Chromosome 6pter-p24 deletion syndrome

Summary

Chromosome 6pter-p24 deletion syndrome (MONDO:0012948) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 39

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		35	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

39 HPO clinical features (Orphanet curated; top 39 by frequency):

HPO ID	Term	Frequency
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000369	Low-set ears	Very frequent (80-99%)
HP:0000593	Abnormal anterior chamber morphology	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001256	Intellectual disability, mild	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0000164	Abnormality of the dentition	Frequent (30-79%)
HP:0000272	Malar flattening	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000319	Smooth philtrum	Frequent (30-79%)
HP:0000322	Short philtrum	Frequent (30-79%)
HP:0000337	Broad forehead	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000430	Underdeveloped nasal alae	Frequent (30-79%)
HP:0000445	Wide nose	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000501	Glaucoma	Frequent (30-79%)
HP:0000627	Posterior embryotoxon	Frequent (30-79%)
HP:0001631	Atrial septal defect	Frequent (30-79%)
HP:0002714	Downturned corners of mouth	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0007676	Hypoplasia of the iris	Frequent (30-79%)
HP:0007957	Corneal opacity	Frequent (30-79%)
HP:0008499	High hypermetropia	Frequent (30-79%)
HP:0011483	Anterior synechiae of the anterior chamber	Frequent (30-79%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0001773	Short foot	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0003422	Vertebral segmentation defect	Occasional (5-29%)
HP:0004279	Short palm	Occasional (5-29%)
HP:0005930	Abnormality of epiphysis morphology	Occasional (5-29%)
HP:0009918	Ectopia pupillae	Occasional (5-29%)
HP:0100716	Self-injurious behavior	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 6pter-p24 deletion syndrome
Mondo ID	MONDO:0012948
MeSH	C567239
OMIM	612582
Orphanet	96125
DOID	DOID:0060422
SNOMED CT	718688008
UMLS	C2675486
MedGen	393396
GARD	0016845
Is cancer (heuristic)	no

Also known as: 6p subtelomeric deletion syndrome · 6p25 microdeletion syndrome · chromosome 6pter-p24 deletion syndrome · chromosome 6pter-p24 deletion syndrome, isolated cases · distal deletion 6p · distal monosomy type 6p · monosomy 6p25

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › anterior segment dysgenesis › iridogoniodysgenesis › chromosome 6pter-p24 deletion syndrome

Related subtypes (6): congenital microcoria, aniridia-cerebellar ataxia-intellectual disability syndrome, bilateral acute depigmentation of the iris, Rieger anomaly, congenital ectropion uveae, FOXC1-related anterior segment dysgenesis

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

1 retrieved; paginated sample, class counts are floors:

1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
4279952	GRCh37/hg19 6p25.3-25.1(chr6:154749-5886174)x1	BPHL	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
BPHL	HGNC:1094	ENSG00000137274	Q86WA6	Serine hydrolase BPHL	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BPHL	Serine hydrolase BPHL	Specific alpha-amino acid ester serine hydrolase that prefers small, hydrophobic, and aromatic side chains and does not have a stringent requirement for the leaving group other than preferring a primary alcohol.

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)
BPHL	Other/Unknown	no		AB_hydrolase_1, AB_hydrolase_fold

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
adult mammalian kidney	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BPHL	253	ubiquitous	marker	right lobe of liver, adult mammalian kidney, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BPHL	1,390

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BPHL	Q86WA6	4

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
Phase I - Functionalization of compounds	1	219.6×	0.012	BPHL
Biological oxidations	1	129.8×	0.012	BPHL
Metabolism	1	11.6×	0.086	BPHL

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
homocysteine metabolic process	1	1872.4×	0.002	BPHL
amino acid metabolic process	1	802.5×	0.002	BPHL
response to toxic substance	1	210.7×	0.006	BPHL
xenobiotic metabolic process	1	149.1×	0.007	BPHL

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BPHL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
BPHL	4	Binding:4

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	BPHL

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)
BPHL	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.