Trichothiodystrophy 5, nonphotosensitive

disease

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Also known as nonphotosensitive trichothiodystrophy caused by mutation in RNF113ARNF113A nonphotosensitive trichothiodystrophyTTD5

Summary

Trichothiodystrophy 5, nonphotosensitive (MONDO:0010495) is a disease caused by RNF113A (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: RNF113A (GenCC Strong)
Cohort genes: 1
ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	trichothiodystrophy 5, nonphotosensitive
Mondo ID	MONDO:0010495
OMIM	300953
DOID	DOID:0111868
UMLS	C4225420
MedGen	899675
GARD	0015277
Is cancer (heuristic)	no

Also known as: nonphotosensitive trichothiodystrophy caused by mutation in RNF113A · RNF113A nonphotosensitive trichothiodystrophy · trichothiodystrophy 5, nonphotosensitive · TTD5

Data availability: 11 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › trichothiodystrophy › trichothiodystrophy 5, nonphotosensitive

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

11 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
872888	NM_006978.3(RNF113A):c.897_898del (p.Cys299_Asp300delinsTer)	RNF113A	Pathogenic	no assertion criteria provided
192382	NM_006978.3(RNF113A):c.901C>T (p.Gln301Ter)	RNF113A	Likely pathogenic	criteria provided, single submitter
2578338	NM_006978.3(RNF113A):c.890_891del (p.Tyr297fs)	RNF113A	Likely pathogenic	criteria provided, single submitter
1312234	NM_006978.3(RNF113A):c.860T>C (p.Leu287Pro)	RNF113A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029122	NM_006978.3(RNF113A):c.76G>A (p.Gly26Arg)	LOC130068621	Uncertain significance	criteria provided, multiple submitters, no conflicts
1029121	NM_006978.3(RNF113A):c.484T>C (p.Tyr162His)	RNF113A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1347333	NM_006978.3(RNF113A):c.242_244del (p.Gly81del)	RNF113A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2417356	NM_006978.3(RNF113A):c.508A>G (p.Met170Val)	RNF113A	Uncertain significance	criteria provided, single submitter
3892295	NM_006978.3(RNF113A):c.468C>G (p.Ile156Met)	RNF113A	Uncertain significance	criteria provided, single submitter
816875	NM_006978.3(RNF113A):c.903_910del (p.Gln302fs)	RNF113A	Uncertain significance	criteria provided, single submitter
1229614	NM_006978.3(RNF113A):c.-11A>G	LOC130068621	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
RNF113A	Strong	X-linked	trichothiodystrophy 5, nonphotosensitive	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF113A	Orphanet:33364	Trichothiodystrophy

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
RNF113A	HGNC:12974	ENSG00000125352	O15541	E3 ubiquitin-protein ligase RNF113A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF113A	E3 ubiquitin-protein ligase RNF113A	Required for pre-mRNA splicing as component of the spliceosome.

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)
RNF113A	Transcription factor	no		Znf_CCCH, Znf_RING, Znf_RING/FYVE/PHD

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
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF113A	240	ubiquitous	marker	granulocyte, leukocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNF113A	2,007

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RNF113A	O15541	11

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
mRNA Splicing - Major Pathway	1	54.6×	0.018	RNF113A

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
snoRNA splicing	1	8426.0×	6e-04	RNF113A
negative regulation of chemokine-mediated signaling pathway	1	2407.4×	0.001	RNF113A
mRNA splicing, via spliceosome	1	91.6×	0.018	RNF113A
DNA repair	1	63.8×	0.020	RNF113A
protein ubiquitination	1	41.4×	0.024	RNF113A

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
RNF113A	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	RNF113A

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)
RNF113A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: RNF113A