MPLKIP

Chr 7AR

M-phase specific PLK1 interacting protein

Also known as: ABHS, C7orf11, ORF20, TTD4

NCBI Gene: 136647ENSG00000168303UniProt: Q8TAP9

The protein encoded by this gene localizes to the centrosome during mitosis and to the midbody during cytokinesis. The protein is phosphorylated by cyclin-dependent kinase 1 during mitosis and subsequently interacts with polo-like kinase 1. The protein is thought to function in regulating mitosis and cytokinesis. Mutations in this gene result in nonphotosensitive trichothiodystrophy. [provided by RefSeq, Nov 2009]

Primary Disease Associations & Inheritance

Trichothiodystrophy 4, nonphotosensitiveMIM #234050
AR
208
ClinVar variants
48
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MPLKIP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 95 VUS of 208 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.67LOEUF
pLI 0.000
Z-score 0.28
OE 0.89 (0.48–1.67)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.18Z-score
OE missense 1.05 (0.90–1.23)
106 obs / 101.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.89 (0.48–1.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.90–1.23)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 6 / 6.8Missense obs/exp: 106 / 101.0Syn Z: -0.60

ClinVar Variant Classifications

208 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic7
VUS95
Likely Benign57
Benign7
Conflicting1
41
Pathogenic
7
Likely Pathogenic
95
VUS
57
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
28
1
41
Likely Pathogenic
3
1
3
0
7
VUS
1
81
12
1
95
Likely Benign
1
0
11
45
57
Benign
0
2
5
0
7
Conflicting
—1
Total17845947208

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MPLKIP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MPLKIP-related trichothiodystrophy non-photosensitive

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Trichothiodystrophy 4, nonphotosensitive

MIM #234050

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MPLKIP
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Trichothiodystrophy-associated MPLKIP maintains DBR1 levels for proper lariat debranching and ectodermal differentiation.
Theil AF et al.·EMBO Mol Med
2023
Mitral regurgitation as a phenotypic manifestation of nonphotosensitive trichothiodystrophy due to a splice variant in MPLKIP.
Shah K et al.·BMC Med Genet
2016
A novel MPLKIP-variant in three Finnish patients with non-photosensitive trichothiodystrophy type 4.
Strang-Karlsson S et al.·Am J Med Genet A
2021Case report
Updated strategies for the management, pathogenesis and molecular genetics of different forms of ichthyosis syndromes with prominent hair abnormalities.
Rasheed M et al.·Arch Dermatol Res
2017Review
Development and validation of a prognostic model for cervical cancer by combination of machine learning and high-throughput sequencing.
Shi R et al.·Eur J Surg Oncol
2024Functional
PIBIDS syndrome in two Brazilian siblings.
Abagge KT et al.·BMJ Case Rep
2018Case report
Novel contiguous gene deletion in peruvian girl with Trichothiodystrophy type 4 and glutaric aciduria type 3.
La Serna-Infantes J et al.·Eur J Med Genet
2018Case report
Trichothiodystrophy type 4 in an Indian family.
Pande S et al.·Am J Med Genet A
2020Case report
Bi-allelic TARS Mutations Are Associated with Brittle Hair Phenotype.
Theil AF et al.·Am J Hum Genet
2019
A novel mutation in the C7orf11 gene causes nonphotosensitive trichothiodystrophy in a multiplex highly consanguineous kindred.
Pode-Shakked B et al.·Eur J Med Genet
2015Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools