TASP1

Summary

TASP1 (taspase 1, HGNC:15859) is a protein-coding gene on chromosome 20p12.1, encoding Threonine aspartase 1 (Q9H6P5). Protease responsible for KMT2A/MLL1 processing and activation.

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.

Source: NCBI Gene 55617 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Suleiman-El-Hattab syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 99 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 52
• Druggable target: yes
• MANE Select transcript: NM_017714

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15859
Approved symbol	TASP1
Name	taspase 1
Location	20p12.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20212, dJ585I14.2
Ensembl gene	ENSG00000089123
Ensembl biotype	protein_coding
OMIM	608270
Entrez	55617

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000337743, ENST00000434275, ENST00000455532, ENST00000465381, ENST00000476108, ENST00000480436, ENST00000483898, ENST00000861004, ENST00000861005, ENST00000861006, ENST00000861007, ENST00000861008, ENST00000939534, ENST00000939535, ENST00000939536, ENST00000939537, ENST00000961257, ENST00000961258, ENST00000961259, ENST00000961260, ENST00000961261

RefSeq mRNA: 4 — MANE Select: NM_017714 NM_001323602, NM_001323603, NM_001323604, NM_017714

CCDS: CCDS13116

Canonical transcript exons

ENST00000337743 — 14 exons

Exon	Start	End
ENSE00001825059	13638894	13638932
ENSE00003483146	13559008	13559114
ENSE00003486653	13389394	13390452
ENSE00003531748	13417448	13417521
ENSE00003571342	13534022	13534141
ENSE00003579524	13435044	13435154
ENSE00003603153	13625185	13625252
ENSE00003605039	13623446	13623514
ENSE00003615345	13629934	13630152
ENSE00003666283	13587250	13587370
ENSE00003674520	13528433	13528511
ENSE00003675840	13569507	13569586
ENSE00003677352	13580897	13580981
ENSE00003790644	13483227	13483337

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 91.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6090 / max 200.9506, expressed in 1688 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186467	7.1080	1665
186466	0.5010	257

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	91.61	gold quality
tibial artery	UBERON:0007610	91.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.31	gold quality
calcaneal tendon	UBERON:0003701	89.27	gold quality
aorta	UBERON:0000947	89.22	gold quality
secondary oocyte	CL:0000655	88.60	gold quality
epithelium of nasopharynx	UBERON:0001951	87.01	gold quality
descending thoracic aorta	UBERON:0002345	87.00	gold quality
tibia	UBERON:0000979	86.93	gold quality
thoracic aorta	UBERON:0001515	86.32	gold quality
oocyte	CL:0000023	86.29	gold quality
ascending aorta	UBERON:0001496	86.23	gold quality
bronchial epithelial cell	CL:0002328	86.09	gold quality
germinal epithelium of ovary	UBERON:0001304	85.40	gold quality
hair follicle	UBERON:0002073	83.83	gold quality
blood vessel layer	UBERON:0004797	83.54	gold quality
epithelium of bronchus	UBERON:0002031	83.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.07	gold quality
palpebral conjunctiva	UBERON:0001812	82.94	gold quality
bronchus	UBERON:0002185	82.92	gold quality
visceral pleura	UBERON:0002401	82.92	gold quality
left coronary artery	UBERON:0001626	82.36	gold quality
choroid plexus epithelium	UBERON:0003911	82.16	gold quality
tendon	UBERON:0000043	82.15	gold quality
renal glomerulus	UBERON:0000074	82.14	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.07	gold quality
pleura	UBERON:0000977	82.06	gold quality
parietal pleura	UBERON:0002400	81.96	gold quality
metanephric glomerulus	UBERON:0004736	81.71	gold quality
islet of Langerhans	UBERON:0000006	81.41	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.15

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

54 targeting TASP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-5571-5P	99.49	66.99	1764

Literature-anchored findings (GeneRIF, showing 18)

