Hereditary cryohydrocytosis with reduced stomatin

Summary

Hereditary cryohydrocytosis with reduced stomatin (MONDO:0012143) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 170
• Phenotypes (HPO): 32

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0000518	Cataract	Frequent (30-79%)
HP:0000952	Jaundice	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001433	Hepatosplenomegaly	Frequent (30-79%)
HP:0003575	Increased intracellular sodium	Frequent (30-79%)
HP:0004446	Stomatocytosis	Frequent (30-79%)
HP:0005525	Spontaneous hemolytic crises	Frequent (30-79%)
HP:0008897	Postnatal growth retardation	Frequent (30-79%)
HP:0011972	Hypoglycorrhachia	Frequent (30-79%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0000475	Broad neck	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0001156	Brachydactyly	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001258	Spastic paraplegia	Occasional (5-29%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0001334	Communicating hydrocephalus	Occasional (5-29%)
HP:0002719	Recurrent infections	Occasional (5-29%)
HP:0002908	Conjugated hyperbilirubinemia	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0007229	Intracerebral periventricular calcifications	Occasional (5-29%)
HP:0010306	Short thorax	Occasional (5-29%)
HP:0010920	Zonular cataract	Occasional (5-29%)
HP:0012430	Cerebral white matter hypoplasia	Occasional (5-29%)
HP:0012448	Delayed myelination	Occasional (5-29%)
HP:0012695	Decreased thalamic volume	Occasional (5-29%)
HP:0100022	Abnormality of movement	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary cryohydrocytosis with reduced stomatin
Mondo ID	MONDO:0012143
MeSH	C563840
OMIM	608885
Orphanet	168577
ICD-11	1459095719
UMLS	C1837206
MedGen	332390
GARD	0017036
Is cancer (heuristic)	no

Also known as: ChC type 2 · cryohydrocytosis, stomatin-deficient, with mental retardation, seizures, cataracts, and massive hepatosplenomegaly · hereditary cryohydrocytosis type 2 · sdCHC · SDCHCN · stomatin-deficient cryohydrocytosis

Data availability: 170 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia › familial hemolytic anemia › hereditary cryohydrocytosis with reduced stomatin

Related subtypes (22): congenital nonspherocytic hemolytic anemia, elliptocytosis 2, southeast Asian ovalocytosis, overhydrated hereditary stomatocytosis, cryohydrocytosis, dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, abetalipoproteinemia, hemolytic anemia due to diphosphoglycerate mutase deficiency, glycogen storage disease VII, cutaneous porphyria, familial pseudohyperkalemia, renal tubular acidosis, distal, 4, with hemolytic anemia, elliptocytosis 1, glycogen storage disease due to aldolase A deficiency, primary CD59 deficiency, triosephosphate isomerase deficiency, dehydrated hereditary stomatocytosis 2, Rh deficiency syndrome, hereditary spherocytosis, congenital dyserythropoietic anemia, X-linked congenital hemolytic anemia, hemolytic disease of fetus and newborn, RH-induced

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

170 retrieved; paginated sample, class counts are floors:

61 uncertain significance, 34 likely benign, 25 benign/likely benign, 19 benign, 18 conflicting classifications of pathogenicity, 8 pathogenic, 4 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1189059	NM_006516.4(SLC2A1):c.399C>A (p.Cys133Ter)	SLC2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
16118	NM_006516.4(SLC2A1):c.376C>T (p.Arg126Cys)	SLC2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
198842	NM_006516.4(SLC2A1):c.997C>T (p.Arg333Trp)	SLC2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
207193	NM_006516.4(SLC2A1):c.667C>T (p.Arg223Trp)	SLC2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
207196	NM_006516.4(SLC2A1):c.988C>T (p.Arg330Ter)	SLC2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
207225	NM_006516.4(SLC2A1):c.19-2A>G	SLC2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
218333	NM_006516.4(SLC2A1):c.857G>A (p.Gly286Asp)	SLC2A1	Pathogenic	criteria provided, single submitter
218334	NM_006516.4(SLC2A1):c.1303ATC[1] (p.Ile436del)	SLC2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
619980	NM_006516.4(SLC2A1):c.161dup (p.Ser55fs)	SLC2A1	Pathogenic	criteria provided, single submitter
662199	NM_006516.4(SLC2A1):c.101A>G (p.Asn34Ser)	SLC2A1	Pathogenic	criteria provided, multiple submitters, no conflicts
96708	NM_006516.4(SLC2A1):c.1372C>T (p.Arg458Trp)	SLC2A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973266	NM_006516.4(SLC2A1):c.1028dup (p.Met344fs)	SLC2A1	Pathogenic	criteria provided, single submitter
3376227	NM_006516.4(SLC2A1):c.680-12C>A	SLC2A1	Likely pathogenic	criteria provided, single submitter
1203673	NM_006516.4(SLC2A1):c.1297G>A (p.Val433Ile)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1320581	NM_006516.4(SLC2A1):c.523G>A (p.Gly175Ser)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1447855	NM_006516.4(SLC2A1):c.1260G>A (p.Met420Ile)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1721931	NM_006516.4(SLC2A1):c.1130C>A (p.Ala377Asp)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198195	NM_006516.4(SLC2A1):c.790C>T (p.Arg264Cys)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198843	NM_006516.4(SLC2A1):c.1016T>C (p.Ile339Thr)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207180	NM_006516.4(SLC2A1):c.258C>T (p.Phe86=)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207189	NM_006516.4(SLC2A1):c.313G>A (p.Val105Met)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207217	NM_006516.4(SLC2A1):c.1408G>T (p.Gly470Trp)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207228	NM_006516.4(SLC2A1):c.805C>T (p.Arg269Cys)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2108956	NM_006516.4(SLC2A1):c.275G>A (p.Arg92Gln)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
212203	NM_006516.4(SLC2A1):c.1395C>T (p.Ser465=)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
406880	NM_006516.4(SLC2A1):c.188C>T (p.Thr63Met)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
516467	NM_006516.4(SLC2A1):c.903G>A (p.Ala301=)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
594894	NM_006516.4(SLC2A1):c.322G>A (p.Val108Met)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
626018	NM_006516.4(SLC2A1):c.192C>G (p.Leu64=)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
656374	NM_006516.4(SLC2A1):c.26C>T (p.Thr9Met)	SLC2A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 7 · 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
SLC2A1	Supportive	Autosomal dominant	hereditary cryohydrocytosis with reduced stomatin	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC2A1	Orphanet:168577	Hereditary cryohydrocytosis with reduced stomatin
SLC2A1	Orphanet:1942	Epilepsy with myoclonic-atonic seizures
SLC2A1	Orphanet:2131	Alternating hemiplegia of childhood
SLC2A1	Orphanet:53583	Paroxysmal dystonic choreathetosis with episodic ataxia and spasticity
SLC2A1	Orphanet:71277	Classic glucose transporter type 1 deficiency syndrome
SLC2A1	Orphanet:86911	Epilepsy with myoclonic absences
SLC2A1	Orphanet:98811	Paroxysmal exertion-induced dyskinesia

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
SLC2A1	HGNC:11005	ENSG00000117394	P11166	Solute carrier family 2, facilitated glucose transporter member 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC2A1	Solute carrier family 2, facilitated glucose transporter member 1	Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC2A1	Transporter	yes		Glu_transpt_1, Sugar/inositol_transpt, MFS_sugar_transport-like

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
skin of abdomen	1
sural nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC2A1	250	ubiquitous	marker	tibial nerve, sural nerve, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC2A1	5,711

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC2A1	P11166	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1)	1	11420.0×	4e-04	SLC2A1
Lactose synthesis	1	3806.7×	7e-04	SLC2A1
Vitamin C (ascorbate) metabolism	1	1427.5×	0.001	SLC2A1
Cellular hexose transport	1	543.8×	0.002	SLC2A1
Regulation of insulin secretion	1	219.6×	0.005	SLC2A1

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
response to Thyroglobulin triiodothyronine	1	5617.3×	0.002	SLC2A1
long-chain fatty acid import across plasma membrane	1	4213.0×	0.002	SLC2A1
GDP-L-fucose salvage	1	4213.0×	0.002	SLC2A1
D-glucose import across plasma membrane	1	2808.7×	0.002	SLC2A1
L-ascorbic acid metabolic process	1	1532.0×	0.002	SLC2A1
dehydroascorbic acid transport	1	1203.7×	0.002	SLC2A1
cellular hyperosmotic response	1	1203.7×	0.002	SLC2A1
D-glucose transmembrane transport	1	936.2×	0.003	SLC2A1
obsolete D-glucose import	1	842.6×	0.003	SLC2A1
photoreceptor cell maintenance	1	358.6×	0.005	SLC2A1
cellular response to glucose starvation	1	337.0×	0.005	SLC2A1
response to insulin	1	230.8×	0.006	SLC2A1
cellular response to mechanical stimulus	1	216.1×	0.006	SLC2A1
female pregnancy	1	210.7×	0.006	SLC2A1
cerebral cortex development	1	205.5×	0.006	SLC2A1
transport across blood-brain barrier	1	179.3×	0.007	SLC2A1
central nervous system development	1	115.4×	0.009	SLC2A1
protein-containing complex assembly	1	113.9×	0.009	SLC2A1
response to hypoxia	1	95.8×	0.010	SLC2A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SLC2A1	EMETINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC2A1	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EMETINE	4	SLC2A1
GOSSYPOL	3	SLC2A1
CYCLOHEXIMIDE	2	SLC2A1
GENISTEIN	2	SLC2A1
COLFORSIN	2	SLC2A1
KAEMPFEROL	1	SLC2A1
PD-0166285	1	SLC2A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SLC2A1	158	Binding:130, ADMET:24, Functional:4

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SLC2A1	158

Pharmacogenomics

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

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

Chemical tractability of cohort targets

7 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.

Compound	Max phase	Cohort target (bioactivity)
EMETINE	4	SLC2A1
GOSSYPOL	3	SLC2A1
CYCLOHEXIMIDE	2	SLC2A1
GENISTEIN	2	SLC2A1
COLFORSIN	2	SLC2A1
KAEMPFEROL	1	SLC2A1
PD-0166285	1	SLC2A1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SLC2A1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.