3p- syndrome

Summary

3p- syndrome (MONDO:0013424) is a disease with 4 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 4
• ClinVar variants: 4
• Phenotypes (HPO): 34

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		34	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

34 HPO clinical features (Orphanet curated; top 34 by frequency):

HPO ID	Term	Frequency
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000343	Long philtrum	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000506	Telecanthus	Very frequent (80-99%)
HP:0000508	Ptosis	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0100543	Cognitive impairment	Very frequent (80-99%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000175	Cleft palate	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000248	Brachycephaly	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0001162	Postaxial hand polydactyly	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0002714	Downturned corners of mouth	Frequent (30-79%)
HP:0006695	Atrioventricular canal defect	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000233	Thin vermilion border	Occasional (5-29%)
HP:0000325	Triangular face	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0000581	Blepharophimosis	Occasional (5-29%)
HP:0000960	Sacral dimple	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001537	Umbilical hernia	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0004467	Preauricular pit	Occasional (5-29%)
HP:0007670	Abnormal vestibulo-ocular reflex	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	3p- syndrome
Mondo ID	MONDO:0013424
MeSH	C536804
OMIM	613792
Orphanet	1620
DOID	DOID:0060417
NCIT	C41377
SNOMED CT	763528002
UMLS	C4706503
MedGen	1643555
GARD	0003750
NORD	951
Is cancer (heuristic)	no

Also known as: 3p deletion · 3p monosomy · 3p- syndrome · Chromosome 3, Monosomy 3p · chromosome 3, monosomy 3p25 · chromosome 3p deletion · chromosome 3p- syndrome · chromosome 3pter-p25 deletion syndrome · Del(3p) syndrome · deletion 3p · deletion 3p25 · distal 3p deletion · distal monosomy 3p · distal monosomy type 3p · monosomy 3p · monosomy 3pter · partial monosomy 3p · telomeric monosomy 3p

Data availability: 4 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 short arm of chromosome 3 › 3p- syndrome

Related subtypes (1): 3p25.3 microdeletion 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

4 retrieved; paginated sample, class counts are floors:

4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2580893	GRCh37/hg19 3p26.2-25.3(chr3:3691505-9917651)x1	ARL8B	Pathogenic	no assertion criteria provided
3900604	GRCh37/hg19 3p25.3(chr3:10239102-11732086)x1	ATG7	Pathogenic	criteria provided, single submitter
1703229	Single allele	FGD5	Pathogenic	criteria provided, single submitter
818229	NC_000003.11:g.9387774_9503839del116066	THUMPD3	Pathogenic	criteria provided, single submitter

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
ATG7	HGNC:16935	ENSG00000197548	O95352	Ubiquitin-like modifier-activating enzyme ATG7	clinvar
FGD5	HGNC:19117	ENSG00000154783	Q6ZNL6	FYVE, RhoGEF and PH domain-containing protein 5	clinvar
THUMPD3	HGNC:24493	ENSG00000134077	Q9BV44	tRNA (guanine(6)-N(2))-methyltransferase THUMP3	clinvar
ARL8B	HGNC:25564	ENSG00000134108	Q9NVJ2	ADP-ribosylation factor-like protein 8B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATG7	Ubiquitin-like modifier-activating enzyme ATG7	E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy.
FGD5	FYVE, RhoGEF and PH domain-containing protein 5	Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP.
THUMPD3	tRNA (guanine(6)-N(2))-methyltransferase THUMP3	Catalytic subunit of the THUMPD3-TRM112 methyltransferase complex, that specifically mediates the S-adenosyl-L-methionine-dependent N(2)-methylation of guanosine nucleotide at position 6 (m2G6) in tRNAs.
ARL8B	ADP-ribosylation factor-like protein 8B	Small GTPase which cycles between active GTP-bound and inactive GDP-bound states.

