Microcephaly 24, primary, autosomal recessive

Summary

Microcephaly 24, primary, autosomal recessive (MONDO:0032583) 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 24, primary, autosomal recessive
Mondo ID	MONDO:0032583
OMIM	618179
DOID	DOID:0051035
UMLS	C4748555
MedGen	1648413
GARD	0016302
Is cancer (heuristic)	no

Also known as: MCPH24

Data availability: 6 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 › autosomal genetic disease › autosomal recessive disease › autosomal recessive primary microcephaly › microcephaly 24, 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 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

6 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685995	NM_024057.4(NUP37):c.153_156+3del	NUP37	Pathogenic	criteria provided, single submitter
3775365	NM_024057.4(NUP37):c.354+1G>A	NUP37	Pathogenic	criteria provided, single submitter
807643	NM_024057.4(NUP37):c.225dup (p.Asp76Ter)	NUP37	Pathogenic	criteria provided, single submitter
590329	NM_024057.4(NUP37):c.916C>T (p.Arg306Ter)	NUP37	Likely pathogenic	criteria provided, single submitter
1028291	NM_024057.4(NUP37):c.436G>A (p.Asp146Asn)	NUP37	Uncertain significance	criteria provided, single submitter
3034765	NM_024057.4(NUP37):c.679G>A (p.Val227Ile)	NUP37	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 2 · 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
NUP37	Limited	Autosomal recessive	microcephaly 24, primary, autosomal recessive	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NUP37	Orphanet:2512	Autosomal recessive primary microcephaly
NUP37	Orphanet:656	Hereditary steroid-resistant nephrotic 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
NUP37	HGNC:29929	ENSG00000075188	Q8NFH4	Nucleoporin Nup37	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NUP37	Nucleoporin Nup37	Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC).

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)
NUP37	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS

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
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NUP37	265	ubiquitous	marker	oocyte, secondary oocyte, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NUP37	2,831

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NUP37	Q8NFH4	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. 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
Postmitotic nuclear pore complex (NPC) reformation	1	407.9×	0.007	NUP37
IPs transport between nucleus and cytosol	1	380.7×	0.007	NUP37
IP3 and IP4 transport between cytosol and nucleus	1	380.7×	0.007	NUP37
IP6 and IP7 transport between cytosol and nucleus	1	380.7×	0.007	NUP37
Transport of Ribonucleoproteins into the Host Nucleus	1	356.9×	0.007	NUP37
Regulation of Glucokinase by Glucokinase Regulatory Protein	1	356.9×	0.007	NUP37
Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)	1	356.9×	0.007	NUP37
NEP/NS2 Interacts with the Cellular Export Machinery	1	346.1×	0.007	NUP37
Nuclear import of Rev protein	1	335.9×	0.007	NUP37
Vpr-mediated nuclear import of PICs	1	335.9×	0.007	NUP37
Transport of the SLBP independent Mature mRNA	1	326.3×	0.007	NUP37
SUMOylation of SUMOylation proteins	1	326.3×	0.007	NUP37
Transport of the SLBP Dependant Mature mRNA	1	317.2×	0.007	NUP37
Rev-mediated nuclear export of HIV RNA	1	317.2×	0.007	NUP37
Nuclear Pore Complex (NPC) Disassembly	1	308.6×	0.007	NUP37
SUMOylation of ubiquitinylation proteins	1	292.8×	0.007	NUP37
NS1 Mediated Effects on Host Pathways	1	285.5×	0.007	NUP37
Transport of Mature mRNA Derived from an Intronless Transcript	1	271.9×	0.007	NUP37
Viral Messenger RNA Synthesis	1	259.6×	0.007	NUP37
SUMOylation of DNA replication proteins	1	248.3×	0.007	NUP37
SUMOylation of RNA binding proteins	1	237.9×	0.007	NUP37
snRNP Assembly	1	211.5×	0.008	NUP37
tRNA processing in the nucleus	1	196.9×	0.008	NUP37
SUMOylation of chromatin organization proteins	1	158.6×	0.009	NUP37
Transport of Mature mRNA derived from an Intron-Containing Transcript	1	152.3×	0.009	NUP37
ISG15 antiviral mechanism	1	150.3×	0.009	NUP37
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.009	NUP37
Regulation of HSF1-mediated heat shock response	1	139.3×	0.009	NUP37
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.011	NUP37
HCMV Late Events	1	98.5×	0.013	NUP37

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
nucleocytoplasmic transport	1	391.9×	0.009	NUP37
mRNA transport	1	263.3×	0.009	NUP37
chromosome segregation	1	173.7×	0.010	NUP37
cell division	1	46.2×	0.023	NUP37
protein transport	1	43.9×	0.023	NUP37

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
NUP37	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	NUP37

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)
NUP37	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.