CTSH

protein-coding

cathepsin H, the group of Cathepsins|Minor histocompatibility antigens

Gene summary

The protein encoded by this gene is a lysosomal cysteine proteinase important in the overall degradation of lysosomal proteins. It is composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. The encoded protein, which belongs to the peptidase C1 protein family, can act both as an aminopeptidase and as an endopeptidase. Increased expression of this gene has been correlated with malignant progression of prostate tumors. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

Previous symbols:

CPSB

MANE transcript

NM_004390.5

Inheritance

—

ClinVar variants

U:56B:12

Top phenotype

CTSH-related disorder

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr15:78,921,058-78,949,574

External References & Databases

Ensembl (ENSG00000103811)

Transcript & Mutation Effects

hg38 • Region Span ~28.5 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 CTSH variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 12

CTSH-related disorderTotal: 5

Variant of unknown significanceTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004390.5. 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	5 clinvar	3 clinvar	10
missense			46 clinvar	2 clinvar	1 clinvar	49
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			7 clinvar	1 clinvar		8
Total	0	0	56	8	4	68

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 91 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004390.5	RefSeq	NP_004381.2	12	MANE Select
ENST00000220166.10	Ensembl	ENSP00000220166.6	12	MANE Select
NM_001319137.2	RefSeq	NP_001306066.1	6	Standard
NM_001411095.1	RefSeq	NP_001398024.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Apoptosis - Homo sapiens (human)
Neutrophil degranulation
Surfactant metabolism
Metabolism of proteins

Biological Process

metanephros development
T cell mediated cytotoxicity
adaptive immune response
immune response-regulating signaling pathway
proteolysis

Molecular Function

endopeptidase activity
aminopeptidase activity
cysteine-type endopeptidase activity
serine-type endopeptidase activity
protein binding

Cellular Component

extracellular region
extracellular space
lysosome
cytosol
secretory granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000220166
Coding exons: 12
Length: 28517
Individuals with no LoFs: 125610
Homozygous LoFs: 0
Heterozygous LoFs: 138
Defined: 125748
p: 0.000549

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.535	170	191	0.891	0.0000104	2188
Missense (PolyPhen)		60	78.507	0.76426		893
Synonymous	-0.880	82	72.5	1.13	0.00000438	593
Loss of Function	1.52	16	24.0	0.666	0.00000119	260

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00092	0.00092	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0032	0.0032	notable
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00031	0.00031	rare
South Asian	0.00049	0.00049	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Important for the overall degradation of proteins in lysosomes.;

Recessive Scores

pRec: 0.324

Intolerance Scores

LoFtool: 0.448
RVIS EVS: 0.15
RVIS percentile EVS: 64.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.808

Gene Damage Prediction

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