TMPRSS5

protein-coding

transmembrane serine protease 5, the group of Scavenger receptor cysteine rich domain containing|Type II transmembrane serine proteases

Gene summary

This gene encodes a protein that belongs to the serine protease family. Serine proteases are known to be involved in many physiological and pathological processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MANE transcript

NM_030770.4

Inheritance

ClinVar variants

U:74B:26

Top phenotype

TMPRSS5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr11:113,687,547-113,706,373

External References & Databases

Ensembl (ENSG00000166682)

Transcript & Mutation Effects

hg38 • Region Span ~18.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nonsyndromic genetic hearing lossLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019497

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMPRSS5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 83

not providedTotal: 26

TMPRSS5-related disorderTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030770.4. 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	4 clinvar	3 clinvar	9
missense			71 clinvar	16 clinvar	2 clinvar	89
nonsense						0
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	74	20	6	100

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030770.4	RefSeq	NP_110397.2	13	MANE Select
ENST00000299882.11	Ensembl	ENSP00000299882.5	13	MANE Select
NM_001288749.2	RefSeq	NP_001275678.1	9	Standard
NM_001288750.2	RefSeq	NP_001275679.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
receptor-mediated endocytosis

Molecular Function

serine-type endopeptidase activity
scavenger receptor activity
peptidase activity

Cellular Component

plasma membrane
integral component of membrane
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299882
Coding exons: 13
Length: 18824
Individuals with no LoFs: 124554
Homozygous LoFs: 0
Heterozygous LoFs: 86
Defined: 124640
p: 0.000345

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.923	212	253	0.837	0.0000151	2855
Missense (PolyPhen)		58	71.926	0.80639		801
Synonymous	0.619	94	102	0.922	0.00000642	899
Loss of Function	1.37	17	24.3	0.700	0.00000113	262

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00032	rare
Latino/Admixed American	0.00042	0.00041	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00041	0.00039	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00046	0.00044	rare
South Asian	0.000076	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in hearing. {ECO:0000269|PubMed:17918732}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

RVIS EVS: 0.07
RVIS percentile EVS: 59.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.150

Gene Damage Prediction

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