PRSS55

Chr 8

serine protease 55

Also known as: CT153, T-SP1, TSP1, UNQ9391

NCBI Gene: 203074 ENSG00000184647 UniProt: Q6UWB4 OMIM: 615144

This gene encodes a membrane-anchored serine protease that is primarily expressed in testicular Leydig and Sertoli cells and plays a crucial role in male fertility including sperm migration and sperm-egg interaction. Mutations in PRSS55 cause autosomal recessive male infertility due to multiple morphological abnormalities of the flagella (MMAF), resulting in severe asthenozoospermia. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with a recessive inheritance pattern where heterozygous carriers are unaffected.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of a group of membrane-anchored chymotrypsin (S1)-like serine proteases. The enocoded protein is primarily expressed in the Leydig and Sertoli cells of the testis and may be involved in male fertility. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.88

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.88LOEUF

pLI 0.000

Z-score -1.04

OE 1.35 (0.88–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-3.40Z-score

OE missense 1.67 (1.53–1.83)

338 obs / 202.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.35 (0.88–1.88)

0≤0.351.4

Missense OE?1.67 (1.53–1.83)

0≤0.61.4

Synonymous OE?1.45

0≤1.21.6

LoF obs/exp: 14 / 10.4Missense obs/exp: 338 / 202.0Syn Z: -3.30

Background carrier burden — how many people carry a rare variant somewhere in PRSS55?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 52

766 rare PASS variants

Rare truncating (LoF)

1 in 930

118 rare PASS variants

Rare synonymous (reference)

1 in 150

297 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRSS55. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 82	1 in 1,000
South Asian	~43k	1 in 55	1 in 410
Remaining (unassigned)	~30k	1 in 54	1 in 790
European (Finnish)	~27k	1 in 160	1 in 2,100
Admixed American	~22k	1 in 56	1 in 1,400
African / African American	~21k	1 in 38	1 in 620
East Asian	~20k	1 in 61	1 in 610
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 55	≈ 1 in 1,300

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