• purification and cloning of threonine aspartase 1 responsible for cleaving MLL; RNAi-mediated knockdown of Taspase1 results in the appearance of unprocessed MLL and the loss of proper HOX gene expression (PMID:14636557)
• Transfected taspase 1 enhances cleavage of TFIIA, and RNA interference knockdown of endogenous taspase 1 diminishes cleavage of TFIIA in vivo. (PMID:16537915)
• TASP1, EPS15R, and PRPF3 expression were significantly induced in HCCs of transgenic EGF2B mice as was P2 promoter-driven HNF4alpha (PMID:18395097)
• Taspase1 is overexpressed in primary human cancers, and deficiency of Taspase1 in cancer cells not only disrupts proliferation but also enhances apoptosis. (PMID:20516119)
• Cell-based analysis of structure-function activity of threonine aspartase 1. (PMID:21084304)
• Taspase1 appears to exploit the nuclear export activity of importin-alpha/nucleophosmin to gain transient access to the cytoplasm required to also cleave its cytoplasmic substrates. (PMID:21418451)
• inefficient heterodimerization appears to be the mechanism by which inactive Taspase1 variants fail to inhibit wild type Taspase1’s activity in trans. (PMID:22570686)
• Our results provide first evidence that Taspase1 processing affects TFIIA regulation of TFIID and suggest that Taspase1 processing of TFIIA is required to establish INR-selective core promoter activity in the presence of NC2. (PMID:25996597)
• simultaneous expression of the leukemogenic AF4-MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4-MLL protein (328 kDa) is subject to proteasomal degradation. (PMID:26137584)
• Studies indicate that threonine Aspartase1 (Taspase1) is overexpressed in numerous liquid and solid malignancies and was characterized as a ’non-oncogene addiction’ protease. (PMID:26657154)
• Taspase 1 processing promotes TFIIA’s nuclear accumulation by evolutionary conserved nuclear export signal (NES, amino acids 21VINDVRDIFL30) masking, and modulates its transcriptional activity. (PMID:28992066)
• Proteolytic processing of TFIIA by Taspase1 was found to mask evolutionary conserved nuclear export signal, thereby promoting nuclear localization and transcriptional activation of TFIIA target genes, such as CDKN2A. (PMID:29097782)
• TASP1 is a novel disease-related gene that is associated with a disease phenotype overlapping with Wiedemann-Steiner syndrome as both are caused by defects in the same pathway. (PMID:29633245)
• TASP1 Promotes Gallbladder Cancer Cell Proliferation and Metastasis by Up-regulating FAM49B via PI3K/AKT Pathway. (PMID:32071545)
• Structural insights into the function of the catalytically active human Taspase1. (PMID:33784495)
• TASP1 Promotes Proliferation and Migration in Gastric Cancer via EMT and AKT/P-AKT Pathway. (PMID:34012990)
• Silencing of circTASP1 inhibits proliferation and induces apoptosis of acute myeloid leukaemia cells through modulating miR-515-5p/HMGA2 axis. (PMID:34197029)
• Taspase1 Facilitates Topoisomerase IIbeta-Mediated DNA Double-Strand Breaks Driving Estrogen-Induced Transcription. (PMID:36766705)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tasp1	ENSDARG00000060580
mus_musculus	Tasp1	ENSMUSG00000039033
rattus_norvegicus	Tasp1	ENSRNOG00000004493
drosophila_melanogaster	Tasp1	FBGN0263602
caenorhabditis_elegans		WBGENE00010480

Paralogs (2): AGA (ENSG00000038002), ASRGL1 (ENSG00000162174)

Protein

Protein identifiers

Threonine aspartase 1 — Q9H6P5 (reviewed: Q9H6P5)

All UniProt accessions (3): Q9H6P5, H7BZ38, Q5JWM4

UniProt curated annotations — full annotation on UniProt →

Function. Protease responsible for KMT2A/MLL1 processing and activation. It also activates KMT2D/MLL2. Through substrate activation, it controls the expression of HOXA genes, and the expression of key cell cycle regulators including CCNA1, CCNB1, CCNE1 and CDKN2A.

Subunit / interactions. Intramolecular proteolysis generates 2 subunits, alpha and beta, which reassemble through a non-covalent association to form the fully active enzyme.

