor_gain	1.0000
14:77285647:A:T	acceptor_gain	1.0000
14:77286738:A:AC	donor_gain	1.0000
14:77286739:C:CC	donor_gain	1.0000
14:77286739:CTTA:C	donor_gain	1.0000
14:77286740:TTA:T	donor_loss	1.0000
14:77286741:TA:T	donor_loss	1.0000
14:77286742:A:AC	donor_gain	1.0000
14:77286743:C:CT	donor_gain	1.0000
14:77286743:CT:C	donor_gain	1.0000
14:77286743:CTATG:C	donor_gain	1.0000
14:77286819:AGTT:A	acceptor_gain	1.0000
14:77286820:GTT:G	acceptor_gain	1.0000
14:77286821:TT:T	acceptor_gain	1.0000

AlphaMissense

4868 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:77278771:G:C	H664D	0.999
14:77280409:A:G	W570R	0.999
14:77280409:A:T	W570R	0.999
14:77284980:A:G	W516R	0.999
14:77284980:A:T	W516R	0.999
14:77285014:G:C	C504W	0.999
14:77285605:A:G	W454R	0.999
14:77285605:A:T	W454R	0.999
14:77286801:A:C	S425R	0.999
14:77286801:A:T	S425R	0.999
14:77286803:T:G	S425R	0.999
14:77291344:A:G	W385R	0.999
14:77291344:A:T	W385R	0.999
14:77291348:G:C	N383K	0.999
14:77291348:G:T	N383K	0.999
14:77296211:A:G	S357P	0.999
14:77312015:A:C	F89L	0.999
14:77312015:A:T	F89L	0.999
14:77312017:A:G	F89L	0.999
14:77312025:T:A	E86V	0.999
14:77312028:T:A	D85V	0.999
14:77312028:T:C	D85G	0.999
14:77312028:T:G	D85A	0.999
14:77312029:C:G	D85H	0.999
14:77312030:C:A	W84C	0.999
14:77312030:C:G	W84C	0.999
14:77280034:A:G	L591P	0.998
14:77285015:C:T	C504Y	0.998
14:77285016:A:G	C504R	0.998
14:77285482:A:G	W495R	0.998

dbSNP variants (sampled 300 via entrez): RS1000032443 (14:77298896 G>A,C,T), RS1000052812 (14:77308050 C>T), RS1000159601 (14:77301535 T>C), RS1000262755 (14:77291220 C>T), RS1000357198 (14:77295557 G>A), RS1000374576 (14:77313339 T>C), RS1000388278 (14:77295406 G>A), RS1000417413 (14:77297874 T>A,C), RS1000450287 (14:77295740 G>T), RS1000555239 (14:77310713 C>A,G,T), RS1000673491 (14:77282334 C>T), RS1000684156 (14:77316565 C>G,T), RS1000783888 (14:77318018 G>A,C,T), RS1000790982 (14:77322011 G>A,T), RS1000876474 (14:77277125 C>G,T)

Disease associations

OMIM: gene MIM:607439 | disease phenotypes: MIM:613150, MIM:613156, MIM:613158, MIM:236670, MIM:253600

GenCC curated gene-disease

Disease	Classification	Inheritance
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2	Definitive	Autosomal recessive
myopathy caused by variation in POMT2	Strong	Autosomal recessive
muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2	Moderate	Autosomal recessive
autosomal recessive limb-girdle muscular dystrophy type 2N	Supportive	Autosomal recessive
congenital muscular dystrophy with cerebellar involvement	Supportive	Autosomal recessive
congenital muscular dystrophy with intellectual disability	Supportive	Autosomal recessive
muscle-eye-brain disease	Supportive	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 POMT2	Definitive	AR

Mondo (12): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 (MONDO:0013154), muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (MONDO:0013160), autosomal recessive limb-girdle muscular dystrophy type 2N (MONDO:0013162), muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (MONDO:0009364), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), myopathy caused by variation in POMT2 (MONDO:0700071), muscular dystrophy (MONDO:0020121), intellectual disability (MONDO:0001071), (MONDO:0018277), congenital muscular dystrophy with intellectual disability (MONDO:0018278), muscle-eye-brain disease (MONDO:0018939), muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171)

Orphanet (7): POMT2-related limb-girdle muscular dystrophy R14 (Orphanet:206559), Muscle-eye-brain disease (Orphanet:588), Walker-Warburg syndrome (Orphanet:899), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Muscular dystrophy (Orphanet:98473), Congenital muscular alpha-dystroglycanopathy with brain and eye anomalies (Orphanet:352687), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

