SHPK

sedoheptulokinase

Basic information

Region (hg38): 17:3608240-3636250

Previous symbols: [ "CARKL" ]

Links

ENSG00000197417 ∙ NCBI:23729 ∙ OMIM:605060 ∙ HGNC:1492 ∙ Uniprot:Q9UHJ6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated sedoheptulokinase deficiency (Supportive), mode of inheritance: AR
• isolated sedoheptulokinase deficiency (Limited), mode of inheritance: AR
• isolated sedoheptulokinase deficiency (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sedoheptulokinase deficiency	AR	General	The clinical relevance is unclear	Biochemical	25647543

ClinVar

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

• not_provided (185 variants)
• not_specified (68 variants)
• SHPK-related_disorder (3 variants)
• Isolated_sedoheptulokinase_deficiency (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHPK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000013276.4. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				56	4	60
missense			117	7	3	127
nonsense			3			3
start loss						0
frameshift			7			7
splice donor/acceptor (+/-2bp)			1			1
Total	0	0	128	63	7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHPK	protein_coding	protein_coding	ENST00000225519	7	28061

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.22e-13	0.0666	125495	1	251	125747	0.00100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.166	303	295	1.03	0.0000178	3067
Missense in Polyphen		114	106.54	1.0701		1112
Synonymous	-0.724	145	134	1.08	0.00000952	1034
Loss of Function	0.438	20	22.2	0.900	0.00000140	196

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00192	0.00192
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.000231	0.000231
European (Non-Finnish)	0.00137	0.00135
Middle Eastern	0.000218	0.000217
South Asian	0.000984	0.000980
Other	0.000979	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a modulator of macrophage activation through control of glucose metabolism. {ECO:0000250}.
• Disease: DISEASE: Sedoheptulokinase deficiency (SHPKD) [MIM:617213]: An autosomal recessive metabolic disease characterized by increased urinary erythritol and sedoheptulose. Neonatal cholestasis, hypoglycemia, anemia, congenital arthrogryposis multiplex, multiple contractures and dysmorphisms have been reported in SHPKD patients, but the relationship of these features to the SHPKD is unclear. {ECO:0000269|PubMed:25647543}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pentose phosphate pathway (hexose monophosphate shunt);Metabolism of carbohydrates;Metabolism (Consensus)

Intolerance Scores

• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.93

Haploinsufficiency Scores

• pHI: 0.104
• hipred: N
• hipred_score: 0.167
• ghis: 0.384

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.977

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Shpk

Gene ontology

• Biological process: carbohydrate metabolic process;pentose-phosphate shunt;pentose-phosphate shunt, non-oxidative branch;phosphorylation;cellular response to interleukin-13;regulation of macrophage activation;regulation of inflammatory response;cellular response to lipopolysaccharide;cellular response to interleukin-4
• Cellular component: cytoplasm;cytosol
• Molecular function: ATP binding;sedoheptulokinase activity