Microcephaly, epilepsy, and diabetes syndrome 2

Summary

Microcephaly, epilepsy, and diabetes syndrome 2 (MONDO:0025690) is a disease caused by YIPF5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: YIPF5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly, epilepsy, and diabetes syndrome 2
Mondo ID	MONDO:0025690
OMIM	619278
UMLS	C5543294
MedGen	1782107
GARD	0018439
Is cancer (heuristic)	no

Also known as: MEDS2

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › microcephaly, epilepsy, and diabetes syndrome › microcephaly, epilepsy, and diabetes syndrome 2

Related subtypes (1): microcephaly, epilepsy, and diabetes syndrome 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

6 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1064543	NM_030799.9(YIPF5):c.317_319del (p.Lys106del)	LOC126807536	Pathogenic	no assertion criteria provided
1064544	NM_030799.9(YIPF5):c.293T>G (p.Ile98Ser)	LOC126807536	Pathogenic	no assertion criteria provided
1064546	NM_030799.9(YIPF5):c.290G>T (p.Gly97Val)	LOC126807536	Pathogenic	no assertion criteria provided
1064542	NM_030799.9(YIPF5):c.542C>T (p.Ala181Val)	YIPF5	Pathogenic	no assertion criteria provided
1064545	NM_030799.9(YIPF5):c.652T>A (p.Trp218Arg)	YIPF5	Pathogenic	no assertion criteria provided
2438632	NM_030799.9(YIPF5):c.524T>A (p.Val175Asp)	YIPF5	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
YIPF5	Strong	Autosomal recessive	microcephaly, epilepsy, and diabetes syndrome 2	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
YIPF5	Orphanet:306558	Primary microcephaly-epilepsy-permanent neonatal diabetes 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
YIPF5	HGNC:24877	ENSG00000145817	Q969M3	Protein YIPF5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
YIPF5	Protein YIPF5	Plays a role in transport between endoplasmic reticulum and Golgi.

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)
YIPF5	Other/Unknown	no		Yip1_dom, Yip1/4-like

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
jejunal mucosa	1
mucosa of paranasal sinus	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
YIPF5	276	ubiquitous	marker	jejunal mucosa, mucosa of paranasal sinus, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
YIPF5	1,326

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
YIPF5	Q969M3	66.45

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
vesicle fusion with Golgi apparatus	1	2407.4×	1e-03	YIPF5
regulation of ER to Golgi vesicle-mediated transport	1	2106.5×	1e-03	YIPF5
insulin processing	1	1685.2×	1e-03	YIPF5
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.009	YIPF5
protein transport	1	43.9×	0.023	YIPF5

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
YIPF5	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
YIPF5	1	Binding:1

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	YIPF5

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)
YIPF5	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.