SPINT1

Chr 15

serine peptidase inhibitor, Kunitz type 1

Also known as: HAI, HAI1, MANSC2

NCBI Gene: 6692 ENSG00000166145 UniProt: O43278 OMIM: 605123

The protein encoded by this gene is a member of the Kunitz family of serine protease inhibitors. The protein is a potent inhibitor specific for HGF activator and is thought to be involved in the regulation of the proteolytic activation of HGF in injured tissues. Alternative splicing results in multiple variants encoding different isoforms. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.82

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.82LOEUF

pLI 0.000

Z-score 2.24

OE 0.51 (0.32–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.07Z-score

OE missense 0.99 (0.90–1.08)

322 obs / 325.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.32–0.82)

0≤0.351.4

Missense OE?0.99 (0.90–1.08)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 12 / 23.8Missense obs/exp: 322 / 325.7Syn Z: 0.75

Background carrier burden — how many people carry a rare variant somewhere in SPINT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 47

792 rare PASS variants

Rare truncating (LoF)

1 in 1,200

105 rare PASS variants

Rare synonymous (reference)

1 in 130

331 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPINT1. 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 47	1 in 1,300
South Asian	~43k	1 in 49	1 in 790
Remaining (unassigned)	~30k	1 in 44	1 in 1,000
European (Finnish)	~27k	1 in 230	1 in 5,300
Admixed American	~22k	1 in 73	1 in 830
African / African American	~21k	1 in 44	1 in 2,200
East Asian	~20k	1 in 69	1 in 1,800
Ashkenazi Jewish	~13k	1 in 200	none seen
Middle Eastern	~2,884	1 in 46	1 in 470

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 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