Intellectual developmental disorder with dysmorphic facies and ptosis

Summary

Intellectual developmental disorder with dysmorphic facies and ptosis (MONDO:0015022) is a disease caused by BRPF1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: BRPF1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 106

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder with dysmorphic facies and ptosis
Mondo ID	MONDO:0015022
OMIM	617333
Orphanet	698090
UMLS	C4310617
MedGen	934584
Is cancer (heuristic)	no

Also known as: IDDDFP · intellectual developmental disorder with dysmorphic facies and ptosis · intellectual developmental disorder with dysmorphic facies and ptosis; IDDDFP

Data availability: 106 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › autosomal dominant syndromic intellectual disability › intellectual developmental disorder with dysmorphic facies and ptosis

Related subtypes (33): Myhre syndrome, KBG syndrome, Rubinstein-Taybi syndrome due to CREBBP mutations, Mowat-Wilson syndrome, Schinzel-Giedion syndrome, intellectual disability-sparse hair-brachydactyly syndrome, Pierpont syndrome, Bohring-Opitz syndrome, hereditary cryohydrocytosis with reduced stomatin, intellectual disability-severe speech delay-mild dysmorphism syndrome, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, DYRK1A-related intellectual disability syndrome, intellectual disability, autosomal dominant 13, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, CTCF-related neurodevelopmental disorder, Bosch-Boonstra-Schaaf optic atrophy syndrome, autism spectrum disorder due to AUTS2 deficiency, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, intellectual disability, autosomal dominant 48, SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, SIN3A-related intellectual disability syndrome, Ververi-Brady syndrome 1, intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities, SATB2 associated disorder

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

106 retrieved; paginated sample, class counts are floors:

45 uncertain significance, 32 pathogenic, 20 likely pathogenic, 4 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 benign, 1 not provided, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1164021	NM_001003694.2(BRPF1):c.556C>T (p.Gln186Ter)	BRPF1	Pathogenic	no assertion criteria provided
1325379	NM_001003694.2(BRPF1):c.2798del (p.Pro933fs)	BRPF1	Pathogenic	criteria provided, multiple submitters, no conflicts
1333613	NM_001003694.2(BRPF1):c.1433G>A (p.Trp478Ter)	BRPF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1413493	NM_001003694.2(BRPF1):c.751C>T (p.Arg251Ter)	BRPF1	Pathogenic	criteria provided, multiple submitters, no conflicts
1685592	NM_001003694.2(BRPF1):c.964C>T (p.Gln322Ter)	BRPF1	Pathogenic	criteria provided, single submitter
1685593	NM_001003694.2(BRPF1):c.2027A>G (p.Lys676Arg)	BRPF1	Pathogenic	criteria provided, single submitter
1685594	NM_001003694.2(BRPF1):c.3152G>A (p.Gly1051Asp)	BRPF1	Pathogenic	criteria provided, single submitter
1700216	NM_001003694.2(BRPF1):c.1775dup (p.Arg593fs)	BRPF1	Pathogenic	criteria provided, single submitter
1703728	NM_001003694.2(BRPF1):c.2420_2433del (p.Gln807fs)	BRPF1	Pathogenic	criteria provided, multiple submitters, no conflicts
1805707	NM_001003694.2(BRPF1):c.1217dup (p.Tyr406Ter)	BRPF1	Pathogenic	criteria provided, single submitter
2435595	NM_001003694.2(BRPF1):c.598del (p.Arg200fs)	BRPF1	Pathogenic	criteria provided, single submitter
2442378	NM_001003694.2(BRPF1):c.945G>A (p.Trp315Ter)	BRPF1	Pathogenic	criteria provided, single submitter
2672220	NM_001003694.2(BRPF1):c.2545_2566dup (p.Ala856delinsGlyTer)	BRPF1	Pathogenic	criteria provided, single submitter
268185	NM_001003694.2(BRPF1):c.1052_1053del (p.Val351fs)	BRPF1	Pathogenic	criteria provided, single submitter
2691274	NM_001003694.2(BRPF1):c.940C>T (p.Gln314Ter)	BRPF1	Pathogenic	criteria provided, single submitter
3024347	NM_001003694.2(BRPF1):c.2844dup (p.Lys949fs)	BRPF1	Pathogenic	criteria provided, single submitter
3236572	NM_001003694.2(BRPF1):c.491dup (p.His164fs)	BRPF1	Pathogenic	criteria provided, single submitter
3254719	NM_001003694.2(BRPF1):c.396del (p.Asn132fs)	BRPF1	Pathogenic	criteria provided, single submitter
3384083	NM_001003694.2(BRPF1):c.2345_2346del (p.Asn782fs)	BRPF1	Pathogenic	criteria provided, single submitter
375484	NM_001003694.2(BRPF1):c.1108C>T (p.Pro370Ser)	BRPF1	Pathogenic	no assertion criteria provided
375485	NM_001003694.2(BRPF1):c.1363C>T (p.Arg455Ter)	BRPF1	Pathogenic	criteria provided, multiple submitters, no conflicts
375486	NM_001003694.2(BRPF1):c.362_363del (p.Glu121fs)	BRPF1	Pathogenic	no assertion criteria provided
375487	NM_001003694.2(BRPF1):c.2497C>T (p.Arg833Ter)	BRPF1	Pathogenic	criteria provided, single submitter
375488	NM_001003694.2(BRPF1):c.3298C>T (p.Arg1100Ter)	BRPF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375490	NM_001003694.2(BRPF1):c.2982C>G (p.Tyr994Ter)	BRPF1	Pathogenic	no assertion criteria provided
375491	NM_001003694.2(BRPF1):c.1165T>C (p.Cys389Arg)	BRPF1	Pathogenic	no assertion criteria provided
375492	NM_001003694.2(BRPF1):c.567del (p.Asp190fs)	BRPF1	Pathogenic	criteria provided, single submitter
375493	NM_001003694.2(BRPF1):c.104dup (p.Tyr35Ter)	BRPF1	Pathogenic	no assertion criteria provided
4056420	NM_001003694.2(BRPF1):c.924dup (p.Tyr309fs)	BRPF1	Pathogenic	criteria provided, single submitter
4531913	NM_001003694.2(BRPF1):c.2056C>T (p.Gln686Ter)	BRPF1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
BRPF1	Definitive	Autosomal dominant	intellectual developmental disorder with dysmorphic facies and ptosis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRPF1	Orphanet:435638	3p25.3 microdeletion syndrome
BRPF1	Orphanet:698090	Ophthalmological abnormalities-facial dysmorphism-intellectual disability syndrome
RPL10L	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation

