chromosome 17P13.3, telomeric, duplication syndrome

Summary

chromosome 17P13.3, telomeric, duplication syndrome (MONDO:0012944) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chromosome 17P13.3, telomeric, duplication syndrome
Mondo ID	MONDO:0012944
MeSH	C567245
OMIM	612576
UMLS	C2675492
MedGen	390813
GARD	0015572
Is cancer (heuristic)	no

Also known as: chromosome 17P13.3, telomeric, duplication syndrome

Data availability: 4 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › tibial aplasia-ectrodactyly syndrome › chromosome 17P13.3, telomeric, duplication syndrome

Related subtypes (2): split-hand/foot malformation with long bone deficiency 1, split-hand/foot malformation with long bone deficiency 2

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1695397	Single allele	BHLHA9	Pathogenic	criteria provided, single submitter
625578	GRCh37/hg19 17p13.3-13.2(chr17:47546-6287620)	CRK	Pathogenic	criteria provided, single submitter
625580	GRCh37/hg19 17p13.3(chr17:1084016-1278527)	TRARG1	Pathogenic	criteria provided, single submitter
4795127	NC_000017.11:g.(1270543_1298284)dup		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BHLHA9	Orphanet:157801	Mesoaxial synostotic syndactyly with phalangeal reduction
BHLHA9	Orphanet:1986	Gollop-Wolfgang complex
BHLHA9	Orphanet:3329	Tibial aplasia-ectrodactyly syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CRK	HGNC:2362	ENSG00000167193	P46108	Adapter molecule crk	clinvar
TRARG1	HGNC:29592	ENSG00000184811	Q8IXB3	Trafficking regulator of GLUT4 1	clinvar
BHLHA9	HGNC:35126	ENSG00000205899	Q7RTU4	Class A basic helix-loop-helix protein 9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRK	Adapter molecule crk	Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1.
TRARG1	Trafficking regulator of GLUT4 1	Regulates insulin-mediated adipose tissue glucose uptake and transport by modulation of SLC2A4 recycling.
BHLHA9	Class A basic helix-loop-helix protein 9	Transcription factor, which play a role in limb development.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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
Scaffold/PPI	1	5.8×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRK	Scaffold/PPI	no		SH2, SH3_domain, CRK_SH3_N
TRARG1	Other/Unknown	no		CD225/Dispanin_fam, CD225/Dispanin
BHLHA9	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of sigmoid colon	1
oocyte	1
secondary oocyte	1
adipose tissue	1
omental fat pad	1
subcutaneous adipose tissue	1
Brodmann (1909) area 9	1
dorsolateral prefrontal cortex	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRK	300	ubiquitous	marker	secondary oocyte, oocyte, mucosa of sigmoid colon
TRARG1	103	tissue_specific	yes	subcutaneous adipose tissue, adipose tissue, omental fat pad
BHLHA9	28	tissue_specific	yes	primordial germ cell in gonad, Brodmann (1909) area 9, dorsolateral prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRK	3,441
TRARG1	785
BHLHA9	405

Intra-cohort edges

A	B	Sources
BHLHA9	CRK	string_interaction
BHLHA9	TRARG1	string_interaction
CRK	TRARG1	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRK	P46108	10

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BHLHA9	Q7RTU4	66.46
TRARG1	Q8IXB3	54.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 3 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
ARMS-mediated activation	1	1631.4×	0.003	CRK
MET receptor recycling	1	1142.0×	0.003	CRK
MET activates RAP1 and RAC1	1	1038.2×	0.003	CRK
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	815.7×	0.003	CRK
p130Cas linkage to MAPK signaling for integrins	1	761.3×	0.003	CRK
Regulation of signaling by CBL	1	496.5×	0.003	CRK
Downstream signal transduction	1	380.7×	0.004	CRK
FCGR3A-mediated phagocytosis	1	187.2×	0.006	CRK
Regulation of actin dynamics for phagocytic cup formation	1	184.2×	0.006	CRK
VEGFA-VEGFR2 Pathway	1	139.3×	0.007	CRK

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to hepatocyte growth factor	1	5617.3×	0.005	CRK
vesicle fusion to plasma membrane	1	5617.3×	0.005	TRARG1
helper T cell diapedesis	1	2808.7×	0.005	CRK
response to cholecystokinin	1	2808.7×	0.005	CRK
postsynaptic specialization assembly	1	1404.3×	0.006	CRK
cerebellar neuron development	1	1404.3×	0.006	CRK
endosome to plasma membrane protein transport	1	1123.5×	0.007	TRARG1
glucose import in response to insulin stimulus	1	936.2×	0.007	TRARG1
regulation of T cell migration	1	802.5×	0.007	CRK
response to yeast	1	702.2×	0.007	CRK
regulation of cell adhesion mediated by integrin	1	624.1×	0.007	CRK
positive regulation of skeletal muscle acetylcholine-gated channel clustering	1	624.1×	0.007	CRK
cellular response to endothelin	1	468.1×	0.007	CRK
enzyme-linked receptor protein signaling pathway	1	432.1×	0.007	CRK
negative regulation of wound healing	1	432.1×	0.007	CRK
cellular response to insulin-like growth factor stimulus	1	432.1×	0.007	CRK
negative regulation of cell motility	1	432.1×	0.007	CRK
reelin-mediated signaling pathway	1	401.2×	0.007	CRK
response to peptide	1	374.5×	0.007	CRK
positive regulation of smooth muscle cell migration	1	330.4×	0.007	CRK
regulation of dendrite development	1	330.4×	0.007	CRK
cellular response to nitric oxide	1	312.1×	0.007	CRK
negative regulation of natural killer cell mediated cytotoxicity	1	295.6×	0.007	CRK
regulation of intracellular signal transduction	1	295.6×	0.007	CRK
developmental process	1	224.7×	0.009	BHLHA9
positive regulation of Rac protein signal transduction	1	216.1×	0.009	CRK
protein localization to membrane	1	200.6×	0.010	CRK
Rac protein signal transduction	1	187.2×	0.010	CRK
regulation of GTPase activity	1	170.2×	0.011	CRK
response to hydrogen peroxide	1	156.0×	0.011	CRK

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CRK	0	0
TRARG1	0	0
BHLHA9	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
CRK	9	Binding:9

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	CRK, TRARG1, BHLHA9

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CRK	9	—
TRARG1	0	—
BHLHA9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.