THOP1

protein-coding

thimet oligopeptidase 1, the group of M3 metallopeptidase family

Gene summary

The protein encoded by this gene is a kininase that uses zinc as a cofactor. The encoded oligopeptidase cleaves cytosolic peptides, making them unavailable for display on antigen-presenting cells. This protein also cleaves neuropeptides under 20 aa in length and can degrade beta-amyloid precursor protein to amyloidogenic peptides. [provided by RefSeq, Nov 2015]

MANE transcript

NM_003249.5

Inheritance

—

ClinVar variants

U:137B:6

Top phenotype

THOP1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr19:2,785,503-2,815,807

External References & Databases

Ensembl (ENSG00000172009)

Transcript & Mutation Effects

hg38 • Region Span ~30.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to THOP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 127

THOP1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003249.5. 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				2 clinvar		2
missense			130 clinvar	4 clinvar		134
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	137	6	0	143

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003249.5	RefSeq	NP_003240.1	13	MANE Select
ENST00000307741.11	Ensembl	ENSP00000304467.5	13	MANE Select
ENST00000395212.8	Ensembl	ENSP00000378638.3	5	Standard
ENST00000585338.1	Ensembl	ENSP00000465545.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Renin-angiotensin system - Homo sapiens (human)
African trypanosomiasis - Homo sapiens (human)

Biological Process

protein polyubiquitination
proteolysis
peptide metabolic process

Molecular Function

metalloendopeptidase activity
peptide binding
metal ion binding

Cellular Component

mitochondrial intermembrane space
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307741
Coding exons: 13
Length: 28142
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125745
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	372	461	0.807	0.0000330	4480
Missense (PolyPhen)		146	209.39	0.69728		2028
Synonymous	-0.713	224	211	1.06	0.0000169	1336
Loss of Function	3.09	12	30.4	0.395	0.00000130	367

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.00020	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000073	0.000070	rare
South Asian	0.000034	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the metabolism of neuropeptides under 20 amino acid residues long. Involved in cytoplasmic peptide degradation. Able to degrade the amyloid-beta precursor protein and generate amyloidogenic fragments.;

Recessive Scores

pRec: 0.174

Intolerance Scores

LoFtool: 0.583
RVIS EVS: -1.48
RVIS percentile EVS: 3.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.935

Gene Damage Prediction

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