Isolated sedoheptulokinase deficiency

Summary

Isolated sedoheptulokinase deficiency (MONDO:0014969) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 28

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0001371	Flexion contracture	Obligate (100%)
HP:0002804	Arthrogryposis multiplex congenita	Obligate (100%)
HP:0012768	Neonatal asphyxia	Obligate (100%)
HP:0000023	Inguinal hernia	Frequent (30-79%)
HP:0000083	Renal insufficiency	Frequent (30-79%)
HP:0000091	Abnormal renal tubule morphology	Frequent (30-79%)
HP:0000239	Large fontanelles	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000348	High forehead	Frequent (30-79%)
HP:0000586	Shallow orbits	Frequent (30-79%)
HP:0000601	Hypotelorism	Frequent (30-79%)
HP:0001385	Hip dysplasia	Frequent (30-79%)
HP:0001396	Cholestasis	Frequent (30-79%)
HP:0001409	Portal hypertension	Frequent (30-79%)
HP:0001540	Diastasis recti	Frequent (30-79%)
HP:0001623	Breech presentation	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002570	Steatorrhea	Frequent (30-79%)
HP:0002611	Cholestatic liver disease	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004840	Hypochromic microcytic anemia	Frequent (30-79%)
HP:0008850	Severe postnatal growth retardation	Frequent (30-79%)
HP:0011400	Abnormal CNS myelination	Frequent (30-79%)
HP:0011998	Postprandial hyperglycemia	Frequent (30-79%)
HP:0012115	Hepatitis	Frequent (30-79%)
HP:0012157	Subcortical cerebral atrophy	Frequent (30-79%)
HP:0100886	Abnormality of globe location	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated sedoheptulokinase deficiency
Mondo ID	MONDO:0014969
OMIM	617213
Orphanet	440713
SNOMED CT	124309005
UMLS	C1291373
MedGen	713680
GARD	0018652
Is cancer (heuristic)	no

Also known as: isolated SHPK deficiency · sedoheptulokinase deficiency · SHPKD

Data availability: 3 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorders of pentose/polyol metabolism › inborn disorder of pentose phosphate metabolism › isolated sedoheptulokinase deficiency

Related subtypes (5): pentosuria, anemia, nonspherocytic hemolytic, due to G6PD deficiency, transaldolase deficiency, ribose-5-P isomerase deficiency, transketolase deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

1 benign/likely benign, 1 uncertain significance, 1 affects

ClinVar	Variant (HGVS)	Gene	Classification	Review
372202	NM_013276.4(SHPK):c.355C>T (p.Arg119Ter)	LOC126862464	Uncertain significance	criteria provided, single submitter
372203	NM_013276.4(SHPK):c.211G>T (p.Glu71Ter)	SHPK	Affects	no assertion criteria provided
1170654	NM_013276.4(SHPK):c.495-19dup	SHPK	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SHPK	Moderate	Autosomal recessive	isolated sedoheptulokinase deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SHPK	Orphanet:440713	Isolated sedoheptulokinase deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SHPK	HGNC:1492	ENSG00000197417	Q9UHJ6	Sedoheptulokinase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SHPK	Sedoheptulokinase	Acts as a modulator of macrophage activation through control of glucose metabolism.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SHPK	Enzyme (other)	yes	2.7.1.14	FGGY_N, ATPase_NBD

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
primordial germ cell in gonad	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SHPK	191	ubiquitous	marker	right lobe of liver, primordial germ cell in gonad, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SHPK	2,140

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SHPK	Q9UHJ6	94.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Pentose phosphate pathway	1	951.7×	0.003	SHPK
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.012	SHPK
Metabolism	1	11.6×	0.086	SHPK

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cellular response to interleukin-13	1	8426.0×	0.001	SHPK
pentose-phosphate shunt, non-oxidative branch	1	2808.7×	0.001	SHPK
pentose-phosphate shunt	1	1532.0×	0.001	SHPK
phosphorylation	1	1296.3×	0.001	SHPK
regulation of macrophage activation	1	1296.3×	0.001	SHPK
cellular response to interleukin-4	1	648.1×	0.002	SHPK
regulation of inflammatory response	1	168.5×	0.008	SHPK
carbohydrate metabolic process	1	135.9×	0.008	SHPK
cellular response to lipopolysaccharide	1	98.0×	0.010	SHPK

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SHPK	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SHPK	2.7.1.14	sedoheptulokinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	SHPK
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SHPK	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.