SPRR1B

Chr 1

small proline rich protein 1B

Also known as: CORNIFIN, GADD33, SPR-IB, SPRR1

NCBI Gene: 6699 ENSG00000169469 UniProt: P22528 OMIM: 182266

The protein encoded by this gene is an envelope protein of keratinocytes. The encoded protein is crosslinked to membrane proteins by transglutaminase, forming an insoluble layer under the plasma membrane. This protein is proline-rich and contains several tandem amino acid repeats. [provided by RefSeq, Nov 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.93

Clinical Summary— SPRR1B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

18 VUS of 21 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.93LOEUF

pLI 0.001

Z-score -0.76

OE 1.50 (0.64–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.64Z-score

OE missense 1.26 (1.02–1.57)

58 obs / 45.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.50 (0.64–1.93)

0≤0.351.4

Missense OE?1.26 (1.02–1.57)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 4 / 2.7Missense obs/exp: 58 / 45.9Syn Z: -0.57

This gene — mechanism propensity

0.83top 10%

GOF

0.85top 5%

LOF

0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS18

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	18	18
Likely Benign	0	0
Benign	0	0
Total	18	18

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

11 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap SPRR1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →