Microcephaly 29, primary, autosomal recessive

Summary

Microcephaly 29, primary, autosomal recessive (MONDO:0031060) is a disease caused by PDCD6IP (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PDCD6IP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 29, primary, autosomal recessive
Mondo ID	MONDO:0031060
OMIM	620047
DOID	DOID:0051040
UMLS	C5774220
MedGen	1823993
GARD	0025689
Is cancer (heuristic)	no

Also known as: MCPH29 · microcephaly 29, primary, autosomal recessive

Data availability: 1 ClinVar variant · 2 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 29, 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 24, primary, autosomal recessive, microcephaly 25, primary, autosomal recessive, microcephaly 19, 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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1706482	NM_013374.6(PDCD6IP):c.154_158dup (p.Val54fs)	PDCD6IP	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
PDCD6IP	Strong	Autosomal recessive	microcephaly 29, primary, autosomal recessive	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDCD6IP	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
PDCD6IP	HGNC:8766	ENSG00000170248	Q8WUM4	Programmed cell death 6-interacting protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDCD6IP	Programmed cell death 6-interacting protein	Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity.

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)
PDCD6IP	Other/Unknown	no		BRO1_dom, ALIX_V_dom, BRO1_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
calcaneal tendon	1
nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDCD6IP	295	ubiquitous	marker	calcaneal tendon, nerve, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDCD6IP	2,575

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDCD6IP	Q8WUM4	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Uptake and function of anthrax toxins	1	951.7×	0.003	PDCD6IP
RIPK1-mediated regulated necrosis	1	456.8×	0.003	PDCD6IP
Regulation of necroptotic cell death	1	439.2×	0.003	PDCD6IP
Budding and maturation of HIV virion	1	407.9×	0.003	PDCD6IP
Dengue Virus-Host Interactions	1	45.7×	0.022	PDCD6IP

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
extracellular exosome biogenesis	1	8426.0×	0.001	PDCD6IP
regulation of extracellular exosome assembly	1	5617.3×	0.001	PDCD6IP
actomyosin contractile ring assembly	1	4213.0×	0.001	PDCD6IP
positive regulation of extracellular exosome assembly	1	4213.0×	0.001	PDCD6IP
obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway	1	3370.4×	0.001	PDCD6IP
maintenance of epithelial cell apical/basal polarity	1	2407.4×	0.001	PDCD6IP
regulation of membrane permeability	1	2407.4×	0.001	PDCD6IP
viral budding	1	1872.4×	0.001	PDCD6IP
positive regulation of exosomal secretion	1	1123.5×	0.002	PDCD6IP
viral budding via host ESCRT complex	1	802.5×	0.002	PDCD6IP
regulation of centrosome duplication	1	732.7×	0.002	PDCD6IP
midbody abscission	1	732.7×	0.002	PDCD6IP
multivesicular body assembly	1	526.6×	0.003	PDCD6IP
bicellular tight junction assembly	1	330.4×	0.004	PDCD6IP
mitotic cytokinesis	1	259.3×	0.005	PDCD6IP
macroautophagy	1	240.7×	0.005	PDCD6IP
protein homooligomerization	1	122.1×	0.009	PDCD6IP
protein transport	1	43.9×	0.024	PDCD6IP
apoptotic process	1	28.7×	0.035	PDCD6IP

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
PDCD6IP	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
PDCD6IP	7	Binding:7

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	PDCD6IP

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)
PDCD6IP	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.