SERPINH1

Chr 11MultiAR

serpin family H member 1

Also known as: AsTP3, CBP1, CBP2, HSP47, OI10, PIG14, PPROM, RA-A47

NCBI Gene: 871 ENSG00000149257 UniProt: P50454 OMIM: 600943

The encoded protein is a collagen-specific molecular chaperone localized to the endoplasmic reticulum that binds specifically to collagen during biosynthesis. Mutations cause osteogenesis imperfecta type X, which follows autosomal recessive inheritance. The gene shows low constraint against loss-of-function variants (pLI = 0.03, LOEUF = 0.75), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The encoded protein is localized to the endoplasmic reticulum and plays a role in collagen biosynthesis as a collagen-specific molecular chaperone. Autoantibodies to the encoded protein have been found in patients with rheumatoid arthritis. Expression of this gene may be a marker for cancer, and nucleotide polymorphisms in this gene may be associated with preterm birth caused by preterm premature rupture of membranes. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, May 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Preterm premature rupture of the membranes, susceptibility to}MIM #610504

Multi

Osteogenesis imperfecta, type XMIM #613848

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Osteogenesis imperfecta, type X; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.75

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.75LOEUF

pLI 0.028

Z-score 2.25

OE 0.35 (0.18–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.05Z-score

OE missense 0.99 (0.90–1.10)

269 obs / 271.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.18–0.75)

0≤0.351.4

Missense OE?0.99 (0.90–1.10)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 5 / 14.1Missense obs/exp: 269 / 271.2Syn Z: -0.78

Background carrier burden — how many people carry a rare variant somewhere in SERPINH1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

586 rare PASS variants

Rare truncating (LoF)

1 in 3,000

64 rare PASS variants

Rare synonymous (reference)

1 in 190

260 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SERPINH1. 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 170	1 in 2,900
South Asian	~43k	1 in 75	1 in 4,800
Remaining (unassigned)	~30k	1 in 98	1 in 5,000
European (Finnish)	~27k	1 in 280	≈ 1 in 8,000
Admixed American	~22k	1 in 93	1 in 4,500
African / African American	~21k	1 in 100	≈ 1 in 4,900
East Asian	~20k	1 in 82	1 in 930
Ashkenazi Jewish	~13k	1 in 330	none seen
Middle Eastern	~2,884	1 in 82	≈ 1 in 2,900

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