POMK

protein O-mannose kinase

Basic information

Region (hg38): 8:43093498-43131180

Links

ENSG00000185900 ∙ NCBI:84197 ∙ OMIM:615247 ∙ HGNC:26267 ∙ Uniprot:Q9H5K3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (Strong), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (Moderate), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy, type A (Supportive), mode of inheritance: AR
• congenital muscular dystrophy with cerebellar involvement (Supportive), mode of inheritance: AR
• limb-girdle muscular dystrophy due to POMK deficiency (Supportive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A, 12; Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type C, 12; Muscle-eye brain disease; Walker-Warburg syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic; Ophthalmologic	23519211; 24556084; 24925318

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POMK gene.

• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency (8 variants)
• Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (5 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (2 variants)
• not provided (1 variants)
• Limb-girdle muscular dystrophy due to POMK deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POMK gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				65	2	67
missense			121	5		126
nonsense	5	2				7
start loss			2			2
frameshift	9	4				13
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region				4	1	5
non coding				8	5	13
Total	15	6	123	78	7

Highest pathogenic variant AF is 0.0000131

Variants in POMK

This is a list of pathogenic ClinVar variants found in the POMK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-43093551-G-T			Likely benign (Apr 09, 2018)
8-43097519-TAAAG-T		not specified	Benign (May 23, 2016)
8-43103230-T-G			Likely benign (May 14, 2019)
8-43103459-A-G			Likely benign (Jul 21, 2018)
8-43103549-A-G		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Uncertain significance (Feb 24, 2022)
8-43103551-G-C		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Uncertain significance (Oct 04, 2022)
8-43103558-C-T		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Pathogenic/Likely pathogenic (Dec 22, 2022)
8-43103568-A-G		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency	Conflicting classifications of pathogenicity (Dec 06, 2023)
8-43103572-C-T		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Likely benign (Apr 21, 2022)
8-43103576-A-G		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Uncertain significance (Oct 15, 2020)
8-43103581-C-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency	Likely benign (Aug 03, 2023)
8-43103581-C-G		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Likely benign (Dec 13, 2018)
8-43103584-C-T		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Likely benign (Aug 09, 2022)
8-43103585-G-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency	Uncertain significance (Aug 07, 2023)
8-43103585-G-GC		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Pathogenic/Likely pathogenic (Mar 18, 2022)
8-43103586-C-T			Uncertain significance (Jun 26, 2020)
8-43103587-C-G		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency	Likely benign (Sep 24, 2021)
8-43103587-C-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency	Likely benign (Feb 28, 2022)
8-43103591-C-G		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency	Uncertain significance (Jul 06, 2022)
8-43103591-C-T		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Pathogenic (Nov 25, 2023)
8-43103592-G-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12;Limb-girdle muscular dystrophy due to POMK deficiency • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 27, 2023)
8-43103592-G-T		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 • Inborn genetic diseases	Uncertain significance (Apr 11, 2023)
8-43103593-A-G		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Likely benign (Jul 06, 2022)
8-43103594-G-A		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 • Inborn genetic diseases	Uncertain significance (Jun 19, 2022)
8-43103595-A-G		Limb-girdle muscular dystrophy due to POMK deficiency;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12	Uncertain significance (Aug 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POMK	protein_coding	protein_coding	ENST00000331373	2	29920

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.95e-8	0.139	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.469	178	196	0.906	0.0000104	2310
Missense in Polyphen		42	59.572	0.70503		724
Synonymous	-0.421	88	83.1	1.06	0.00000499	690
Loss of Function	0.0725	12	12.3	0.978	7.59e-7	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.000693	0.000693
European (Non-Finnish)	0.000317	0.000316
Middle Eastern	0.000217	0.000217
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N- acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine- beta-1,3-N-acetylglucosamine-beta-1,4-(phosphate-6-)mannose). Phosphorylated O-mannosyl trisaccharide is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Only shows kinase activity when the GalNAc-beta-3-GlcNAc-beta-terminus is linked to the 4-position of O-mannose, suggesting that this disaccharide serves as the substrate recognition motif. {ECO:0000269|PubMed:23519211, ECO:0000269|PubMed:23929950}.
• Disease: DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C12 (MDDGC12) [MIM:616094]: An autosomal recessive limb-girdle congenital muscular dystrophy, characterized by muscle weakness and delayed motor development in association with cognitive impairment. {ECO:0000269|PubMed:24925318}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mannose type O-glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;O-linked glycosylation (Consensus)

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.174
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pomk
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype

Zebrafish Information Network

• Gene name: pomk
• Affected structure: muscle
• Phenotype tag: abnormal
• Phenotype quality: dystrophic

Gene ontology

• Biological process: neuron migration;protein phosphorylation;protein O-linked glycosylation;brain development;learning or memory;sensory perception of pain;carbohydrate phosphorylation;neuromuscular process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: protein kinase activity;ATP binding;phosphotransferase activity, alcohol group as acceptor;carbohydrate kinase activity