181 total (30 of 181 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000050	Hypoplastic male external genitalia
HP:0000054	Micropenis
HP:0000110	Renal dysplasia
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000194	Open mouth
HP:0000204	Cleft upper lip
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000298	Mask-like facies
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000413	Atresia of the external auditory canal
HP:0000478	Abnormality of the eye
HP:0000482	Microcornea
HP:0000485	Megalocornea
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000525	Abnormality iris morphology
HP:0000528	Anophthalmia

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
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
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7972	GSTZ1, POMT2		0.00	0
rs7975	GSTZ1, POMT2		0.00	0
rs1046428	GSTZ1, POMT2		0.00	0

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	4
sodium arsenite	increases abundance, increases expression, increases reaction	2
FR900359	increases phosphorylation	1
quercitrin	increases expression	1
beta-lapachone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression, affects cotreatment	1
Microplastics	increases expression, increases reaction, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Polystyrenes	increases abundance, increases expression, increases reaction	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

7 cell lines: 3 finite cell line, 2 induced pluripotent stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_AZ52	GM24374	Finite cell line	Female
CVCL_AZ53	GM24375	Finite cell line	Male
CVCL_BX12	GM23824	Finite cell line	Female
CVCL_C7L6	GM27939	Induced pluripotent stem cell	Female
CVCL_F0ZD	GM29471	Induced pluripotent stem cell	Female
CVCL_TF22	HAP1 POMT2 (-) 1	Cancer cell line	Male
CVCL_TF23	HAP1 POMT2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01882400	PHASE4	COMPLETED	Assessment of Response to Treatment of Osteoporosis With Oral Bisphosphonates in Patients With Muscular Dystrophy
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01254019	PHASE3	COMPLETED	A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01480245	PHASE3	TERMINATED	Open Label Study of GSK2402968 in Subjects With Duchenne Muscular Dystrophy
NCT01803412	PHASE3	TERMINATED	A Study of the Safety, Tolerability & Efficacy of Long-term Administration of Drisapersen in US & Canadian Subjects
NCT01826487	PHASE3	COMPLETED	Phase 3 Study of Ataluren in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)
NCT01890798	PHASE3	WITHDRAWN	Drisapersen Duchenne Muscular Dystrophy (DMD) Treatment Protocol
NCT02090959	PHASE3	TERMINATED	An Extension Study of Ataluren (PTC124) in Participants With Nonsense Mutation Dystrophinopathy
NCT02432885	PHASE3	COMPLETED	Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy - ACE Inhibitor Therapy Trial
NCT03179631	PHASE3	COMPLETED	Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
NCT05126758	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping
NCT07608432	PHASE3	RECRUITING	Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO)
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01153932	PHASE2	COMPLETED	Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy
NCT01462292	PHASE2	COMPLETED	A Clinical Study to Assess Two Doses of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD)
NCT01910649	PHASE2	TERMINATED	A Phase I/II, Open Label, Escalating Dose, Pilot Study to Assess Effect, Safety, Tolerability and PK of Multiple SC Doses of Drisapersen in Patients With Duchenne Muscular Dystrophy and to Assess the Potential for IV Dosing as an Alternative Route of Administration
NCT03406780	PHASE2	COMPLETED	A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy
NCT05479981	PHASE2	COMPLETED	Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients
NCT06290713	PHASE2	RECRUITING	Vasodilator and Exercise Study for DMD (VASO-REx)
NCT06547216	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Open-label Extension Study of AOC 1020 in Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
NCT07287189	PHASE2	RECRUITING	Phase 2 Study of SAT-3247 in Pediatric Ambulatory Patients
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00494195	PHASE1	COMPLETED	Gene Transfer Therapy for Treating Children and Adults With Limb Girdle Muscular Dystrophy Type 2D (LGMD2D)
NCT00674843	PHASE1	UNKNOWN	The Efficacy of Using Far Infrared Radiation to Manage Muscular Dystrophies
NCT00873782	PHASE1	COMPLETED	Safety Study of Transvenous Limb Perfusion in Human Muscular Dystrophy
NCT01128855	PHASE1	COMPLETED	A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects
NCT02241928	PHASE1	WITHDRAWN	Stem Cell Therapy in Muscular Dystrophy
NCT03627494	PHASE1	COMPLETED	First Time in Human (FTIH) Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of GSK3439171A in Healthy Subjects and to Assess Food Effect
NCT05492734	PHASE1	COMPLETED	A Study to Assess the Feasibility of Non-invasive Dried Blood Sampling
NCT05730842	PHASE1	COMPLETED	Absorption, Metabolism, Excretion and Absolute Bioavailability of EDG-5506 in Healthy Volunteers
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism