Seckel syndrome 7

Summary

Seckel syndrome 7 (MONDO:0013922) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 34
• Phenotypes (HPO): 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000448	Prominent nose	Frequent (30-79%)
HP:0000601	Hypotelorism	Frequent (30-79%)
HP:0000786	Primary amenorrhea	Frequent (30-79%)
HP:0001191	Abnormal carpal morphology	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001385	Hip dysplasia	Frequent (30-79%)
HP:0001513	Obesity	Frequent (30-79%)
HP:0001607	Subglottic stenosis	Frequent (30-79%)
HP:0002750	Delayed skeletal maturation	Frequent (30-79%)
HP:0003067	Madelung deformity	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0004220	Short middle phalanx of the 5th finger	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004626	Lumbar scoliosis	Frequent (30-79%)
HP:0008551	Microtia	Frequent (30-79%)
HP:0008846	Severe intrauterine growth retardation	Frequent (30-79%)
HP:0008850	Severe postnatal growth retardation	Frequent (30-79%)
HP:0009826	Limb undergrowth	Frequent (30-79%)
HP:0010864	Intellectual disability, severe	Frequent (30-79%)
HP:0012814	Bilateral breast hypoplasia	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Seckel syndrome 7
Mondo ID	MONDO:0013922
OMIM	614851
Orphanet	319675
DOID	DOID:0070011
UMLS	C3553870
MedGen	766784
GARD	0017469
Is cancer (heuristic)	no

Also known as: microcephalic primordial dwarfism, Dauber type · NIN Seckel syndrome · SCKL7 · Seckel syndrome 7 · Seckel syndrome caused by mutation in NIN · Seckel syndrome type 7

Data availability: 34 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Seckel syndrome › Seckel syndrome 7

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 8, microcephaly 13, primary, autosomal recessive, Seckel syndrome 9, Seckel syndrome 10, 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

34 retrieved; paginated sample, class counts are floors:

12 benign, 7 uncertain significance, 4 likely pathogenic, 4 conflicting classifications of pathogenicity, 3 pathogenic, 2 benign/likely benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4688327	NM_020921.4(NIN):c.5104dup (p.Ile1702fs)	LOC126861936	Pathogenic	criteria provided, single submitter
211602	NM_020921.4(NIN):c.2482del (p.Arg828fs)	NIN	Pathogenic	criteria provided, single submitter
4525807	NM_020921.4(NIN):c.4100_4103del (p.Asn1367fs)	NIN	Pathogenic	criteria provided, single submitter
2429277	NM_020921.4(NIN):c.1966C>T (p.Gln656Ter)	LOC130055602	Likely pathogenic	criteria provided, single submitter
4845858	NM_020921.4(NIN):c.2290C>T (p.Gln764Ter)	NIN	Likely pathogenic	criteria provided, single submitter
804469	NM_020921.4(NIN):c.6115C>T (p.Arg2039Ter)	NIN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
930474	NM_020921.4(NIN):c.6079-1686G>A	NIN	Likely pathogenic	criteria provided, single submitter
37291	NM_020921.4(NIN):c.5126A>G (p.Asn1709Ser)	LOC126861936	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
790684	NM_020921.4(NIN):c.2041G>A (p.Gly681Arg)	LOC130055602	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2753930	NM_020921.4(NIN):c.2642_2646del (p.Lys881fs)	NIN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
734344	NM_020921.4(NIN):c.5912C>A (p.Pro1971Gln)	NIN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029792	NM_020921.4(NIN):c.3026G>A (p.Ser1009Asn)	NIN	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029793	NM_020921.4(NIN):c.6275C>T (p.Thr2092Ile)	NIN	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434355	NM_020921.4(NIN):c.5781_5784del (p.Ser1927fs)	NIN	Uncertain significance	criteria provided, single submitter
2689583	NM_020921.4(NIN):c.5830G>A (p.Glu1944Lys)	NIN	Uncertain significance	criteria provided, single submitter
3387795	NM_020921.4(NIN):c.3407_3409del (p.Glu1136del)	NIN	Uncertain significance	criteria provided, single submitter
931903	NM_020921.4(NIN):c.5302G>T (p.Val1768Phe)	NIN	Uncertain significance	criteria provided, multiple submitters, no conflicts
931904	NM_020921.4(NIN):c.349G>A (p.Val117Met)	NIN	Uncertain significance	criteria provided, multiple submitters, no conflicts
723723	NM_020921.4(NIN):c.5138T>C (p.Leu1713Pro)	LOC126861936	Likely benign	criteria provided, multiple submitters, no conflicts
129781	NM_020921.4(NIN):c.1974T>C (p.His658=)	LOC130055602	Benign	criteria provided, multiple submitters, no conflicts
1239989	NM_020921.4(NIN):c.1775-26G>C	NIN	Benign	criteria provided, multiple submitters, no conflicts
1250757	NM_020921.4(NIN):c.6192+12C>T	NIN	Benign	criteria provided, multiple submitters, no conflicts
129779	NM_020921.4(NIN):c.1128T>C (p.Val376=)	NIN	Benign	criteria provided, multiple submitters, no conflicts
129780	NM_020921.4(NIN):c.1728G>A (p.Pro576=)	NIN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
129782	NM_020921.4(NIN):c.2616C>A (p.Ala872=)	NIN	Benign	criteria provided, multiple submitters, no conflicts
129787	NM_020921.4(NIN):c.3331C>G (p.Pro1111Ala)	NIN	Benign	criteria provided, multiple submitters, no conflicts
129792	NM_020921.4(NIN):c.4866A>C (p.Glu1622Asp)	NIN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
129796	NM_020921.4(NIN):c.5628+5T>C	NIN	Benign	criteria provided, multiple submitters, no conflicts
129797	NM_020921.4(NIN):c.5637G>A (p.Gln1879=)	NIN	Benign	criteria provided, multiple submitters, no conflicts
129798	NM_020921.4(NIN):c.5800C>G (p.Gln1934Glu)	NIN	Benign	criteria provided, multiple submitters, no conflicts

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
NIN	Limited	Autosomal recessive	Seckel syndrome 7	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NIN	Orphanet:319675	Microcephalic primordial dwarfism, Dauber type
NIN	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
NIN	HGNC:14906	ENSG00000100503	Q8N4C6	Ninein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NIN	Ninein	Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells.

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)
NIN	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair

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
buccal mucosa cell	1
cardiac muscle of right atrium	1
oviduct epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NIN	253	ubiquitous	marker	oviduct epithelium, buccal mucosa cell, cardiac muscle of right atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NIN	2,525

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NIN	Q8N4C6	64.47

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
centrosome-templated microtubule nucleation	1	8426.0×	0.001	NIN
corpus callosum morphogenesis	1	2407.4×	0.001	NIN
corticospinal tract morphogenesis	1	2407.4×	0.001	NIN
microtubule anchoring at centrosome	1	1404.3×	0.001	NIN
centriole-centriole cohesion	1	1296.3×	0.001	NIN
collateral sprouting	1	1203.7×	0.001	NIN
centrosome localization	1	887.0×	0.001	NIN
positive regulation of axonogenesis	1	581.1×	0.002	NIN
intracellular protein localization	1	104.7×	0.010	NIN

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
NIN	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	NIN

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)
NIN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.