SPRR2B

protein-coding

small proline rich protein 2B, the group of Small proline rich proteins

Gene summary

Predicted to be involved in keratinocyte differentiation. Predicted to act upstream of or within response to estradiol. Predicted to be located in cornified envelope and cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001388198.1

Inheritance

—

ClinVar variants

U:11B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr1:153,070,226-153,071,611

External References & Databases

Ensembl (ENSG00000196805)

Transcript & Mutation Effects

hg38 • Region Span ~1.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPRR2B variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001388198.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			11 clinvar	1 clinvar		12
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	11	1	0	12

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001388198.1	RefSeq	NP_001375127.1	1	MANE Select
ENST00000368755.3	Ensembl	ENSP00000357744.1	1	MANE Select
NM_001017418.3	RefSeq	NP_001017418.1	1	Standard
ENST00001096832.1	Ensembl	ENSP00000766638.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology
Formation of the cornified envelope

Biological Process

epidermis development
peptide cross-linking
keratinocyte differentiation
cornification

Molecular Function

structural molecule activity

Cellular Component

cornified envelope
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341611
Coding exons: 1
Length: 71228

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.207	42	38.4	1.09	0.00000180	457
Missense (PolyPhen)
Synonymous	-1.82	25	15.8	1.58	8.92e-7	138
Loss of Function

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.;

Recessive Scores

pRec: 0.0587

Intolerance Scores

LoFtool: 0.724
RVIS EVS: 0.06
RVIS percentile EVS: 58

Essentials

Essential (CRISPR): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium