Chromosome 17q12 duplication syndrome

Summary

Chromosome 17q12 duplication syndrome (MONDO:0013796) is a disease with 4 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 4
• ClinVar variants: 6
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		118	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Point prevalence	1-9 / 1 000 000	0.46	Denmark	Validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0002539	Cortical dysplasia	Frequent (30-79%)
HP:0000175	Cleft palate	Occasional (5-29%)
HP:0000490	Deeply set eye	Occasional (5-29%)
HP:0000501	Glaucoma	Occasional (5-29%)
HP:0000568	Microphthalmia	Occasional (5-29%)
HP:0000664	Synophrys	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001561	Polyhydramnios	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0002463	Language impairment	Occasional (5-29%)
HP:0002575	Tracheoesophageal fistula	Occasional (5-29%)
HP:0003468	Abnormal vertebral morphology	Occasional (5-29%)
HP:0006101	Finger syndactyly	Occasional (5-29%)
HP:0100716	Self-injurious behavior	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 17q12 duplication syndrome
Mondo ID	MONDO:0013796
OMIM	614526
Orphanet	261272
DOID	DOID:0060433
SNOMED CT	764435003
UMLS	C3281137
MedGen	482767
GARD	0013296
Is cancer (heuristic)	no

Also known as: 17q12 duplication · 17q12 microduplication · 17q12 microduplication syndrome · chromosome 17q12 duplication syndrome · dup(17)(q12) · recurrent duplication of 17q12 · trisomy 17q12

Data availability: 6 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 duplication › partial duplication of chromosome 17 › partial duplication of the long arm of chromosome 17 › chromosome 17q12 duplication syndrome

Related subtypes (5): chromosome 17q21.31 duplication syndrome, familial clubfoot due to 17q23.1q23.2 microduplication, PMP22-RAI1 contiguous gene duplication syndrome, 17q11.2 microduplication syndrome, distal trisomy 17q

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

6 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
223237	Single allele		Pathogenic	no assertion criteria provided
625651	GRCh37/hg19 17q12(chr17:34819191-36104803)	AATF	Pathogenic	criteria provided, single submitter
625680	GRCh37/hg19 17q12(chr17:34842059-36214026)	AATF	Pathogenic	criteria provided, single submitter
625612	GRCh37/hg19 17q12(chr17:34848678-36194230)	GGNBP2	Pathogenic	criteria provided, single submitter
625732	GRCh37/hg19 17q12(chr17:34437475-36214026)	TADA2A	Pathogenic	criteria provided, single submitter
4074295	GRCh37/hg19 17q12(chr17:34822465-36283612)x3	MRM1	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

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TADA2A	HGNC:11531	ENSG00000276234	O75478	Transcriptional adapter 2-alpha	clinvar
AATF	HGNC:19235	ENSG00000275700	Q9NY61	Protein AATF	clinvar
GGNBP2	HGNC:19357	ENSG00000278311	Q9H3C7	Gametogenetin-binding protein 2	clinvar
MRM1	HGNC:26202	ENSG00000278619	Q6IN84	rRNA methyltransferase 1, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TADA2A	Transcriptional adapter 2-alpha	Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.
AATF	Protein AATF	Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit.
GGNBP2	Gametogenetin-binding protein 2	May be involved in spermatogenesis.
MRM1	rRNA methyltransferase 1, mitochondrial	S-adenosyl-L-methionine-dependent 2’-O-ribose methyltransferase that catalyzes the formation of 2’-O-methylguanosine at position 1145 (Gm1145) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modif…

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
Enzyme (other)	1	3.0×	0.605
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TADA2A	Transcription factor	no		Znf_ZZ, SANT/Myb, SWIRM
AATF	Other/Unknown	no		AATF_C, AATF, AATF/Bfr2
GGNBP2	Other/Unknown	no		GGNBP2
MRM1	Enzyme (other)	yes	2.1.1.B125	SpoU_MeTrfase, rRNA_MeTrfase_TrmH, SpoU_subst-bd

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
calcaneal tendon	1
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1
granulocyte	1
leukocyte	1
monocyte	1
left testis	1
right testis	1
testis	1
apex of heart	1
mucosa of transverse colon	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TADA2A	134	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon, corpus callosum
AATF	134	ubiquitous	marker	monocyte, leukocyte, granulocyte
GGNBP2	134	ubiquitous	marker	left testis, right testis, testis
MRM1	130	ubiquitous	yes	primordial germ cell in gonad, mucosa of transverse colon, apex of heart

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AATF	3,194
MRM1	2,583
GGNBP2	2,235
TADA2A	1,607

Intra-cohort edges

A	B	Sources
AATF	GGNBP2	string_interaction
AATF	TADA2A	intact
GGNBP2	MRM1	string_interaction
GGNBP2	TADA2A	string_interaction
MRM1	TADA2A	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AATF	Q9NY61	3
TADA2A	O75478	1
GGNBP2	Q9H3C7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MRM1	Q6IN84	78.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
rRNA processing in the mitochondrion	1	634.4×	0.010	MRM1
rRNA modification in the mitochondrion	1	439.2×	0.010	MRM1
Cell death signalling via NRAGE, NRIF and NADE	1	109.8×	0.018	AATF
p75 NTR receptor-mediated signalling	1	93.6×	0.018	AATF
NRAGE signals death through JNK	1	92.1×	0.018	AATF
rRNA processing	1	73.2×	0.018	MRM1
Death Receptor Signaling	1	69.6×	0.018	AATF
Metabolism of RNA	1	20.8×	0.053	MRM1
Signal Transduction	1	5.1×	0.187	AATF

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
rRNA 2’-O-methylation	1	1404.3×	0.008	MRM1
rRNA modification	1	842.6×	0.008	MRM1
negative regulation of receptor signaling pathway via STAT	1	842.6×	0.008	GGNBP2
negative regulation of amyloid precursor protein biosynthetic process	1	526.6×	0.010	AATF
embryonic cleavage	1	421.3×	0.010	AATF
labyrinthine layer blood vessel development	1	200.6×	0.016	GGNBP2
regulation of cell division	1	191.5×	0.016	TADA2A
negative regulation of apoptotic signaling pathway	1	140.4×	0.019	AATF
regulation of embryonic development	1	82.6×	0.028	TADA2A
regulation of mitotic cell cycle	1	60.2×	0.033	AATF
ribosomal small subunit biogenesis	1	56.9×	0.033	AATF
rRNA processing	1	35.4×	0.049	MRM1
regulation of cell cycle	1	18.6×	0.079	TADA2A
chromatin remodeling	1	18.2×	0.079	TADA2A
negative regulation of gene expression	1	17.3×	0.079	GGNBP2
negative regulation of cell population proliferation	1	10.5×	0.120	GGNBP2
cell adhesion	1	9.4×	0.127	AATF
spermatogenesis	1	8.8×	0.127	GGNBP2
regulation of DNA-templated transcription	1	7.9×	0.134	TADA2A
cell differentiation	1	7.3×	0.137	GGNBP2
regulation of transcription by RNA polymerase II	1	2.9×	0.302	TADA2A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TADA2A	0	0
AATF	0	0
GGNBP2	0	0
MRM1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MRM1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MRM1	2.1.1.B125

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	1	MRM1
E	Difficult family or no structure, no drug	3	TADA2A, AATF, GGNBP2

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)
TADA2A	0	—
AATF	0	—
GGNBP2	0	—
MRM1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.