GeneBe

ALPK1

alpha kinase 1

Basic information

Region (hg38): 4:112285509-112442621

Links

ENSG00000073331 ∙ NCBI:80216 ∙ OMIM:607347 ∙ HGNC:20917 ∙ Uniprot:Q96QP1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (Strong), mode of inheritance: AD
  • retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (Supportive), mode of inheritance: AD
  • retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (Strong), mode of inheritance: AD
  • retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndromeADGastrointestinalThe condition can include splenomegaly and related sequelae, such as cytopenia, and splenectomy has been described as being indicated in some individualsGastrointestinal; Hematologic; Neurologic; Ophthalmologic22307799; 30967659; 31939038

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALPK1 gene.

  • not_provided (719 variants)
  • Inborn_genetic_diseases (167 variants)
  • ALPK1-related_disorder (18 variants)
  • Retinal_dystrophy,_optic_nerve_edema,_splenomegaly,_anhidrosis,_and_migraine_headache_syndrome (14 variants)
  • not_specified (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALPK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000025144.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
150
clinvar
19
clinvar
 173
missense
2
clinvar
1
clinvar
397
clinvar
63
clinvar
28
clinvar
 491
nonsense
11
clinvar
2
clinvar
1
clinvar
 14
start loss
0
frameshift
26
clinvar
4
clinvar
2
clinvar
 32
splice donor/acceptor (+/-2bp)
4
clinvar
 4
Total 2 1 442 219 50

Highest pathogenic variant AF is 6.84297e-7

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ALPK1protein_codingprotein_codingENST00000458497 14157112
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.02e-190.58612503937061257480.00282
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.2826806601.030.00003458162
Missense in Polyphen188192.660.97582431
Synonymous0.4672542640.9630.00001562369
Loss of Function1.983853.60.7090.00000258656

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.01090.0110
Ashkenazi Jewish0.0002980.000298
East Asian0.01360.0134
Finnish0.001160.00116
European (Non-Finnish)0.001290.00127
Middle Eastern0.01360.0134
South Asian0.002330.00232
Other0.002130.00212

dbNSFP

Source: dbNSFP

Function
FUNCTION: Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity (PubMed:28877472, PubMed:28222186, PubMed:30111836). Specifically recognizes and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria (PubMed:30111836). ADP-Heptose-binding stimulates its kinase activity to phosphorylate and activate TIFA, triggering proinflammatory NF-kappa-B signaling (PubMed:30111836). May be involved in monosodium urate monohydrate (MSU)-induced inflammation by mediating phosphorylation of unconventional myosin MYO9A (PubMed:27169898). May also play a role in apical protein transport by mediating phosphorylation of unconventional myosin MYO1A (PubMed:15883161). {ECO:0000269|PubMed:15883161, ECO:0000269|PubMed:27169898, ECO:0000269|PubMed:28222186, ECO:0000269|PubMed:28877472, ECO:0000269|PubMed:30111836}.;

Recessive Scores

pRec
0.0958

Intolerance Scores

loftool
0.955
rvis_EVS
1.46
rvis_percentile_EVS
95.18

Haploinsufficiency Scores

pHI
0.134
hipred
N
hipred_score
0.233
ghis
0.461

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
gene_indispensability_pred
E
gene_indispensability_score
0.505

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Alpk1
Phenotype

Gene ontology

Biological process
cytoplasmic pattern recognition receptor signaling pathway;protein phosphorylation;positive regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response
Cellular component
cytosol
Molecular function
protein serine/threonine kinase activity;protein binding;ATP binding;monosaccharide binding