Disease relevance. Suleiman-El-Hattab syndrome (SULEHS) [MIM:618950] An autosomal recessive syndrome characterized by global developmental delay with poor expressive language, poor fine motor skills and hypotonia, microcephaly, feeding difficulties with failure to thrive, recurrent respiratory infections, cardiovascular malformations, cryptorchidism, happy demeanor, and facial dysmorphism. Distinctive facial features are excessive forehead hair, arched and thick eyebrows with synophrys, epicanthus, hypertelorism, thick eyelids with periorbital fullness, broad nasal bridge, long and smooth philtrum, thin upper lip, and low set prominent ears. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Ntn-hydrolase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H6P5-1	1	yes
Q9H6P5-2	2
Q9H6P5-3	3

RefSeq proteins (4): NP_001310531, NP_001310532, NP_001310533, NP_060184* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000246	Peptidase_T2	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR037464	Taspase1	Family

Pfam: PF01112

UniProt features (46 total): strand 15, helix 11, turn 7, splice variant 4, chain 2, mutagenesis site 2, sequence variant 2, sequence conflict 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
2A8J	X-RAY DIFFRACTION	1.9
2A8I	X-RAY DIFFRACTION	2
2A8L	X-RAY DIFFRACTION	2
9D04	X-RAY DIFFRACTION	2.1
6UGK	X-RAY DIFFRACTION	2.15
9D02	X-RAY DIFFRACTION	2.15
9D03	X-RAY DIFFRACTION	2.45
9E6U	X-RAY DIFFRACTION	2.49
2A8M	X-RAY DIFFRACTION	2.6
6VIN	X-RAY DIFFRACTION	3.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6P5-F1	86.41	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 234 (nucleophile)

Mutagenesis-validated functional residues (2):

Position	Phenotype
233	0.1% enzymatic activity; no intramolecular processing.
234	complete loss of enzymatic activity; no intramolecular processing.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 257 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_PROTEIN_MATURATION, MODULE_205, CATTTCA_MIR203, BROWN_MYELOID_CELL_DEVELOPMENT_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, ZHANG_BREAST_CANCER_PROGENITORS_UP, FOXJ2_02, NUYTTEN_EZH2_TARGETS_DN, ZHENG_BOUND_BY_FOXP3, ZHENG_FOXP3_TARGETS_IN_THYMUS_UP, GOBP_PROTEOLYSIS, BLALOCK_ALZHEIMERS_DISEASE_DN, GOMF_PEPTIDASE_ACTIVITY

GO Biological Process (3): proteolysis (GO:0006508), positive regulation of DNA-templated transcription (GO:0045893), protein maturation (GO:0051604)

GO Molecular Function (4): threonine-type endopeptidase activity (GO:0004298), identical protein binding (GO:0042802), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Gene expression (Transcription)	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
cellular anatomical structure	2
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
gene expression	1
endopeptidase activity	1
threonine-type peptidase activity	1
protein binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

844 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TASP1	ASPG	Q86U10	875
TASP1	KMT2A	Q03164	785
TASP1	MLLT1	Q03111	644
TASP1	RBBP5	Q15291	613
TASP1	MEN1	O00255	597
TASP1	HOXA7	P31268	570
TASP1	HOXA9	P31269	566
TASP1	HOXA10	P31260	559
TASP1	GTF2A1	P52655	553
TASP1	GTF2A1L	Q9UNN4	539
TASP1	AFDN	P55196	533
TASP1	ASH2L	Q9UBL3	514
TASP1	HCFC1	P51610	500
TASP1	WDR5	P61964	489
TASP1	AFF1	P51825	479

IntAct

10 interactions, top by confidence:

A	B	Type	Score
TASP1	TASP1	psi-mi:“MI:0407”(direct interaction)	0.650
TASP1	TASP1	psi-mi:“MI:0915”(physical association)	0.650
TASP1		psi-mi:“MI:0194”(cleavage reaction)	0.440
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CUL4A	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): KMT2A (Biochemical Activity), TASP1 (Affinity Capture-RNA), TASP1 (Affinity Capture-MS), TASP1 (Affinity Capture-MS), TASP1 (Affinity Capture-MS), TASP1 (Two-hybrid), TASP1 (Affinity Capture-MS), TASP1 (Affinity Capture-MS), ASRGL1 (Negative Genetic), TASP1 (Affinity Capture-MS), TASP1 (Affinity Capture-MS), TASP1 (Affinity Capture-RNA), HSP90AB1 (Cross-Linking-MS (XL-MS)), TASP1 (Affinity Capture-RNA), APP (Reconstituted Complex)

