Seckel syndrome 9

Summary

Seckel syndrome 9 (MONDO:0014767) is a disease caused by TRAIP (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TRAIP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Seckel syndrome 9
Mondo ID	MONDO:0014767
OMIM	616777
DOID	DOID:0070005
UMLS	C4225212
MedGen	907155
GARD	0016158
Is cancer (heuristic)	no

Also known as: SCKL9 · Seckel syndrome 9 · Seckel syndrome caused by mutation in TRAIP · Seckel syndrome type 9 · TRAIP Seckel syndrome

Data availability: 14 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 9

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 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

14 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 3 pathogenic, 2 benign, 2 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
221232	NM_005879.3(TRAIP):c.553C>T (p.Arg185Ter)	TRAIP	Pathogenic	criteria provided, single submitter
221233	NM_005879.3(TRAIP):c.52C>T (p.Arg18Cys)	TRAIP	Pathogenic	no assertion criteria provided
4819264	P47L	TRAIP	Pathogenic	no assertion criteria provided
3067877	NM_005879.3(TRAIP):c.1093C>T (p.Gln365Ter)	TRAIP	Likely pathogenic	criteria provided, single submitter
1032372	NM_005879.3(TRAIP):c.182A>G (p.Lys61Arg)	TRAIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1988898	NM_005879.3(TRAIP):c.989C>T (p.Ser330Phe)	TRAIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
2437226	NM_005879.3(TRAIP):c.868C>A (p.Arg290Ser)	TRAIP	Uncertain significance	criteria provided, single submitter
4080578	NM_005879.3(TRAIP):c.673_677dup (p.Arg226delinsSerTer)	TRAIP	Uncertain significance	criteria provided, single submitter
4291816	NM_005879.3(TRAIP):c.504-15G>A	TRAIP	Uncertain significance	criteria provided, single submitter
587459	NM_005879.3(TRAIP):c.1306C>T (p.Arg436Cys)	TRAIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1098863	NM_005879.3(TRAIP):c.1362A>C (p.Thr454=)	TRAIP	Benign	criteria provided, multiple submitters, no conflicts
1295661	NM_005879.3(TRAIP):c.240+45G>A	TRAIP	Benign	criteria provided, multiple submitters, no conflicts
770702	NM_005879.3(TRAIP):c.303G>A (p.Gln101=)	TRAIP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
777775	NM_005879.3(TRAIP):c.99-9T>G	TRAIP	Benign/Likely 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
TRAIP	Strong	Autosomal recessive	Seckel syndrome 9	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRAIP	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
TRAIP	HGNC:30764	ENSG00000183763	Q9BWF2	E3 ubiquitin-protein ligase TRAIP	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAIP	E3 ubiquitin-protein ligase TRAIP	E3 ubiquitin ligase required to protect genome stability in response to replication stress.

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)
TRAIP	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, TRAIP_ubiq-protein_ligase

Expression context

Cohort genes with no expression data: 0.

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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAIP	169	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRAIP	1,312

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRAIP	Q9BWF2	1

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
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.027	TRAIP

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
protein-DNA covalent cross-linking repair	1	1685.2×	0.004	TRAIP
negative regulation of interferon-beta production	1	1053.2×	0.004	TRAIP
negative regulation of tumor necrosis factor-mediated signaling pathway	1	455.5×	0.005	TRAIP
replication fork processing	1	421.3×	0.005	TRAIP
DNA damage response	1	53.5×	0.030	TRAIP
protein ubiquitination	1	41.4×	0.032	TRAIP
apoptotic process	1	28.7×	0.040	TRAIP
signal transduction	1	16.1×	0.062	TRAIP

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
TRAIP	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	TRAIP

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)
TRAIP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.