Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature

Summary

Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature (MONDO:0957495) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature
Mondo ID	MONDO:0957495
OMIM	301110
UMLS	C5829585
MedGen	1840221
GARD	0026853
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › hemolytic-uremic syndrome › hereditary hemolytic uremic syndrome › hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature

Related subtypes (1): atypical hemolytic-uremic syndrome

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

6 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2506572	NM_001011551.3(C1GALT1C1):c.266C>T (p.Thr89Ile)	C1GALT1C1	Pathogenic	criteria provided, single submitter
1675199	NM_001011551.3(C1GALT1C1):c.59C>A (p.Ala20Asp)	C1GALT1C1	Likely pathogenic	criteria provided, single submitter
3376970	NM_001011551.3(C1GALT1C1):c.553G>A (p.Gly185Arg)	C1GALT1C1	Likely pathogenic	criteria provided, single submitter
10792	NM_001011551.3(C1GALT1C1):c.393T>A (p.Asp131Glu)	C1GALT1C1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4292916	NM_001011551.3(C1GALT1C1):c.474G>C (p.Leu158Phe)	C1GALT1C1	Uncertain significance	criteria provided, single submitter
4813462	NM_001011551.3(C1GALT1C1):c.192dup (p.Lys65Ter)	C1GALT1C1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
C1GALT1C1	Limited	X-linked	hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature	2

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
C1GALT1C1	HGNC:24338	ENSG00000171155	Q96EU7	C1GALT1-specific chaperone 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C1GALT1C1	C1GALT1-specific chaperone 1	Probable chaperone required for the generation of 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins.

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)
C1GALT1C1	Enzyme (other)	yes	2.4.1.122	C1GALT1/C1GALT1_chp1

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
calcaneal tendon	1
islet of Langerhans	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C1GALT1C1	134	ubiquitous	marker	islet of Langerhans, calcaneal tendon, rectum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C1GALT1C1	806

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C1GALT1C1	Q96EU7	87.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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 C1GALT1C1 causes TNPS	1	671.8×	0.013	C1GALT1C1
Diseases associated with O-glycosylation of proteins	1	215.5×	0.014	C1GALT1C1
O-linked glycosylation of mucins	1	184.2×	0.014	C1GALT1C1
O-linked glycosylation	1	144.6×	0.014	C1GALT1C1
Diseases of glycosylation	1	131.3×	0.014	C1GALT1C1
Diseases of metabolism	1	80.4×	0.019	C1GALT1C1
Post-translational protein modification	1	19.2×	0.067	C1GALT1C1
Disease	1	13.1×	0.081	C1GALT1C1
Metabolism of proteins	1	12.4×	0.081	C1GALT1C1

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
platelet morphogenesis	1	5617.3×	5e-04	C1GALT1C1
platelet activation	1	267.5×	0.004	C1GALT1C1
protein O-linked glycosylation	1	224.7×	0.004	C1GALT1C1

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
C1GALT1C1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
C1GALT1C1	2.4.1.122	N-acetylgalactosaminide beta-1,3-galactosyltransferase

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	C1GALT1C1
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)
C1GALT1C1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.