TASP1

Chr 20AR

taspase 1

Also known as: C20orf13, SULEHS, dJ585I14.2

NCBI Gene: 55617ENSG00000089123UniProt: Q9H6P5

This gene encodes an endopeptidase that cleaves specific substrates following aspartate residues. The encoded protein undergoes posttranslational autoproteolytic processing to generate alpha and beta subunits, which reassemble into the active alpha2-beta2 heterotetramer. It is required to cleave MLL, a protein required for the maintenance of HOX gene expression, and TFIIA, a basal transcription factor. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Suleiman-El-Hattab syndromeMIM #618950
AR
236
ClinVar variants
27
Pathogenic / LP
0.61
pLI score
0
Active trials
Clinical Summary— TASP1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.61) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 172 VUS of 236 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.42LOEUF
pLI 0.608
Z-score 3.68
OE 0.20 (0.10–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.58Z-score
OE missense 0.70 (0.62–0.80)
159 obs / 225.8 exp
Tolerant

Mild missense constraint

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.0.20 (0.10–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.62–0.80)
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.1.02
0≤1.21.6
LoF obs/exp: 5 / 24.8Missense obs/exp: 159 / 225.8Syn Z: -0.13

ClinVar Variant Classifications

236 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic5
VUS172
Likely Benign25
Benign12
22
Pathogenic
5
Likely Pathogenic
172
VUS
25
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
2
1
2
0
5
VUS
0
152
19
1
172
Likely Benign
0
10
7
8
25
Benign
0
3
7
2
12
Total21665711236

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

View in ClinVar →

Protein Context — Lollipop Plot

TASP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TASP1-related neurodevelopmental disorder

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Suleiman-El-Hattab syndrome

MIM #618950

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Disorders of histone methylation: Molecular basis and clinical syndromes.
Al Ojaimi M et al.·Clin Genet
2022Review
Homozygous loss-of-function variants of TASP1, a gene encoding an activator of the histone methyltransferases KMT2A and KMT2D, cause a syndrome of developmental delay, happy demeanor, distinctive facial features, and congenital anomalies.
Suleiman J et al.·Hum Mutat
2019Case report
Long-term follow-up and novel variant in Suleiman-El-Hattab syndrome: Expanding the genotypic and clinical spectrum of a rare neurodevelopmental disorder.
Sezer A et al.·Eur J Med Genet
2023Natural history
TASP1 is deleted in an infant with developmental delay, microcephaly, distinctive facial features, and multiple congenital anomalies.
Suleiman J et al.·Clin Genet
2018
TASP1 mutation in a female with craniofacial anomalies, anterior segment dysgenesis, congenital immunodeficiency and macrocytic anemia.
Balkin DM et al.·Mol Genet Genomic Med
2019Case report
Novel genetic risk factors influence progression of islet autoimmunity to type 1 diabetes.
Onengut-Gumuscu S et al.·Sci Rep
2020
Regulation of MLL/COMPASS stability through its proteolytic cleavage by taspase1 as a possible approach for clinical therapy of leukemia.
Zhao Z et al.·Genes Dev
2019
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