van den Ende-Gupta syndrome

Summary

van den Ende-Gupta syndrome (MONDO:0010959) is a disease caused by SCARF2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SCARF2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 30
• Phenotypes (HPO): 38

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		29	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

38 HPO clinical features (Orphanet curated; top 38 by frequency):

HPO ID	Term	Frequency
HP:0000232	Everted lower lip vermilion	Very frequent (80-99%)
HP:0000272	Malar flattening	Very frequent (80-99%)
HP:0000581	Blepharophimosis	Very frequent (80-99%)
HP:0001166	Arachnodactyly	Very frequent (80-99%)
HP:0012385	Camptodactyly	Very frequent (80-99%)
HP:0001833	Long foot	Frequent (30-79%)
HP:0003083	Dislocated radial head	Frequent (30-79%)
HP:0004691	2-3 toe syndactyly	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0006236	Slender metacarpals	Frequent (30-79%)
HP:0006487	Bowing of the long bones	Frequent (30-79%)
HP:0034391	Elbow contracture	Frequent (30-79%)
HP:0034392	Joint contracture	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000324	Facial asymmetry	Frequent (30-79%)
HP:0000325	Triangular face	Frequent (30-79%)
HP:0000411	Protruding ear	Frequent (30-79%)
HP:0000460	Narrow nose	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000883	Thin ribs	Frequent (30-79%)
HP:0000895	Lateral clavicle hook	Frequent (30-79%)
HP:0001822	Hallux valgus	Frequent (30-79%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000430	Underdeveloped nasal alae	Occasional (5-29%)
HP:0000647	Sclerocornea	Occasional (5-29%)
HP:0000678	Dental crowding	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0001363	Craniosynostosis	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0004411	Deviated nasal septum	Occasional (5-29%)
HP:0006633	Glenoid fossa hypoplasia	Occasional (5-29%)
HP:0008744	Abnormal aryepiglottic fold morphology	Occasional (5-29%)
HP:0009929	Abnormal columella morphology	Occasional (5-29%)
HP:0030084	Clinodactyly	Occasional (5-29%)
HP:0034671	Knee contracture	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	van den Ende-Gupta syndrome
Mondo ID	MONDO:0010959
MeSH	C535909
OMIM	600920
Orphanet	2460
DOID	DOID:0111699
ICD-11	1740735985
SNOMED CT	719845008
UMLS	C1833136
MedGen	322127
GARD	0003382
Is cancer (heuristic)	no

Also known as: Marden Walker like syndrome · Marden Walker like syndrome without psychomotor retardation · Marden-Walker-like syndrome · Van den Ende Gupta syndrome · van den Ende-Gupta syndrome · VDEGS

Data availability: 30 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › multiple congenital anomalies/dysmorphic syndrome › multiple congenital anomalies/dysmorphic syndrome without intellectual disability › van den Ende-Gupta syndrome

Related subtypes (167): Treacher-Collins syndrome, branchio-oto-renal syndrome, acrorenal syndrome, Townes-Brocks syndrome, Ascher syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, branchiooculofacial syndrome, Gordon syndrome, cataract-aberrant oral frenula-growth delay syndrome, cherubism, Alagille syndrome, cleft palate-lateral synechia syndrome, blepharocheilodontic syndrome, craniofacial-deafness-hand syndrome, cryptomicrotia-brachydactyly-excess fingertip arch syndrome, Beare-Stevenson cutis gyrata syndrome, Cyprus facial-neuromusculoskeletal syndrome, deafness-craniofacial syndrome, short stature-valvular heart disease-characteristic facies syndrome, 3-M syndrome, external auditory canal atresia-vertical talus-hypertelorism syndrome, femoral-facial syndrome, multinodular goiter-cystic kidney-polydactyly syndrome, hand-foot-genital syndrome, Bencze syndrome, oculoauriculovertebral spectrum with radial defects, Holt-Oram syndrome, mullerian duct anomalies-limb anomalies syndrome, Aase-Smith syndrome, LADD syndrome, Noonan syndrome with multiple lentigines, median nodule of the upper lip, Nager acrofacial dysostosis, Marshall syndrome, Binder syndrome, Schilbach-Rott syndrome, nasopalpebral lipoma-coloboma syndrome, autosomal dominant prognathism, short stature-craniofacial anomalies-genital hypoplasia syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, scalp-ear-nipple syndrome, flat face-microstomia-ear anomaly syndrome, Czeizel-Losonci syndrome, otospondylomegaepiphyseal dysplasia, autosomal dominant, ventricular extrasystoles with syncopal episodes-perodactyly-robin sequence syndrome, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, acrofacial dysostosis, Weyers type, Freeman-Sheldon syndrome, Ackerman syndrome, acro-renal-mandibular syndrome, acrocraniofacial dysostosis, PAGOD syndrome, alar cartilages hypoplasia-coloboma-telecanthus syndrome, microcephaly-albinism-digital anomalies syndrome, fetal akinesia deformation sequence, Cooper-Jabs syndrome, Barber-Say syndrome, Beemer-Ertbruggen syndrome, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, camptodactyly syndrome, Guadalajara type 1, camptodactyly syndrome, Guadalajara type 2, heart defects-limb shortening syndrome, Verloove Vanhorick-Brubakk syndrome, Juberg-Hayward syndrome, heart defect - tongue hamartoma - polysyndactyly syndrome, Fraser syndrome, split hand-foot malformation 1 with sensorineural hearing loss, von Voss-Cherstvoy syndrome, autosomal recessive faciodigitogenital syndrome, gingival fibromatosis-facial dysmorphism syndrome, Fibulo-ulnar hypoplasia-renal anomalies syndrome, frontofacionasal dysplasia, genito-palato-cardiac syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Holzgreve-Wagner-Rehder syndrome, hydrocephaly-tall stature-joint laxity syndrome, McKusick-Kaufman syndrome, acrofrontofacionasal dysostosis 2, Vici syndrome, Donohue syndrome, Dahlberg-Borer-Newcomer syndrome, macrosomia-microphthalmia-cleft palate syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, Nijmegen breakage syndrome, lethal congenital contracture syndrome 1, Richieri Costa-da Silva syndrome, Keipert syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, ichthyosis-oral and digital anomalies syndrome, otoonychoperoneal syndrome, PHAVER syndrome, polysyndactyly-cardiac malformation syndrome, postaxial acrofacial dysostosis, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, renal-genital-middle ear anomalies, Richieri Costa-Pereira syndrome, SHORT syndrome, tetraamelia-multiple malformations syndrome, thymic-renal-anal-lung dysplasia, trigonocephaly-bifid nose-acral anomalies syndrome, white forelock with malformations, syndactyly-telecanthus-anogenital and renal malformations syndrome, Abruzzo-Erickson syndrome, CHILD syndrome, pentalogy of Cantrell, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, short tarsus-absence of lower eyelashes syndrome, PARC syndrome, CODAS syndrome, pectus excavatum-macrocephaly-dysplastic nails syndrome, velo-facial-skeletal syndrome, anophthalmia plus syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, diaphragmatic defect-limb deficiency-skull defect syndrome, cleft lip/palate-intestinal malrotation-cardiopathy syndrome, Matthew-Wood syndrome, microcephaly-cardiac defect-lung malsegmentation syndrome, dislocation of the hip-dysmorphism syndrome, short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome, grange syndrome, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, arhinia, choanal atresia, and microphthalmia, anonychia-microcephaly syndrome, developmental malformations-deafness-dystonia syndrome, lethal congenital contracture syndrome 2, craniolenticulosutural dysplasia, 8q22.1 microdeletion syndrome, Braddock syndrome, choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome, BNAR syndrome, Frias syndrome, lethal congenital contracture syndrome 3, Fontaine progeroid syndrome, microcephaly-facio-cardio-skeletal syndrome, Hadziselimovic type, Nijmegen breakage syndrome-like disorder, Warsaw breakage syndrome, even-plus syndrome, split-foot malformation-mesoaxial polydactyly syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, digitotalar dysmorphism, heart-hand syndrome type 2, night blindness-skeletal anomalies-dysmorphism syndrome, Charlie M syndrome, facial dysmorphism-anorexia-cachexia-eye and skin anomalies syndrome, cleft lip-retinopathy syndrome, Cole-Carpenter syndrome, progressive non-infectious anterior vertebral fusion, dysmorphism-pectus carinatum-joint laxity syndrome, Hirschsprung disease-type D brachydactyly syndrome, mandibuloacral dysplasia, contractures - webbed neck - micrognathia - hypoplastic nipples syndrome, Thomas syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, branchiootic syndrome, auricular abnormalities-cleft lip with or without cleft palate-ocular abnormalities syndrome, Axenfeld-Rieger syndrome, macrostomia-preauricular tags-external ophthalmoplegia syndrome, pelvis syndrome, Fanconi anemia, van der Woude syndrome, hypertrichosis-acromegaloid facial appearance syndrome, 49,XYYYY syndrome, congenital vertebral-cardiac-renal anomalies syndrome, structural heart defects and renal anomalies syndrome, Greig cephalopolysyndactyly-contiguous gene 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

30 retrieved; paginated sample, class counts are floors:

