TMPRSS4

protein-coding

transmembrane serine protease 4, the group of Type II transmembrane serine proteases|Scavenger receptor cysteine rich domain containing

Gene summary

This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular region containing the serine protease domain. The protein has been found to promote SARS-CoV-2 entry into host cells. [provided by RefSeq, Aug 2021]

MANE transcript

NM_019894.4

Inheritance

ClinVar variants

U:70B:9

Top phenotype

autosomal recessive cerebral atrophy

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr11:118,077,012-118,125,510

External References & Databases

Ensembl (ENSG00000137648)

Transcript & Mutation Effects

hg38 • Region Span ~48.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive cerebral atrophySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018218

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMPRSS4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019894.4. 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			1 clinvar			1
missense			63 clinvar	8 clinvar		71
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar	1 clinvar		7
Total	0	0	70	9	0	79

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019894.4	RefSeq	NP_063947.2	13	MANE Select
ENST00000437212.8	Ensembl	ENSP00000416037.3	13	MANE Select
NM_001083947.2	RefSeq	NP_001077416.2	13	Standard
NM_001173551.2	RefSeq	NP_001167022.2	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tmprss4a	Danio rerio	Structure: keratinocyte Quality: detached from abnormal

Gene / Model

Organism

Observed Phenotype

tmprss4a

Danio rerio

Structure: keratinocyte

Quality: detached from

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Influenza A - Homo sapiens (human)
EMT transition in Colorectal Cancer

Biological Process

proteolysis
receptor-mediated endocytosis
response to wounding
regulation of gene expression
negative regulation of growth rate

Molecular Function

serine-type endopeptidase activity
scavenger receptor activity
protein binding

Cellular Component

integral component of membrane
secretory granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000437212
Coding exons: 13
Length: 44853
Individuals with no LoFs: 125666
Homozygous LoFs: 0
Heterozygous LoFs: 81
Defined: 125747
p: 0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.347	242	258	0.939	0.0000142	2866
Missense (PolyPhen)		75	79.205	0.94692		882
Synonymous	0.335	98	102	0.958	0.00000627	829
Loss of Function	1.51	16	24.0	0.668	0.00000111	264

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0024	0.0023	notable
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0.00035	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable protease. Seems to be capable of activating ENaC (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.169

Intolerance Scores

LoFtool: 0.139
RVIS EVS: 1.02
RVIS percentile EVS: 90.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.214

Gene Damage Prediction

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