Trichothiodystrophy 4, nonphotosensitive
diseaseOn this page
Also known as MPLKIP nonphotosensitive trichothiodystrophynonphotosensitive trichothiodystrophy caused by mutation in MPLKIPPollitt syndromeTTD4
Summary
Trichothiodystrophy 4, nonphotosensitive (MONDO:0021013) is a disease caused by MPLKIP (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: MPLKIP (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 16
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | trichothiodystrophy 4, nonphotosensitive |
| Mondo ID | MONDO:0021013 |
| OMIM | 234050 |
| Orphanet | 75790 |
| DOID | DOID:0050528 |
| NCIT | C146899 |
| SNOMED CT | 403796005 |
| UMLS | C1313961 |
| MedGen | 272036 |
| GARD | 0005271 |
| Is cancer (heuristic) | no |
Also known as: MPLKIP nonphotosensitive trichothiodystrophy · nonphotosensitive trichothiodystrophy caused by mutation in MPLKIP · Pollitt syndrome · trichothiodystrophy 4, nonphotosensitive · TTD4
Data availability: 16 ClinVar variants · 4 GenCC gene-disease records · 4 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › trichothiodystrophy › trichothiodystrophy 4, nonphotosensitive
Related subtypes (6): photosensitive trichothiodystrophy, trichothiodystrophy 5, nonphotosensitive, trichothiodystrophy 6, nonphotosensitive, trichothiodystrophy 8, nonphotosensitive, trichothiodystrophy 9, nonphotosensitive, trichothiodystrophy 7, 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
16 retrieved; paginated sample, class counts are floors:
8 pathogenic, 3 uncertain significance, 2 pathogenic/likely pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1848 | NM_138701.4(MPLKIP):c.148_152del (p.His50fs) | LOC129998295 | Pathogenic | no assertion criteria provided |
| 1332725 | NM_138701.4(MPLKIP):c.229del (p.Arg77fs) | MPLKIP | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1844 | NM_138701.4(MPLKIP):c.430A>G (p.Met144Val) | MPLKIP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1845 | NM_138701.4(MPLKIP):c.137_138del (p.Gly46fs) | MPLKIP | Pathogenic | no assertion criteria provided |
| 1846 | NC_000007.14:g.(40116368_?)_(?_40134601)del | MPLKIP | Pathogenic | no assertion criteria provided |
| 1847 | NM_138701.4(MPLKIP):c.277del (p.Ser93fs) | MPLKIP | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 224867 | NM_138701.4(MPLKIP):c.339+1G>A | MPLKIP | Pathogenic | criteria provided, single submitter |
| 3255600 | NM_138701.4(MPLKIP):c.135C>G (p.Tyr45Ter) | MPLKIP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4528345 | NM_138701.4(MPLKIP):c.339G>A (p.Gln113=) | MPLKIP | Pathogenic | criteria provided, single submitter |
| 4528346 | NM_138701.4(MPLKIP):c.4C>T (p.Gln2Ter) | MPLKIP | Pathogenic | criteria provided, single submitter |
| 3382053 | NM_138701.4(MPLKIP):c.198_199del (p.Pro67fs) | LOC129998295 | Likely pathogenic | criteria provided, single submitter |
| 3242125 | NM_138701.4(MPLKIP):c.397delinsGGA (p.Ser133fs) | MPLKIP | Likely pathogenic | criteria provided, single submitter |
| 1929397 | NM_138701.4(MPLKIP):c.372del (p.Arg126fs) | MPLKIP | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1031149 | NM_138701.4(MPLKIP):c.49G>A (p.Gly17Ser) | MPLKIP | Uncertain significance | criteria provided, single submitter |
| 1953936 | NM_138701.4(MPLKIP):c.377G>A (p.Arg126His) | MPLKIP | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 548559 | NM_138701.4(MPLKIP):c.494G>T (p.Ser165Ile) | MPLKIP | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · 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 |
|---|---|---|---|---|
| MPLKIP | Definitive | Autosomal recessive | trichothiodystrophy 4, nonphotosensitive | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| MPLKIP | 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 |
|---|---|---|---|---|---|
| MPLKIP | HGNC:16002 | ENSG00000168303 | Q8TAP9 | M-phase-specific PLK1-interacting protein | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| MPLKIP | M-phase-specific PLK1-interacting protein | May play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis. |
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) |
|---|---|---|---|---|
| MPLKIP | Other/Unknown | no | MPLKIP-like_vertebrate, TTDN1/SICKLE |
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 |
|---|---|
| kidney epithelium | 1 |
| superior surface of tongue | 1 |
| upper arm skin | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| MPLKIP | 255 | ubiquitous | marker | kidney epithelium, upper arm skin, superior surface of tongue |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MPLKIP | 652 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| MPLKIP | Q8TAP9 | 57.39 |
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 |
|---|---|---|---|---|
| cell division | 1 | 46.2× | 0.022 | MPLKIP |
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 |
|---|---|---|
| MPLKIP | 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 | MPLKIP |
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) |
|---|---|---|
| MPLKIP | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: MPLKIP