8 pathogenic, 8 benign, 6 likely pathogenic, 5 uncertain significance, 2 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184854	NM_182895.5(SCARF2):c.651C>G (p.Cys217Trp)	SCARF2	Pathogenic	no assertion criteria provided
1184855	NM_182895.5(SCARF2):c.466TGCCAG[1] (p.156CQ[1])	SCARF2	Pathogenic	no assertion criteria provided
144050	NM_182895.5(SCARF2):c.190T>C (p.Cys64Arg)	SCARF2	Pathogenic	no assertion criteria provided
144051	NM_182895.5(SCARF2):c.2531del (p.Gln844fs)	SCARF2	Pathogenic	no assertion criteria provided
1526095	NM_182895.5(SCARF2):c.1104C>A (p.Tyr368Ter)	SCARF2	Pathogenic	criteria provided, single submitter
1697232	NM_182895.5(SCARF2):c.220G>T (p.Glu74Ter)	SCARF2	Pathogenic	no assertion criteria provided
190239	NM_182895.5(SCARF2):c.441_457del (p.Trp148fs)	SCARF2	Pathogenic	no assertion criteria provided
31047	NM_182895.5(SCARF2):c.1328_1329del (p.Val443fs)	SCARF2	Pathogenic	criteria provided, single submitter
2500262	NM_182895.5(SCARF2):c.3G>A (p.Met1Ile)	SCARF2	Likely pathogenic	criteria provided, single submitter
31046	NM_182895.5(SCARF2):c.773G>A (p.Cys258Tyr)	SCARF2	Likely pathogenic	criteria provided, single submitter
4533365	NM_182895.5(SCARF2):c.15del (p.Arg7fs)	SCARF2	Likely pathogenic	criteria provided, single submitter
4845895	NM_182895.5(SCARF2):c.2227_2238delinsAGGCGGGGCCGCA (p.Ala743fs)	SCARF2	Likely pathogenic	criteria provided, single submitter
803645	NM_182895.5(SCARF2):c.915C>G (p.Cys305Trp)	SCARF2	Likely pathogenic	criteria provided, single submitter
993021	NM_182895.5(SCARF2):c.25del (p.Ala9fs)	SCARF2	Likely pathogenic	no assertion criteria provided
1029235	NM_182895.5(SCARF2):c.1907C>T (p.Ala636Val)	SCARF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029236	NM_182895.5(SCARF2):c.1978G>T (p.Ala660Ser)	SCARF2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029234	NM_182895.5(SCARF2):c.1822A>T (p.Ser608Cys)	SCARF2	Uncertain significance	criteria provided, single submitter
1323554	NM_182895.5(SCARF2):c.1425-11dup	SCARF2	Uncertain significance	criteria provided, single submitter
3068052	NM_182895.5(SCARF2):c.649T>C (p.Cys217Arg)	SCARF2	Uncertain significance	criteria provided, single submitter
3780580	NM_182895.5(SCARF2):c.2230_2231insA (p.Arg744fs)	SCARF2	Uncertain significance	criteria provided, single submitter
4079957	NM_182895.5(SCARF2):c.29_60del (p.Gly10fs)	SCARF2	Uncertain significance	criteria provided, single submitter
1332919	NM_182895.5(SCARF2):c.2287dup (p.Ala763fs)	SCARF2	Benign	criteria provided, single submitter
1332920	NM_182895.5(SCARF2):c.2236dup (p.Arg746fs)	SCARF2	Benign	criteria provided, single submitter
1332921	NM_182895.5(SCARF2):c.2248dup (p.Leu750fs)	SCARF2	Benign	criteria provided, single submitter
1332922	NM_182895.5(SCARF2):c.2247C>G (p.Gly749=)	SCARF2	Benign	criteria provided, single submitter
1332923	NM_182895.5(SCARF2):c.2187G>C (p.Glu729Asp)	SCARF2	Benign	criteria provided, single submitter
1332924	NM_182895.5(SCARF2):c.2181C>G (p.Pro727=)	SCARF2	Benign	criteria provided, single submitter
518324	NM_182895.5(SCARF2):c.2498C>G (p.Ala833Gly)	SCARF2	Benign	criteria provided, multiple submitters, no conflicts
518325	NM_182895.5(SCARF2):c.2444C>G (p.Ala815Gly)	SCARF2	Benign	criteria provided, multiple submitters, no conflicts
522182	NM_182895.5(SCARF2):c.1967C>T (p.Pro656Leu)	SCARF2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SCARF2	Definitive	Autosomal recessive	van den Ende-Gupta syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCARF2	Orphanet:2460	Van den Ende-Gupta syndrome

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
SCARF2	HGNC:19869	ENSG00000244486	Q96GP6	Scavenger receptor class F member 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCARF2	Scavenger receptor class F member 2	Probable adhesion protein, which mediates homophilic and heterophilic interactions.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCARF2	Other/Unknown	no		EGF, LE_dom, Growth_fac_rcpt_cys_sf

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
ascending aorta	1
right coronary artery	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCARF2	165	ubiquitous	marker	right coronary artery, ascending aorta, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCARF2	778

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SCARF2	Q96GP6	64.63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
heterophilic cell-cell adhesion	1	337.0×	0.003	SCARF2

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
SCARF2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	1	SCARF2

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)
SCARF2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.