8p23.1 duplication syndrome

Summary

8p23.1 duplication syndrome (MONDO:0016659) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 18

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.72	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0002463	Language impairment	Frequent (30-79%)
HP:0002553	Highly arched eyebrow	Frequent (30-79%)
HP:0030680	Abnormal cardiovascular system morphology	Frequent (30-79%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000445	Wide nose	Occasional (5-29%)
HP:0000490	Deeply set eye	Occasional (5-29%)
HP:0000846	Adrenal insufficiency	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001636	Tetralogy of Fallot	Occasional (5-29%)
HP:0001642	Pulmonic stenosis	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0012471	Thick vermilion border	Occasional (5-29%)
HP:0100777	Exostoses	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	8p23.1 duplication syndrome
Mondo ID	MONDO:0016659
Orphanet	251076
SNOMED CT	765140006
UMLS	C4707330
MedGen	1645138
GARD	0010304
Is cancer (heuristic)	no

Also known as: dup(8)(p23.1p23.1) · trisomy 8p23.1

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal duplication › partial duplication of chromosome 8 › partial duplication of the short arm of chromosome 8 › 8p23.1 duplication syndrome

Related subtypes (1): trisomy 8p

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 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2580324	GRCh37/hg19 8p23.1(chr8:7080281-12045269)x3	BLK	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY

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
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom

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
lymph node	1
male germ line stem cell (sensu Vertebrata) in testis	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BLK	2,967

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BLK	P51451	81.89

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
RUNX1 regulates transcription of genes involved in BCR signaling	1	1903.3×	0.005	BLK
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.009	BLK
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.009	BLK
Transcriptional regulation by RUNX1	1	146.4×	0.015	BLK
Adaptive Immune System	1	29.8×	0.060	BLK
RNA Polymerase II Transcription	1	22.5×	0.067	BLK
Gene expression (Transcription)	1	17.8×	0.072	BLK
Generic Transcription Pathway	1	15.1×	0.074	BLK
Immune System	1	13.0×	0.077	BLK

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
peptidyl-tyrosine phosphorylation	1	421.3×	0.007	BLK
B cell receptor signaling pathway	1	401.2×	0.007	BLK
positive regulation of insulin secretion	1	255.3×	0.008	BLK
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.009	BLK
intracellular signal transduction	1	38.1×	0.031	BLK
cell differentiation	1	29.1×	0.034	BLK

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
BLK	AFATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BLK	62	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AFATINIB	4	BLK
FEDRATINIB	4	BLK
AXITINIB	4	BLK
SORAFENIB	4	BLK
NERATINIB	4	BLK
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK
NINTEDANIB	4	BLK
SUNITINIB	4	BLK
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
MASITINIB	3	BLK
LINIFANIB	3	BLK
CANERTINIB	3	BLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BLK	483	Binding:477, ADMET:4, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BLK	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BLK	483

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

30 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)
AFATINIB	4	BLK
FEDRATINIB	4	BLK
AXITINIB	4	BLK
SORAFENIB	4	BLK
NERATINIB	4	BLK
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK
NINTEDANIB	4	BLK
SUNITINIB	4	BLK
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
MASITINIB	3	BLK
LINIFANIB	3	BLK
CANERTINIB	3	BLK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BLK
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.