TASP1

protein-coding

taspase 1

Gene summary

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]

Previous symbols:

C20orf13

MANE transcript

NM_017714.3

Inheritance

ClinVar variants

P:4U:57B:15

Top phenotype

Suleiman-El-Hattab syndrome

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr20:13,389,392-13,638,932

External References & Databases

Ensembl (ENSG00000089123)

Transcript & Mutation Effects

hg38 • Region Span ~249.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Suleiman-El-Hattab syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0033532

Submitter: Ambry Genetics

Suleiman-El-Hattab syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033532

Submitter: PanelApp Australia

Suleiman-El-Hattab syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033532

Submitter: Labcorp Genetics (formerly Invitae)

Suleiman-El-Hattab syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033532

Submitter: G2P

Clinical Genomic Database (CGD)

Suleiman-El-Hattab syndromeAR

Manifestation: Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic

Intervention: Allergy/Immunology/Infectious; Cardiovascular

Rationale: Among other features, individuals have been described with recurrent respiratory infections, and awareness may allow management of these sequelae; The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 31209944

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TASP1 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 38

not specifiedTotal: 16

Suleiman-El-Hattab syndromeTotal: 12

not providedTotal: 11

TASP1-related disorderTotal: 9

Abnormal facial shapeTotal: 1

Happy demeanorTotal: 1

Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017714.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	10 clinvar	2 clinvar	16
missense		1 clinvar	47 clinvar	3 clinvar		51
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)		2 clinvar	5 clinvar			7
Total	1	3	57	13	2	76

Highest pathogenic variant AF is 0.0000020529665

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017714.3	RefSeq	NP_060184.2	13	MANE Select
ENST00000337743.9	Ensembl	ENSP00000338624.4	13	MANE Select
NM_001323602.2	RefSeq	NP_001310531.1	9	Standard
NM_001323603.2	RefSeq	NP_001310532.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
positive regulation of transcription, DNA-templated
protein maturation

Molecular Function

threonine-type endopeptidase activity
hydrolase activity
identical protein binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000337743
Coding exons: 13
Length: 372879
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125742
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.58	159	226	0.704	0.0000114	2689
Missense (PolyPhen)		25	71.404	0.35012		771
Synonymous	-0.133	88	86.4	1.02	0.00000511	827
Loss of Function	3.68	5	24.8	0.202	0.00000124	317

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000066	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000036	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protease involved in KMT2A/MLL1 processing and, consequently, in the correct expression of the early HOXA gene cluster. {ECO:0000269|PubMed:14636557}.;

Recessive Scores

pRec: 0.241

Intolerance Scores

LoFtool: 0.156
RVIS EVS: -0.18
RVIS percentile EVS: 39.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.734

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium