MEND syndrome

Summary

MEND syndrome (MONDO:0010498) is a disease caused by EBP (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: EBP (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 25
• Phenotypes (HPO): 45

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		24	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

45 HPO clinical features (Orphanet curated; top 45 by frequency):

HPO ID	Term	Frequency
HP:0003462	Elevated 8-dehydrocholesterol	Very frequent (80-99%)
HP:0003465	Elevated 8(9)-cholestenol	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000238	Hydrocephalus	Frequent (30-79%)
HP:0000260	Wide anterior fontanel	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000422	Abnormality of the nasal bridge	Frequent (30-79%)
HP:0000426	Prominent nasal bridge	Frequent (30-79%)
HP:0000472	Long neck	Frequent (30-79%)
HP:0000474	Thickened nuchal skin fold	Frequent (30-79%)
HP:0000506	Telecanthus	Frequent (30-79%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0000568	Microphthalmia	Frequent (30-79%)
HP:0000582	Upslanted palpebral fissure	Frequent (30-79%)
HP:0000960	Sacral dimple	Frequent (30-79%)
HP:0001161	Hand polydactyly	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:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001305	Dandy-Walker malformation	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001650	Aortic valve stenosis	Frequent (30-79%)
HP:0001845	Overlapping toe	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002509	Limb hypertonia	Frequent (30-79%)
HP:0002808	Kyphosis	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004691	2-3 toe syndactyly	Frequent (30-79%)
HP:0005590	Spotty hypopigmentation	Frequent (30-79%)
HP:0006958	Abnormal auditory evoked potentials	Frequent (30-79%)
HP:0008064	Ichthyosis	Frequent (30-79%)
HP:0009941	Asymmetry of the mouth	Frequent (30-79%)
HP:0010055	Broad hallux	Frequent (30-79%)
HP:0010557	Overlapping fingers	Frequent (30-79%)
HP:0011800	Midface retrusion	Frequent (30-79%)
HP:0012433	Abnormal social behavior	Frequent (30-79%)
HP:0100807	Long fingers	Frequent (30-79%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000752	Hyperactivity	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	MEND syndrome
Mondo ID	MONDO:0010498
OMIM	300960
Orphanet	401973
DOID	DOID:0111865
UMLS	C4085243
MedGen	905986
GARD	0017666
Is cancer (heuristic)	no

Also known as: Male EBP disorder with neurological defects · MEND · MEND syndrome · MEND syndrome, X-linked recessive

Data availability: 25 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › sterol biosynthesis disorder › MEND syndrome

Related subtypes (6): Greenberg dysplasia, X-linked chondrodysplasia punctata, CHILD syndrome, microcephaly-congenital cataract-psoriasiform dermatitis syndrome, mevalonate kinase deficiency, cholesterol biosynthetic process disease

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

25 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 6 conflicting classifications of pathogenicity, 4 pathogenic, 2 benign/likely benign, 1 benign, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11492	NM_006579.3(EBP):c.440G>A (p.Arg147His)	EBP	Pathogenic	criteria provided, multiple submitters, no conflicts
11493	NM_006579.3(EBP):c.53T>C (p.Leu18Pro)	EBP	Pathogenic	no assertion criteria provided
158530	NM_006579.3(EBP):c.141G>T (p.Trp47Cys)	EBP	Pathogenic	criteria provided, single submitter
209040	NM_006579.3(EBP):c.139T>C (p.Trp47Arg)	EBP	Pathogenic	no assertion criteria provided
265110	NM_006579.3(EBP):c.439C>T (p.Arg147Cys)	EBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
209039	NM_006579.3(EBP):c.224T>A (p.Ile75Asn)	EBP	Likely pathogenic	criteria provided, single submitter
158551	NM_006579.3(EBP):c.511C>T (p.Arg171Cys)	EBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2664912	NM_006579.3(EBP):c.424C>T (p.Arg142Cys)	EBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3086881	NM_006579.3(EBP):c.250G>A (p.Val84Ile)	EBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3598326	NM_006579.3(EBP):c.27C>G (p.His9Gln)	EBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
759959	NM_006579.3(EBP):c.414C>T (p.Ile138=)	EBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
811902	NM_006579.3(EBP):c.188G>A (p.Arg63Gln)	EBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1299857	NM_006579.3(EBP):c.175G>A (p.Gly59Arg)	EBP	Uncertain significance	criteria provided, single submitter
1330409	NM_006579.3(EBP):c.283G>A (p.Ala95Thr)	EBP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1526120	NM_006579.3(EBP):c.556T>C (p.Trp186Arg)	EBP	Uncertain significance	criteria provided, multiple submitters, no conflicts
3013142	NM_006579.3(EBP):c.185G>A (p.Arg62Gln)	EBP	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598325	NM_006579.3(EBP):c.25C>T (p.His9Tyr)	EBP	Uncertain significance	criteria provided, single submitter
3598328	NM_006579.3(EBP):c.50G>C (p.Arg17Thr)	EBP	Uncertain significance	criteria provided, single submitter
3598329	NM_006579.3(EBP):c.193T>C (p.Ser65Pro)	EBP	Uncertain significance	criteria provided, single submitter
3598330	NM_006579.3(EBP):c.347A>G (p.Asn116Ser)	EBP	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598331	NM_006579.3(EBP):c.604G>C (p.Val202Leu)	EBP	Uncertain significance	criteria provided, single submitter
3598332	NM_006579.3(EBP):c.626A>C (p.Lys209Thr)	EBP	Uncertain significance	criteria provided, single submitter
158531	NM_006579.3(EBP):c.15G>T (p.Ala5=)	EBP	Benign	criteria provided, multiple submitters, no conflicts
218685	NM_006579.3(EBP):c.13G>A (p.Ala5Thr)	EBP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
592979	NM_006579.3(EBP):c.650C>T (p.Thr217Met)	EBP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 32 · Orphanet: 6 · 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
EBP	Strong	X-linked	MEND syndrome	9
GLB1	Strong	X-linked	MEND syndrome	23

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EBP	Orphanet:35173	X-linked dominant chondrodysplasia punctata
EBP	Orphanet:401973	MEND syndrome
GLB1	Orphanet:309310	Mucopolysaccharidosis type 4B
GLB1	Orphanet:79255	GM1 gangliosidosis type 1
GLB1	Orphanet:79256	GM1 gangliosidosis type 2
GLB1	Orphanet:79257	GM1 gangliosidosis type 3

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EBP	HGNC:3133	ENSG00000147155	Q15125	3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase	gencc,clinvar
GLB1	HGNC:4298	ENSG00000170266	P16278	Beta-galactosidase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EBP	3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase	Isomerase that catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers a catalytic step in the postlanosterol biosynthesis of cholesterol.
GLB1	Beta-galactosidase	Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EBP	Enzyme (other)	yes	5.3.3.5	EBP, EXPERA
GLB1	Other/Unknown	no		Glycoside_Hdrlase_35, Galactose-bd-like_sf, GH_hydrolase_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right adrenal gland	1
right adrenal gland cortex	1
right lobe of liver	1
monocyte	1
mononuclear cell	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EBP	288	ubiquitous	marker	right lobe of liver, right adrenal gland, right adrenal gland cortex
GLB1	258	ubiquitous	marker	monocyte, mononuclear cell, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EBP	1,684
GLB1	1,578

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GLB1	P16278	8
EBP	Q15125	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MPS IV - Morquio syndrome B (Keratin metabolism)	1	2855.0×	0.006	GLB1
MPS IV - Morquio syndrome B (CS/DS degradation)	1	2855.0×	0.006	GLB1
Defective NEU1 causes sialidosis	1	1427.5×	0.006	GLB1
Cholesterol biosynthesis from zymosterol (modified Kandutsch-Russell pathway)	1	1427.5×	0.006	EBP
Mucopolysaccharidoses	1	951.7×	0.007	GLB1
Cholesterol biosynthesis via desmosterol (Bloch pathway)	1	571.0×	0.009	EBP
Diseases of carbohydrate metabolism	1	407.9×	0.010	GLB1
Keratan sulfate degradation	1	356.9×	0.010	GLB1
Diseases associated with N-glycosylation of proteins	1	317.2×	0.010	GLB1
Heparan sulfate/heparin (HS-GAG) metabolism	1	271.9×	0.010	GLB1
CS/DS degradation	1	271.9×	0.010	GLB1
Keratan sulfate/keratin metabolism	1	248.3×	0.010	GLB1
HS-GAG degradation	1	248.3×	0.010	GLB1
Sialic acid metabolism	1	163.1×	0.013	GLB1
Glycosphingolipid metabolism	1	150.3×	0.013	GLB1
Synthesis of substrates in N-glycan biosythesis	1	146.4×	0.013	GLB1
Glycosphingolipid catabolism	1	146.4×	0.013	GLB1
Glycosaminoglycan metabolism	1	109.8×	0.016	GLB1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	103.8×	0.016	GLB1
Sphingolipid metabolism	1	84.0×	0.019	GLB1
Diseases of glycosylation	1	65.6×	0.023	GLB1
Metabolism of carbohydrates and carbohydrate derivatives	1	60.1×	0.024	GLB1
Diseases of metabolism	1	40.2×	0.034	GLB1
Asparagine N-linked glycosylation	1	30.1×	0.044	GLB1
Metabolism of lipids	1	15.8×	0.080	GLB1
Innate Immune System	1	12.8×	0.095	GLB1
Neutrophil degranulation	1	11.5×	0.101	GLB1
Post-translational protein modification	1	9.6×	0.116	GLB1
Disease	1	6.5×	0.158	GLB1
Immune System	1	6.5×	0.158	GLB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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 cortisone	1	4213.0×	0.002	GLB1
keratan sulfate proteoglycan catabolic process	1	2808.7×	0.002	GLB1
response to Thyroglobulin triiodothyronine	1	2808.7×	0.002	GLB1
obsolete cholesterol biosynthetic process via desmosterol	1	2106.5×	0.002	EBP
galactose catabolic process	1	1404.3×	0.002	GLB1
obsolete cholesterol biosynthetic process via lathosterol	1	1053.2×	0.002	EBP
ganglioside catabolic process	1	936.2×	0.002	GLB1
ossification involved in bone maturation	1	702.2×	0.002	EBP
glycoprotein catabolic process	1	526.6×	0.003	GLB1
cholesterol biosynthetic process	1	210.7×	0.006	EBP
hemopoiesis	1	133.8×	0.009	EBP
cholesterol metabolic process	1	98.0×	0.011	EBP
carbohydrate metabolic process	1	68.0×	0.015	GLB1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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
EBP	TRIFLUPERIDOL
GLB1	MIGALASTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EBP	16	4
GLB1	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRIFLUPERIDOL	4	EBP
TRIPARANOL	4	EBP
BUFLOMEDIL	4	EBP
TRIFLUOPERAZINE	4	EBP
HALOPERIDOL	4	EBP
NAFTIFINE	4	EBP
AMIODARONE	4	EBP
RALOXIFENE	4	EBP
TAMOXIFEN	4	EBP
DOXORUBICIN	4	EBP
MIGALASTAT	4	GLB1
OPIPRAMOL	3	EBP
ENCLOMIPHENE	3	EBP
ZUCLOMIPHENE	2	EBP
LEVEMOPAMIL	2	EBP
NAFOXIDINE	2	EBP
RONIPAMIL	2	EBP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GLB1	124	Binding:123, ADMET:1
EBP	57	Binding:34, Functional:23

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EBP	5.3.3.5	cholestenol DELTA-isomerase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GLB1	124

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

17 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)
TRIFLUPERIDOL	4	EBP
TRIPARANOL	4	EBP
BUFLOMEDIL	4	EBP
TRIFLUOPERAZINE	4	EBP
HALOPERIDOL	4	EBP
NAFTIFINE	4	EBP
AMIODARONE	4	EBP
RALOXIFENE	4	EBP
TAMOXIFEN	4	EBP
DOXORUBICIN	4	EBP
MIGALASTAT	4	GLB1
OPIPRAMOL	3	EBP
ENCLOMIPHENE	3	EBP
ZUCLOMIPHENE	2	EBP
LEVEMOPAMIL	2	EBP
NAFOXIDINE	2	EBP
RONIPAMIL	2	EBP

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	EBP, GLB1
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.