Microcephaly 19, primary, autosomal recessive

Summary

Microcephaly 19, primary, autosomal recessive (MONDO:0054716) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 19, primary, autosomal recessive
Mondo ID	MONDO:0054716
OMIM	617800
DOID	DOID:0070281
UMLS	C4540488
MedGen	1616860
GARD	0016253
Is cancer (heuristic)	no

Also known as: MCPH19

Data availability: 6 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive primary microcephaly › microcephaly 19, primary, autosomal recessive

Related subtypes (28): microcephaly 1, primary, autosomal recessive, microcephaly with simplified gyral pattern, microcephaly 2, primary, autosomal recessive, with or without cortical malformations, microcephaly 4, primary, autosomal recessive, microcephaly 3, primary, autosomal recessive, microcephaly 5, primary, autosomal recessive, microcephaly 7, primary, autosomal recessive, microcephaly 8, primary, autosomal recessive, microcephaly 9, primary, autosomal recessive, microcephalic primordial dwarfism due to ZNF335 deficiency, microcephaly 11, primary, autosomal recessive, microcephaly 13, primary, autosomal recessive, microcephaly 12, primary, autosomal recessive, microcephaly 14, primary, autosomal recessive, microcephaly 15, primary, autosomal recessive, microcephaly 16, primary, autosomal recessive, microcephaly 17, primary, autosomal recessive, microcephaly 28, primary, autosomal recessive, microcephaly 29, primary, autosomal recessive, microcephaly 24, primary, autosomal recessive, microcephaly 25, primary, autosomal recessive, microcephaly 20, primary, autosomal recessive, microcephaly 21, primary, autosomal recessive, microcephaly 22, primary, autosomal recessive, microcephaly 23, primary, autosomal recessive, microcephaly with or without short stature, microcephaly 30, primary, autosomal recessive, microcephaly 31, primary, autosomal recessive

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:

3 benign, 2 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3370487	NM_004766.3(COPB2):c.660_661del (p.Val222fs)	COPB2	Pathogenic	criteria provided, multiple submitters, no conflicts
446713	NM_004766.3(COPB2):c.760C>T (p.Arg254Cys)	COPB2	Pathogenic	no assertion criteria provided
1224936	NM_004766.3(COPB2):c.141+20G>T	COPB2	Benign	criteria provided, multiple submitters, no conflicts
1255401	NM_004766.3(COPB2):c.2626-20C>A	COPB2	Benign	criteria provided, multiple submitters, no conflicts
1255402	NM_004766.3(COPB2):c.1095-23T>C	COPB2	Benign	criteria provided, multiple submitters, no conflicts
1585446	NM_004766.3(COPB2):c.342T>C (p.Ile114=)	COPB2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
COPB2	Supportive	Autosomal recessive	autosomal recessive primary microcephaly	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COPB2	Orphanet:2512	Autosomal recessive primary microcephaly

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
COPB2	HGNC:2232	ENSG00000184432	P35606	Coatomer subunit beta'	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COPB2	Coatomer subunit beta'	The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Go…

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COPB2	Scaffold/PPI	no		WD40_rpt, Beta-prop_COPA/B_2nd, WD40/YVTN_repeat-like_dom_sf

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
parotid gland	1
stromal cell of endometrium	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COPB2	295	ubiquitous	marker	parotid gland, stromal cell of endometrium, type B pancreatic cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COPB2	2,982

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COPB2	P35606	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
COPI-dependent Golgi-to-ER retrograde traffic	1	110.9×	0.009	COPB2
COPI-mediated anterograde transport	1	109.8×	0.009	COPB2

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
intra-Golgi vesicle-mediated transport	1	526.6×	0.006	COPB2
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	337.0×	0.006	COPB2
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.010	COPB2
intracellular protein transport	1	64.8×	0.015	COPB2

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
COPB2	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
COPB2	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	COPB2

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)
COPB2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.