Developmental delay with short stature, dysmorphic facial features, and sparse hair 2

Summary

Developmental delay with short stature, dysmorphic facial features, and sparse hair 2 (MONDO:0100217) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	developmental delay with short stature, dysmorphic facial features, and sparse hair 2
Mondo ID	MONDO:0100217
OMIM	620062
DOID	DOID:0070478
UMLS	C5774223
MedGen	1823996
Is cancer (heuristic)	no

Also known as: DEDSSH2 · diphthamide deficiency syndrome 2

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › developmental delay with short stature, dysmorphic facial features, and sparse hair › developmental delay with short stature, dysmorphic facial features, and sparse hair 2

Related subtypes (1): developmental delay with short stature, dysmorphic facial features, and sparse hair 1

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

5 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1687066	NM_001384.5(DPH2):c.1429C>T (p.Arg477Ter)	DPH2	Likely pathogenic	criteria provided, single submitter
2671662	NM_001384.5(DPH2):c.224C>G (p.Ser75Ter)	DPH2	Likely pathogenic	criteria provided, single submitter
3065569	NM_001384.5(DPH2):c.844del (p.Arg282fs)	DPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
872918	NM_001384.5(DPH2):c.922C>T (p.Gln308Ter)	LOC126805726	Conflicting classifications of pathogenicity	no assertion criteria provided
872919	NM_001384.5(DPH2):c.601C>T (p.Arg201Cys)	LOC126805726	Conflicting classifications of pathogenicity	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 1 · 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
DPH2	Moderate	Autosomal recessive	developmental delay with short stature, dysmorphic facial features, and sparse hair 2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DPH2	Orphanet:459061	Craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DPH2	HGNC:3004	ENSG00000132768	Q9BQC3	2-(3-amino-3-carboxypropyl)histidine synthase subunit 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DPH2	2-(3-amino-3-carboxypropyl)histidine synthase subunit 2	Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DPH2	Other/Unknown	no		DHP2, DPH1/DPH2, DPH1/DPH2_1

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
granulocyte	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DPH2	249	ubiquitous	marker	gastrocnemius, muscle of leg, granulocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DPH2	1,405

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DPH2	Q9BQC3	83.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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
Synthesis of diphthamide-EEF2	1	1427.5×	7e-04	DPH2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein histidyl modification to diphthamide	1	2407.4×	4e-04	DPH2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
DPH2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	DPH2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DPH2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.