GeneBe

POMK

protein-coding

protein O-mannose kinase

Gene summary

This gene encodes a protein that may be involved in the presentation of the laminin-binding O-linked carbohydrate chain of alpha-dystroglycan (a-DG), which forms transmembrane linkages between the extracellular matrix and the exoskeleton. Some pathogens use this O-linked carbohydrate unit for host entry. Loss of function compound heterozygous mutations in this gene were found in a human patient affected by the Walker-Warburg syndrome (WWS) phenotype. Mice lacking this gene contain misplaced neurons (heterotopia) in some regions of the brain, possibly from defects in neuronal migration. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

MANE transcript

NM_032237.5

Inheritance

AR, AD

ClinVar variants

P:31U:149B:87

Top phenotype

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

gnomAD constraint

pLI —, LoF o/e 0.98

Max pathogenic AF

—

Genomic locus

chr8:43,093,498-43,131,180

External References & Databases

Ensembl (ENSG00000185900)NCBI Gene (84197)OMIM (615247)HGNC:26267GenCCUniProt (Q9H5K3)AlphaFoldClinVar (POMK)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~37.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014101

Submitter: Labcorp Genetics (formerly Invitae)

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014101

Submitter: Genomics England PanelApp

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014101

Submitter: Ambry Genetics

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014101

Submitter: PanelApp Australia

anterior segment dysgenesisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019503

Submitter: PanelApp Australia

congenital muscular dystrophy with cerebellar involvementSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018277

Submitter: Orphanet

muscular dystrophy-dystroglycanopathy, type ASUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0000171

Submitter: Orphanet

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014101

Submitter: G2P

limb-girdle muscular dystrophy due to POMK deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014489

Submitter: Orphanet

Clinical Genomic Database (CGD)

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 syndromeAR

Manifestation: Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 23519211; 24556084; 24925318Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POMK variants in ClinVar

6 Conditions Cataloged
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12Total: 238
Limb-girdle muscular dystrophy due to POMK deficiencyTotal: 235
not providedTotal: 80
Inborn genetic diseasesTotal: 47
not specifiedTotal: 16
POMK-related disorderTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032237.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
73
clinvar
2
clinvar
 75
missense
1
clinvar
2
clinvar
145
clinvar
12
clinvar
 160
nonsense
4
clinvar
4
clinvar
1
clinvar
 9
start loss
1
clinvar
1
clinvar
 2
frameshift
13
clinvar
5
clinvar
2
clinvar
 20
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total1912149852267

Highest pathogenic variant AF is 0.00008054233

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_032237.5RefSeqNP_115613.12MANE Select
ENST00000331373.10EnsemblENSP00000331258.52MANE Select
NM_001277971.2RefSeqNP_001264900.12Standard
ENST00000518991.6EnsemblENSP00000429090.21Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
pomkDanio rerio

Structure: muscle

Quality: dystrophic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Mannose type O-glycan biosynthesis - Homo sapiens (human)
  • Post-translational protein modification
  • Metabolism of proteins
  • O-linked glycosylation

Biological Process

  • neuron migration
  • protein phosphorylation
  • protein O-linked glycosylation
  • brain development
  • learning or memory

Molecular Function

  • protein kinase activity
  • ATP binding
  • phosphotransferase activity, alcohol group as acceptor
  • carbohydrate kinase activity

Cellular Component

  • endoplasmic reticulum membrane
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000331373
Coding exons
2
Length
29920
Individuals with no LoFs
125682
Homozygous LoFs
0
Heterozygous LoFs
66
Defined
125748
p
0.000262
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.4691781960.9060.00001042310
Missense (PolyPhen)4259.5720.70503724
Synonymous-0.4218883.11.060.00000499690
Loss of Function0.07251212.30.9787.59e-7122

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian0.000220.00022rare
Finnish0.000690.00069rare
European (Non-Finnish)0.000320.00032rare
South Asian0.0000980.000098rare
Other0.000330.00033rare

dbNSFP Gene Annotations

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.;

Essentials

Essential (CRISPR)
N
Essential (gene trap)
N

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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