ESM2 similar proteins: A4FUF0, A4Q9F4, B0K012, E9PTA2, O15315, O35719, O43502, O54804, O54929, O94759, P0C0T1, P42694, Q0V8J1, Q0VGM9, Q3U2J5, Q3ZBL5, Q49A26, Q5BIM1, Q5R7T2, Q5RJZ1, Q5RKH0, Q5ZIA0, Q5ZLS7, Q6DC64, Q6DFV5, Q6IE70, Q6NYU2, Q6P4H8, Q7Z624, Q80VL1, Q86W50, Q8BYN3, Q8CIW5, Q8NHH1, Q8R1C6, Q8R1G1, Q8R2J9, Q8R2Y8, Q91YD4, Q922P9

Diamond homologs: A3MUS8, B3N6Y7, B4GGF2, B4HT15, B4NWI1, B4QHB1, O02467, O57971, P30362, P30364, P37595, P50287, P50288, P74383, Q28Y14, Q29I93, Q32LE5, Q47898, Q4R6C4, Q4R7U8, Q54WW4, Q5BKW9, Q5JHT1, Q6GM78, Q7CQV5, Q7L266, Q8C0M9, Q8GXG1, Q8MR45, Q8R1G1, Q8U4E6, Q8VI04, Q8YQB1, Q9H6P5, Q9V262, Q9VXT7, Q9ZSD6, B3MJ16, B3NN96, B4GHE3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

99 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	52
Likely benign	9
Benign	8

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
633609	NM_017714.3(TASP1):c.199C>T (p.Arg67Ter)	Pathogenic
1878237	NM_017714.3(TASP1):c.675+1G>T	Likely pathogenic
1992428	NM_017714.3(TASP1):c.404-2A>G	Likely pathogenic
633774	NM_017714.3(TASP1):c.701C>T (p.Thr234Met)	Likely pathogenic

SpliceAI

3808 predictions. Top by Δscore:

Variant	Effect	Δscore
20:13394671:T:A	donor_gain	1.0000
20:13417443:CTTA:C	donor_loss	1.0000
20:13417444:TTAC:T	donor_loss	1.0000
20:13417445:TAC:T	donor_loss	1.0000
20:13417446:A:AC	donor_gain	1.0000
20:13417446:A:AG	donor_loss	1.0000
20:13417447:C:CC	donor_gain	1.0000
20:13417447:C:T	donor_loss	1.0000
20:13417517:TTCCA:T	acceptor_gain	1.0000
20:13417518:TCCA:T	acceptor_gain	1.0000
20:13417519:CCA:C	acceptor_gain	1.0000
20:13417519:CCAC:C	acceptor_gain	1.0000
20:13417520:CAC:C	acceptor_gain	1.0000
20:13417521:ACTG:A	acceptor_loss	1.0000
20:13417522:C:A	acceptor_loss	1.0000
20:13417522:C:CC	acceptor_gain	1.0000
20:13417523:T:G	acceptor_loss	1.0000
20:13417525:CCA:C	acceptor_gain	1.0000
20:13417526:C:CT	acceptor_gain	1.0000
20:13417526:C:T	acceptor_gain	1.0000
20:13417527:A:AC	acceptor_gain	1.0000
20:13417527:A:C	acceptor_gain	1.0000
20:13417527:A:T	acceptor_gain	1.0000
20:13435041:TA:T	donor_loss	1.0000
20:13435042:A:AC	donor_gain	1.0000
20:13435043:C:CC	donor_gain	1.0000
20:13435043:C:CG	donor_loss	1.0000
20:13483218:TATAC:T	donor_loss	1.0000
20:13483219:ATACT:A	donor_loss	1.0000
20:13483220:TACTT:T	donor_loss	1.0000

