Microcephaly 11, primary, autosomal recessive

Summary

Microcephaly 11, primary, autosomal recessive (MONDO:0014173) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly 11, primary, autosomal recessive
Mondo ID	MONDO:0014173
OMIM	615414
DOID	DOID:0070287
UMLS	C3809431
MedGen	815761
GARD	0024977
Is cancer (heuristic)	no

Also known as: autosomal recessive primary microcephaly caused by mutation in PHC1 · MCPH11 · microcephaly 11, primary, autosomal recessive · PHC1 autosomal recessive primary microcephaly

Data availability: 10 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 11, 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 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 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

10 retrieved; paginated sample, class counts are floors:

5 benign, 3 uncertain significance, 1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1332797	NM_004426.3(PHC1):c.100C>T (p.Arg34Ter)	PHC1	Pathogenic	criteria provided, single submitter
65406	NM_004426.3(PHC1):c.2974C>T (p.Leu992Phe)	PHC1	Pathogenic/Likely pathogenic	no assertion criteria provided
1031419	NM_004426.3(PHC1):c.1777A>T (p.Met593Leu)	PHC1	Uncertain significance	criteria provided, single submitter
1031420	NM_004426.3(PHC1):c.71C>T (p.Pro24Leu)	PHC1	Uncertain significance	criteria provided, single submitter
211897	NM_004426.3(PHC1):c.2626C>T (p.Arg876Trp)	PHC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1247398	NM_004426.3(PHC1):c.2860+12C>T	PHC1	Benign	criteria provided, multiple submitters, no conflicts
1252581	NM_004426.3(PHC1):c.369C>T (p.Pro123=)	PHC1	Benign	criteria provided, multiple submitters, no conflicts
1271948	NM_004426.3(PHC1):c.93T>A (p.Leu31=)	PHC1	Benign	criteria provided, multiple submitters, no conflicts
1290013	NM_004426.3(PHC1):c.2077A>G (p.Thr693Ala)	PHC1	Benign	criteria provided, multiple submitters, no conflicts
211899	NM_004426.3(PHC1):c.918A>G (p.Arg306=)	PHC1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PHC1	Moderate	Autosomal recessive	microcephaly 11, primary, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PHC1	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
PHC1	HGNC:3182	ENSG00000111752	P78364	Polyhomeotic-like protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PHC1	Polyhomeotic-like protein 1	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PHC1	Transcription factor	no		SAM, Znf_FCS, SAM/pointed_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
adenohypophysis	1
pituitary gland	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHC1	252	ubiquitous	marker	right uterine tube, adenohypophysis, pituitary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PHC1	1,188

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PHC1	P78364	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
SUMOylation of DNA methylation proteins	1	671.8×	0.008	PHC1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.008	PHC1
Transcriptional Regulation by E2F6	1	292.8×	0.008	PHC1
SUMOylation of transcription cofactors	1	243.0×	0.008	PHC1
SUMOylation of RNA binding proteins	1	237.9×	0.008	PHC1
Regulation of PTEN gene transcription	1	178.4×	0.008	PHC1
SUMOylation of chromatin organization proteins	1	158.6×	0.008	PHC1
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.008	PHC1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	146.4×	0.008	PHC1
Oxidative Stress Induced Senescence	1	90.6×	0.011	PHC1

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
cellular response to retinoic acid	1	234.1×	0.013	PHC1
cellular response to leukemia inhibitory factor	1	159.0×	0.013	PHC1
chromatin remodeling	1	73.0×	0.018	PHC1
negative regulation of DNA-templated transcription	1	31.6×	0.032	PHC1

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
PHC1	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	PHC1

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)
PHC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.