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
Transcription factor	1	2.1×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATG7	Other/Unknown	no		ThiF_NAD_FAD-bd, Atg7, Atg7_N
FGD5	Transcription factor	no		DH_dom, Znf_FYVE, PH_domain
THUMPD3	Other/Unknown	no		RlmKL-like_Mtase, THUMP_dom, SAM-dependent_MTases_sf
ARL8B	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

4 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
leukocyte	1
monocyte	1
mononuclear cell	1
layer of synovial tissue	1
synovial joint	1
tendon of biceps brachii	1
left testis	1
right testis	1
sperm	1
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATG7	232	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
FGD5	220	broad	marker	synovial joint, layer of synovial tissue, tendon of biceps brachii
THUMPD3	253	ubiquitous	marker	sperm, left testis, right testis
ARL8B	292	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATG7	5,169
ARL8B	2,713
THUMPD3	1,627
FGD5	1,395

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARL8B	Q9NVJ2	3
FGD5	Q6ZNL6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATG7	O95352	88.06
THUMPD3	Q9BV44	78.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Dengue Virus Attachment and Entry	1	129.8×	0.047	ATG7
Oncogenic MAPK signaling	1	124.1×	0.047	ATG7
Signaling by BRAF and RAF1 fusions	1	85.2×	0.047	ATG7
Autophagy	1	74.2×	0.047	ATG7
Macroautophagy	1	57.7×	0.048	ATG7
Class I MHC mediated antigen processing & presentation	1	35.0×	0.061	ATG7
RAC1 GTPase cycle	1	30.5×	0.061	FGD5
Diseases of signal transduction by growth factor receptors and second messengers	1	28.4×	0.061	ATG7
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.083	ATG7
Adaptive Immune System	1	14.9×	0.092	ATG7
Innate Immune System	1	12.8×	0.098	ATG7
Neutrophil degranulation	1	11.5×	0.099	ATG7
Disease	1	6.5×	0.148	ATG7
Immune System	1	6.5×	0.148	ATG7

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
antigen processing and presentation of polysaccharide antigen via MHC class II	1	4213.0×	0.003	ARL8B
antigen processing and presentation following phagocytosis	1	4213.0×	0.003	ARL8B
viral exocytosis	1	4213.0×	0.003	ARL8B
positive regulation of protein modification process	1	2106.5×	0.004	ATG7
endosome to lysosome transport of low-density lipoprotein particle	1	2106.5×	0.004	ARL8B
protein modification by small protein conjugation	1	1404.3×	0.004	ATG7
protein localization to early endosome	1	1404.3×	0.004	ARL8B
calcium ion regulated lysosome exocytosis	1	1404.3×	0.004	ARL8B
protein lipidation	1	842.6×	0.005	ATG7
cellular response to hyperoxia	1	842.6×	0.005	ATG7
cellular response to nitrogen starvation	1	383.0×	0.009	ATG7
early endosome to Golgi transport	1	324.1×	0.009	ARL8B
phagosome-lysosome fusion	1	324.1×	0.009	ARL8B
protein transport	2	21.9×	0.009	ATG7, ARL8B
autophagosome-lysosome fusion	1	300.9×	0.009	ARL8B
late endosome to lysosome transport	1	247.8×	0.010	ARL8B
piecemeal microautophagy of the nucleus	1	234.1×	0.010	ATG7
cellular response to stress	1	210.7×	0.011	ATG7
filopodium assembly	1	162.0×	0.013	FGD5
plasma membrane repair	1	145.3×	0.013	ARL8B
anterograde axonal transport	1	145.3×	0.013	ARL8B
tRNA methylation	1	145.3×	0.013	THUMPD3
lysosome localization	1	131.7×	0.013	ARL8B
regulation of GTPase activity	1	127.7×	0.013	FGD5
natural killer cell mediated cytotoxicity	1	108.0×	0.015	ARL8B
mitophagy	1	79.5×	0.020	ATG7
regulation of circadian rhythm	1	64.8×	0.023	ATG7
rhythmic process	1	62.9×	0.023	ATG7
macroautophagy	1	60.2×	0.023	ATG7
autophagosome assembly	1	56.2×	0.024	ATG7

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 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
ATG7	0	0
FGD5	0	0
THUMPD3	0	0
ARL8B	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
ATG7	12	Binding:12
ARL8B	2	Binding:2

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	ATG7, FGD5, THUMPD3, ARL8B

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)
ATG7	12	—
FGD5	0	—
THUMPD3	0	—
ARL8B	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.