Chromosome 3q29 microdeletion syndrome

Summary

Chromosome 3q29 microdeletion syndrome (MONDO:0012269) is a disease with 4 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 4
• ClinVar variants: 8
• Phenotypes (HPO): 44

Clinical features

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0000232	Everted lower lip vermilion	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000322	Short philtrum	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000400	Macrotia	Frequent (30-79%)
HP:0000426	Prominent nasal bridge	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000085	Horseshoe kidney	Occasional (5-29%)
HP:0000164	Abnormality of the dentition	Occasional (5-29%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000275	Narrow face	Occasional (5-29%)
HP:0000276	Long face	Occasional (5-29%)
HP:0000324	Facial asymmetry	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0000678	Dental crowding	Occasional (5-29%)
HP:0000709	Psychosis	Occasional (5-29%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000739	Anxiety	Occasional (5-29%)
HP:0000767	Pectus excavatum	Occasional (5-29%)
HP:0000768	Pectus carinatum	Occasional (5-29%)
HP:0001000	Abnormality of skin pigmentation	Occasional (5-29%)
HP:0001182	Tapered finger	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001611	Hypernasal speech	Occasional (5-29%)
HP:0001643	Patent ductus arteriosus	Occasional (5-29%)
HP:0001682	Subvalvular aortic stenosis	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002092	Pulmonary arterial hypertension	Occasional (5-29%)
HP:0003196	Short nose	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0007302	Bipolar affective disorder	Occasional (5-29%)
HP:0008416	Six lumbar vertebrae	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 3q29 microdeletion syndrome
Mondo ID	MONDO:0012269
MeSH	C567184
OMIM	609425
Orphanet	65286
DOID	DOID:0060419
SNOMED CT	716456000
UMLS	C2674949
MedGen	393265
GARD	0011974
Is cancer (heuristic)	no

Also known as: 3q subtelomere deletion syndrome · 3q29 deletion · 3q29 deletion syndrome · 3q29 microdeletion syndrome · 3qter deletion · chromosome 3q29 microdeletion syndrome, isolated cases · Del(3)(q29) · monosomy 3q29 · monosomy 3qter

Data availability: 8 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › chromosomal disorder › syndrome caused by partial chromosomal deletion › partial deletion of chromosome 3 › partial deletion of the long arm of chromosome 3 › chromosome 3q29 microdeletion syndrome

Related subtypes (4): chromosome 3q13.31 deletion syndrome, blepharophimosis-epicanthus inversus-ptosis due to 3q23 rearrangement syndrome, 3q26q27 microdeletion syndrome, 3q26q28 deletion 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

8 retrieved; paginated sample, class counts are floors:

7 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4795132	NC_000003.12:g.(196051921_197556355)del		Pathogenic	criteria provided, single submitter
1703655	GRCh37/hg19 3q29(chr3:195703615-197386180)	BDH1	Pathogenic	no assertion criteria provided
4082236	Single allele	BDH1	Pathogenic	criteria provided, single submitter
1679598	Single allele	CEP19	Pathogenic	criteria provided, single submitter
4082017	NC_000003.12:g.196051941_197546443del	LOC111828515	Pathogenic	no assertion criteria provided
4081946	NC_000003.12:g.196051932_197546453del	LOC129938281	Pathogenic	no assertion criteria provided
267260	GRCh37/hg19 3q29(chr3:195756054-197344665)x1	MELTF	Pathogenic	no assertion criteria provided
1330171	GRCh37/hg19 3q29(chr3:194790394-197961930)x3	ACAP2	Uncertain significance	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
CEP19	Orphanet:110	Bardet-Biedl syndrome
CEP19	Orphanet:397615	Obesity due to CEP19 deficiency

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BDH1	HGNC:1027	ENSG00000161267	Q02338	D-beta-hydroxybutyrate dehydrogenase, mitochondrial	clinvar
ACAP2	HGNC:16469	ENSG00000114331	Q15057	Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2	clinvar
CEP19	HGNC:28209	ENSG00000174007	Q96LK0	Centrosomal protein of 19 kDa	clinvar
MELTF	HGNC:7037	ENSG00000163975	P08582	Melanotransferrin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACAP2	Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2	GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6).
CEP19	Centrosomal protein of 19 kDa	Required for ciliation.
MELTF	Melanotransferrin	Involved in iron cellular uptake.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 3 · 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
Scaffold/PPI	1	4.3×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BDH1	Other/Unknown	no		SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
ACAP2	Scaffold/PPI	no		ArfGAP_dom, PH_domain, Ankyrin_rpt
CEP19	Other/Unknown	no		CEP19
MELTF	Other/Unknown	no		Transferrin-like_dom, Transferrin, Transferrin_Fe_BS

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
mucosa of transverse colon	1
right lobe of liver	1
bone marrow cell	1
epithelium of nasopharynx	1
superficial temporal artery	1
blood	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
decidua	1
parotid gland	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BDH1	134	ubiquitous	marker	right lobe of liver, liver, mucosa of transverse colon
ACAP2	288	ubiquitous	marker	epithelium of nasopharynx, bone marrow cell, superficial temporal artery
CEP19	214	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, blood
MELTF	228	ubiquitous	marker	tibia, parotid gland, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BDH1	1,297
ACAP2	1,288
CEP19	1,037
MELTF	988

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ACAP2	Q15057	1
MELTF	P08582	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BDH1	Q02338	87.23
CEP19	Q96LK0	82.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 4 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
Utilization of Ketone Bodies	1	1427.5×	0.005	BDH1
Ketone body metabolism	1	951.7×	0.005	BDH1
Synthesis of Ketone Bodies	1	713.8×	0.005	BDH1
Post-translational modification: synthesis of GPI-anchored proteins	1	84.0×	0.030	MELTF
Mitochondrial protein degradation	1	57.1×	0.033	BDH1
Post-translational protein phosphorylation	1	50.1×	0.033	MELTF
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.033	MELTF
Metabolism of lipids	1	15.8×	0.078	BDH1
Metabolism of proteins	1	6.2×	0.165	BDH1
Metabolism	1	5.8×	0.165	BDH1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
trans-Golgi to periciliary membrane compartment transport	1	4213.0×	0.003	CEP19
actin filament-based process	1	2106.5×	0.003	ACAP2
positive regulation of plasminogen activation	1	468.1×	0.007	MELTF
microtubule anchoring at centrosome	1	351.1×	0.007	CEP19
positive regulation of extracellular matrix disassembly	1	300.9×	0.007	MELTF
negative regulation of substrate adhesion-dependent cell spreading	1	280.9×	0.007	MELTF
iron ion transport	1	221.7×	0.007	MELTF
cellular response to nerve growth factor stimulus	1	117.0×	0.012	ACAP2
steroid metabolic process	1	84.3×	0.014	BDH1
endocytic recycling	1	66.9×	0.016	ACAP2
cilium assembly	1	18.4×	0.053	CEP19

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
BDH1	0	0
ACAP2	0	0
CEP19	0	0
MELTF	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	4	BDH1, ACAP2, CEP19, MELTF

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BDH1	0	—
ACAP2	0	—
CEP19	0	—
MELTF	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.