Seckel syndrome 10

Summary

Seckel syndrome 10 (MONDO:0014991) is a disease caused by NSMCE2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NSMCE2 (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	Seckel syndrome 10
Mondo ID	MONDO:0014991
OMIM	617253
DOID	DOID:0070008
UMLS	C4310647
MedGen	934614
GARD	0018484
Is cancer (heuristic)	no

Also known as: NSMCE2 Seckel syndrome · SCKL10 · Seckel syndrome 10 · Seckel syndrome caused by mutation in NSMCE2 · Seckel syndrome type 10

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

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Seckel syndrome › Seckel syndrome 10

Related subtypes (11): Seckel syndrome 1, intrauterine growth retardation with increased mitomycin c sensitivity, Seckel syndrome 2, Seckel syndrome 4, Seckel syndrome 5, Seckel syndrome 6, Seckel syndrome 7, Seckel syndrome 8, microcephaly 13, primary, autosomal recessive, Seckel syndrome 9, Seckel syndrome 11

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:

2 uncertain significance, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
372285	NM_173685.4(NSMCE2):c.346del (p.Ser116fs)	NSMCE2	Pathogenic	criteria provided, multiple submitters, no conflicts
372286	NM_173685.4(NSMCE2):c.697_700dup (p.Ala234fs)	NSMCE2	Pathogenic	no assertion criteria provided
3068125	NM_173685.4(NSMCE2):c.265-1G>A	NSMCE2	Likely pathogenic	criteria provided, single submitter
1033207	NM_173685.4(NSMCE2):c.419-18C>T	NSMCE2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1450777	NM_173685.4(NSMCE2):c.577G>A (p.Ala193Thr)	NSMCE2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3600287	NM_173685.4(NSMCE2):c.303ATT[1] (p.Leu103del)	NSMCE2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
NSMCE2	Strong	Autosomal recessive	Seckel syndrome 10	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NSMCE2	Orphanet:436182	Microcephalic primordial dwarfism-insulin resistance syndrome
NSMCE2	Orphanet:808	Seckel 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
NSMCE2	HGNC:26513	ENSG00000156831	Q96MF7	E3 SUMO-protein ligase NSE2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NSMCE2	E3 SUMO-protein ligase NSE2	E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination.

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)
NSMCE2	Transcription factor	no		Znf_MIZ, Znf_RING/FYVE/PHD, Nse2(Mms21)

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
bone marrow cell	1
colonic epithelium	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NSMCE2	259	ubiquitous	marker	colonic epithelium, bone marrow cell, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NSMCE2	1,550

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NSMCE2	Q96MF7	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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 damage response and repair proteins	1	146.4×	0.007	NSMCE2

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
positive regulation of maintenance of mitotic sister chromatid cohesion	1	3370.4×	0.002	NSMCE2
telomere maintenance via recombination	1	1532.0×	0.002	NSMCE2
positive regulation of mitotic metaphase/anaphase transition	1	1203.7×	0.002	NSMCE2
chromatin looping	1	1203.7×	0.002	NSMCE2
regulation of telomere maintenance	1	842.6×	0.002	NSMCE2
protein sumoylation	1	324.1×	0.004	NSMCE2
cellular senescence	1	295.6×	0.004	NSMCE2
double-strand break repair via homologous recombination	1	156.0×	0.007	NSMCE2
cell division	1	46.2×	0.022	NSMCE2

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
NSMCE2	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
NSMCE2	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	NSMCE2

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)
NSMCE2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.