AlphaMissense

2707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:13417479:C:T	G380E	1.000
20:13417480:C:G	G380R	1.000
20:13417480:C:T	G380R	1.000
20:13417482:A:T	V379D	1.000
20:13417504:G:C	H372D	1.000
20:13417510:A:G	W370R	1.000
20:13417510:A:T	W370R	1.000
20:13435115:C:T	G342E	1.000
20:13483331:C:T	G294E	1.000
20:13483337:C:T	G292E	1.000
20:13528440:A:C	S289R	1.000
20:13528440:A:T	S289R	1.000
20:13528442:T:G	S289R	1.000
20:13528447:G:T	A287D	1.000
20:13534031:T:A	R262S	1.000
20:13534031:T:G	R262S	1.000
20:13534032:C:G	R262T	1.000
20:13534059:C:T	G253E	1.000
20:13534061:A:C	S252R	1.000
20:13534061:A:T	S252R	1.000
20:13534062:C:A	S252I	1.000
20:13534063:T:G	S252R	1.000
20:13587261:C:T	G131E	1.000
20:13587299:G:C	S118R	1.000
20:13587299:G:T	S118R	1.000
20:13587301:T:G	S118R	1.000
20:13587304:C:G	A117P	1.000
20:13587348:C:T	G102E	1.000
20:13587352:C:G	A101P	1.000
20:13587353:A:C	N100K	1.000

dbSNP variants (sampled 300 via entrez): RS1000004749 (20:13156326 C>G,T), RS1000007799 (20:13294674 C>G), RS1000014189 (20:13352335 A>G), RS1000015159 (20:13266777 A>C), RS1000015529 (20:13352101 A>G), RS1000017644 (20:13198072 G>A), RS1000019462 (20:13119602 G>A), RS1000021657 (20:13218707 T>C,G), RS1000026967 (20:13129482 C>G), RS1000028423 (20:13216965 G>A), RS1000034738 (20:13384686 C>G,T), RS1000038719 (20:13129675 T>A), RS1000066427 (20:13352631 T>C), RS1000078312 (20:13169906 G>A,T), RS1000083987 (20:13178715 T>C)

Disease associations

OMIM: gene MIM:608270 | disease phenotypes: MIM:618950

GenCC curated gene-disease

Disease	Classification	Inheritance
Suleiman-El-Hattab syndrome	Strong	Autosomal recessive

Mondo (1): Suleiman-El-Hattab syndrome (MONDO:0033532)

Orphanet (0):

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000396	Overfolded helix
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000465	Webbed neck
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000574	Thick eyebrow
HP:0000629	Periorbital fullness
HP:0000646	Amblyopia
HP:0000664	Synophrys
HP:0000954	Single transverse palmar crease

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003518_10	Daytime sleep phenotypes	3.000000e-07
GCST003518_12	Daytime sleep phenotypes	3.000000e-06
GCST003542_186	Night sleep phenotypes	8.000000e-07
GCST003989_22	Chin dimples	6.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6153 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — T2: Glycosylasparaginase precursor

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
yzm18	Inhibition	4.53	pIC50

ChEMBL bioactivities

9 potent at pChembl≥5 of 12 total, top 9 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.82	EC50	1500	nM	CHEMBL4091631
5.66	EC50	2200	nM	CHEMBL4083855
5.48	EC50	3300	nM	CHEMBL4063845
5.41	EC50	3900	nM	CHEMBL4099366
5.40	EC50	4000	nM	CHEMBL3758545
5.38	Ki	4220	nM	CHEMBL1091971
5.23	EC50	5900	nM	CHEMBL4072434
5.12	IC50	7500	nM	CHEMBL1091971
5.00	EC50	9900	nM	CHEMBL4061045

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	4
sodium arsenite	increases abundance, decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
dicrotophos	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	increases reaction, affects binding	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Dactinomycin	increases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Hydrogen Peroxide	decreases expression, increases expression	1
Ozone	affects expression, increases abundance	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1042727	Binding	Inhibition of recombinant Taspase 1 assessed as accumulation of emitted fluorescence by FRET assay	Design, syntheses, and evaluation of Taspase1 inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TR66	HAP1 TASP1 (-) 1	Cancer cell line	Male
CVCL_XU07	HAP1 TASP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.