SHPK

protein-coding

sedoheptulokinase

Gene summary

The protein encoded by this gene has weak homology to several carbohydrate kinases, a class of proteins involved in the phosphorylation of sugars as they enter a cell, inhibiting return across the cell membrane. Sequence variation between this novel gene and known carbohydrate kinases suggests the possibility of a different substrate, cofactor or changes in kinetic properties distinguishing it from other carbohydrate kinases. The gene resides in a region commonly deleted in cystinosis patients, suggesting a role as a modifier for the cystinosis phenotype. The genomic region is also rich in Alu repetitive sequences, frequently involved in chromosomal rearrangements. [provided by RefSeq, Jul 2008]

Previous symbols:

CARKL

MANE transcript

NM_013276.4

Inheritance

ClinVar variants

U:148B:80

Top phenotype

Sedoheptulokinase deficiency

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr17:3,608,240-3,636,250

External References & Databases

Ensembl (ENSG00000197417)

Transcript & Mutation Effects

hg38 • Region Span ~28.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

isolated sedoheptulokinase deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014969

Submitter: PanelApp Australia

isolated sedoheptulokinase deficiencyLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014969

Submitter: Labcorp Genetics (formerly Invitae)

isolated sedoheptulokinase deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014969

Submitter: Ambry Genetics

isolated sedoheptulokinase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014969

Submitter: Orphanet

Clinical Genomic Database (CGD)

Sedoheptulokinase deficiencyAR

Manifestation: Biochemical

Intervention: General

Rationale: The clinical relevance is unclear

Refs: 25647543

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHPK variants in ClinVar

4 Conditions Cataloged

not providedTotal: 208

not specifiedTotal: 83

SHPK-related disorderTotal: 4

Isolated sedoheptulokinase deficiencyTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013276.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				65 clinvar	4 clinvar	69
missense			134 clinvar	8 clinvar	3 clinvar	145
nonsense			5 clinvar			5
start loss						0
frameshift			8 clinvar			8
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	148	73	7	228

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013276.4	RefSeq	NP_037408.2	7	MANE Select
ENST00000225519.5	Ensembl	ENSP00000225519.3	7	MANE Select
ENST00000983149.1	Ensembl	ENSP00000652966.1	6	Standard
ENST00001084080.1	Ensembl	ENSP00000753886.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pentose phosphate pathway (hexose monophosphate shunt)
Metabolism of carbohydrates
Metabolism

Biological Process

carbohydrate metabolic process
pentose-phosphate shunt
pentose-phosphate shunt, non-oxidative branch
phosphorylation
cellular response to interleukin-13

Molecular Function

ATP binding
sedoheptulokinase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000225519
Coding exons: 7
Length: 28061
Individuals with no LoFs: 125495
Homozygous LoFs: 1
Heterozygous LoFs: 251
Defined: 125747
p: 0.00100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.166	303	295	1.03	0.0000178	3067
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.0012	0.0012	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.00098	0.00098	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

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.;

Intolerance Scores

RVIS EVS: -0.4
RVIS percentile EVS: 26.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.977

Gene Damage Prediction

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