SPRR1A

Chr 1

small proline rich protein 1A

Also known as: SPRK

NCBI Gene: 6698 ENSG00000169474 UniProt: P35321

A structural constituent of skin epidermis. Involved in cornification and peptide cross-linking. Located in cornified envelope. [provided by Alliance of Genome Resources, Jun 2026]

Research

A structural constituent of skin epidermis. Involved in cornification and peptide cross-linking. Located in cornified envelope. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.87

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.87LOEUF

pLI 0.006

Z-score -0.06

OE 1.04 (0.44–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.69Z-score

OE missense 1.29 (1.04–1.60)

59 obs / 45.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.04 (0.44–1.87)

0≤0.351.4

Missense OE?1.29 (1.04–1.60)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 3 / 2.9Missense obs/exp: 59 / 45.8Syn Z: -0.34

Background carrier burden — how many people carry a rare variant somewhere in SPRR1A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 390

136 rare PASS variants

Rare truncating (LoF)

1 in 4,900

20 rare PASS variants

Rare synonymous (reference)

1 in 1,500

44 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPRR1A. 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 660	1 in 3,500
South Asian	~43k	1 in 520	none seen
Remaining (unassigned)	~30k	1 in 310	1 in 6,000
European (Finnish)	~27k	1 in 1,200	1 in 3,300
Admixed American	~22k	1 in 360	none seen
African / African American	~21k	1 in 330	1 in 1,300
East Asian	~20k	1 in 670	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 6,400	none seen
Middle Eastern	~2,884	1 in 480	none seen

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