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
BRPF1	HGNC:14255	ENSG00000156983	P55201	Peregrin	gencc,clinvar
RPL10L	HGNC:17976	ENSG00000165496	Q96L21	Ribosomal protein uL16-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRPF1	Peregrin	Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity.
RPL10L	Ribosomal protein uL16-like	Testis-specific component of the ribosome, which is required for the transition from prophase to metaphase in male meiosis I.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRPF1	Transcription factor	no		PWWP_dom, Bromodomain, Znf_PHD
RPL10L	Other/Unknown	no		Ribosomal_uL16_euk_arch, Ribosomal_uL16_dom, Ribosomal_uL16_CS_euk_arc

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
oocyte	1
secondary oocyte	1
left testis	1
right testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRPF1	254	ubiquitous	marker	oocyte, secondary oocyte, granulocyte
RPL10L	116	tissue_specific	yes	left testis, right testis, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL10L	3,564
BRPF1	1,685

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL10L	Q96L21	114
BRPF1	P55201	66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. 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
Regulation of TP53 Activity through Acetylation	1	228.4×	0.032	BRPF1
Regulation of TP53 Activity	1	66.4×	0.032	BRPF1
Peptide chain elongation	1	63.4×	0.032	RPL10L
Viral mRNA Translation	1	63.4×	0.032	RPL10L
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	62.8×	0.032	RPL10L
Selenocysteine synthesis	1	60.1×	0.032	RPL10L
Eukaryotic Translation Termination	1	60.1×	0.032	RPL10L
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	58.9×	0.032	RPL10L
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	58.9×	0.032	RPL10L
Formation of a pool of free 40S subunits	1	56.0×	0.032	RPL10L
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	55.4×	0.032	RPL10L
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	1	53.4×	0.032	RPL10L
L13a-mediated translational silencing of Ceruloplasmin expression	1	50.5×	0.032	RPL10L
SRP-dependent cotranslational protein targeting to membrane	1	50.1×	0.032	RPL10L
GTP hydrolysis and joining of the 60S ribosomal subunit	1	50.1×	0.032	RPL10L
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1	48.8×	0.032	RPL10L
Chromatin organization	1	40.8×	0.035	BRPF1
HATs acetylate histones	1	39.6×	0.035	BRPF1
Chromatin modifying enzymes	1	36.1×	0.036	BRPF1
Regulation of expression of SLITs and ROBOs	1	34.6×	0.036	RPL10L
Transcriptional Regulation by TP53	1	31.0×	0.037	BRPF1
Major pathway of rRNA processing in the nucleolus and cytosol	1	30.9×	0.037	RPL10L
RNA Polymerase II Transcription	1	11.3×	0.094	BRPF1
Gene expression (Transcription)	1	8.9×	0.113	BRPF1
Generic Transcription Pathway	1	7.5×	0.128	BRPF1

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
regulation of developmental process	1	1203.7×	0.005	BRPF1
regulation of hemopoiesis	1	766.0×	0.005	BRPF1
ribosomal large subunit assembly	1	702.2×	0.005	RPL10L
male meiosis I	1	290.6×	0.009	RPL10L
translation	1	51.4×	0.043	RPL10L
chromatin remodeling	1	36.5×	0.050	BRPF1
spermatogenesis	1	17.6×	0.077	RPL10L
regulation of DNA-templated transcription	1	15.8×	0.077	BRPF1
cell differentiation	1	14.6×	0.077	RPL10L
positive regulation of DNA-templated transcription	1	14.0×	0.077	BRPF1
regulation of transcription by RNA polymerase II	1	5.8×	0.164	BRPF1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRPF1	0	0
RPL10L	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
BRPF1	175	Binding:172, Functional:3

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRPF1	175

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

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	2	BRPF1, RPL10L

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BRPF1	175	—
RPL10L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.